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Sample records for highly sensitive uplc-ms

  1. Simple and Sensitive UPLC-MS/MS Method for High-Throughput Analysis of Ibrutinib in Rat Plasma: Optimization by Box-Behnken Experimental Design.

    PubMed

    2016-04-07

    Ibrutinib was the first Bruton's tyrosine kinase inhibitor that was approved by the U.S. Food and Drug Administration (FDA) for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, and waldenstrom macroglobulinemia. The aim of this study was to develop a UPLC-tandem MS method for the high-throughput analysis of ibrutinib in rat plasma samples. A chromatographic condition was optimized by the implementation of the Box-Behnken experimental design. Both ibrutinib and internal standard (vilazodone; IS) were separated within 2 min using the mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in 10 mM ammonium acetate in a ratio of 80+20, eluted at a flow rate of 0.250 mL/min. A simple protein precipitation method was used for the sample cleanup procedure. The detection was performed in electrospray ionization (ESI) positive mode using multiple reaction monitoring by ion transitions of m/z 441.16 > 84.02 for ibrutinib and m/z 442.17 > 155.02 for IS, respectively. All calibration curves were linear in the concentration range of 0.35 to 400 ng/mL (r(2) ≥ 0.997) with a lower LOQ of 0.35 ng/mL only. All validation parameter results were within the acceptance criteria as per international regulatory guidelines. The developed assay was successfully applied in the pharmacokinetic study of a novel ibrutinib self-nanoemulsifying drug-delivery system formulation.

  2. Sensitive UPLC-MS-MS assay for 21 benzodiazepine drugs and metabolites, zolpidem and zopiclone in serum or plasma.

    PubMed

    Marin, Stephanie J; Roberts, Mark; Wood, Michelle; McMillin, Gwendolyn A

    2012-09-01

    This paper reports an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method to quantitate 21 benzodiazepines, zolpidem and zopiclone in serum and plasma. After liquid-liquid extraction, an Acquity UPLC with a TQ Detector and BEH C18 column was used (Waters, Milford, MA). The injection-to-injection run time was 7.5 min. Forty-eight authentic serum and plasma patient specimens were analyzed and results compared to those obtained using a previously published method. Average r(2) values for linearity (1 to 1,000 ng/mL over five days) were all above 0.995, except α-hydroxytriazolam (0.993). Intra-day and inter-day relative standard deviation values were within ± 15% and the percent deviation from the expected concentrations were within ± 11%. Recovery ranged from 62 to 89%. Matrix effects ranged from -28% to +6%. The limits of detection were 1 ng/mL, except for lorazepam, nordiazepam, oxazepam and temazepam (5 ng/mL). Ion ratios were ± 15% for all analytes. For authentic patient specimens (n = 48, 76 positive results), there was excellent correlation between the UPLC-MS-MS results and the previous method. The best least-squares fit had an equation of y = 1.0708x + 1.6521, r(2) = 0.9822. This UPLC-MS-MS method is suitable for the quantification of benzodiazepines and hypnotics in serum and plasma, and offers fast, reliable and sensitive results.

  3. Rapid and Sensitive Determination of Major Active Ingredients and Toxic Components in GinkgoBiloba Leaves Extract (EGb 761) by a Validated UPLC-MS-MS Method.

    PubMed

    Wang, Yao; Liu, Yuan; Wu, Qi; Yao, Xin; Cheng, Zongqi

    2017-01-08

    An accurate, precise and sensitive ultra-performance liquid chromatography tandem mass spectrometric (UPLC-MS-MS) method was developed for the determination of flavonoids, terpene lactones, together with ginkgolic acids in Ginkgo biloba leaves extract (EGb 761). This is the first report of the simultaneous analysis of major active ingredients and toxic components in EGb 761 using UPLC-MS-MS. This analysis afforded good linearity, precision, repeatability and accuracy. In addition, the content of those major bioactive components in EGb 761 prepared by different manufacturers of China was determined to establish the effectiveness of the method. The results indicated that the quantification analysis could be readily utilized as a quality control method for EGb 761 and its other related products using flavonoids, terpene lactones and ginkgolic acids as markers.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    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.

  5. 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

  6. Development of a rapid and sensitive UPLC-MS/MS assay for the determination of TM-2 in beagle dog plasma and its application to a pharmacokinetic study.

    PubMed

    Lin, Hongli; Zhao, Yunli; Men, Lei; Yang, Mingjing; Liu, Hui; Shao, Yanjie; Wang, Pei; Tang, Xing; Yu, Zhiguo

    2015-01-01

    A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 812.39 → 551.35 for TM-2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM-2 (r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively.

  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

    2016-05-04

    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.

  9. SPE-UPLC-MS/MS method for sensitive and rapid determination of aripiprazole in human plasma to support a bioequivalence study.

    PubMed

    Patel, Daxesh P; Sharma, Primal; Sanyal, Mallika; Shrivastav, Pranav S

    2013-04-15

    An improved and rugged UPLC-MS/MS method has been developed and validated for sensitive and rapid determination of aripiprazole in human plasma using aripiprazole-d8 as the internal standard (IS). The analyte and IS were extracted from 100 μL of human plasma by solid-phase extraction using Phenomenex Strata-X (30 mg, 1 cc) cartridges. Chromatography was achieved on an Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) analytical column using methanol: 10mM ammonium formate (85:15, v/v) as the mobile phase with isocratic elution. Quantitation was done using multiple reaction monitoring in the positive ionization mode. The linearity of the method was established in the concentration range 0.05-80 ng/mL. The mean extraction recovery was greater than 96% across QC levels, while intra- and inter batch accuracy and precision (% CV) values ranged from 97.4 to 101.9% and from 1.20 to 3.72% respectively. The relative matrix effect in eight different lots of plasma samples, expressed as % CV for the calculated slopes of calibration curves was 1.08%. The stability of aripiprazole was studied under different storage conditions. The validated method was used to support a bioequivalence study of 10mg aripiprazole formulation in 36 healthy Indian subjects.

  10. 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

    2016-09-05

    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.

  11. 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

    2016-09-05

    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.

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

    PubMed

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

    2015-11-10

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

  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.

  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.

  15. UPLC-MS(E) application in disease biomarker discovery: the discoveries in proteomics to metabolomics.

    PubMed

    Zhao, Ying-Yong; Lin, Rui-Chao

    2014-05-25

    In the last decade, proteomics and metabolomics have contributed substantially to our understanding of different diseases. Proteomics and metabolomics aims to comprehensively identify proteins and metabolites to gain insight into the cellular signaling pathways underlying disease and to discover novel biomarkers for screening, early detection and diagnosis, as well as for determining prognoses and predicting responses to specific treatments. For comprehensive analysis of cellular proteins and metabolites, analytical methods of wider dynamic range higher resolution and good sensitivity are required. Ultra performance liquid chromatography-mass spectrometry(Elevated Energy) (UPLC-MS(E)) is currently one of the most versatile techniques. UPLC-MS(E) is an established technology in proteomics studies and is now expanding into metabolite research. MS(E) was used for simultaneous acquisition of precursor ion information and fragment ion data at low and high collision energy in one analytical run, providing similar information to conventional MS(2). In this review, UPLC-MS(E) application in proteomics and metabolomics was highlighted to assess protein and metabolite changes in different diseases, including cancer, neuropsychiatric pharmacology studies from clinical trials and animal models. In addition, the future prospects for complete proteomics and metabolomics are discussed.

  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.

  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.

  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.

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

    PubMed

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

    2015-11-01

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

  20. Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency.

    PubMed

    Thorsteinsdottir, Margret; Thorsteinsdottir, Unnur A; Eiriksson, Finnur F; Runolfsdottir, Hrafnhildur L; Agustsdottir, Inger M Sch; Oddsdottir, Steinunn; Sigurdsson, Baldur B; Hardarson, Hordur K; Kamble, Nilesh R; Sigurdsson, Snorri Th; Edvardsson, Vidar O; Palsson, Runolfur

    2016-11-15

    Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA. The UPLC-MS/MS assay was optimized by a chemometric approach for absolute quantification of DHA, utilizing isotopically labeled DHA as an internal standard. Experimental screening was conducted with D-optimal design and optimization of the DHA response was performed with central composite face design and related to the peak area of DHA using partial least square regression. Acceptable precision and accuracy of the DHA concentration were obtained over a calibration range of 100 to 5000ng/mL on three different days. The intra- and inter-day accuracy and precision coefficients of variation were well within ±15% for quality control samples analyzed in replicates of six at three concentration levels. Absolute quantification of DHA in urine samples from patients with APRT deficiency was achieved wihtin 6.5min. Measurement of DHA in 24h urine samples from three patients with APRT deficiency, diluted 1:15 (v/v) with 10mM ammonium hydroxide (NH4OH), yielded a concentration of 3021, 5860 and 10563ng/mL and 24h excretion of 816, 1327 and 1649mg, respectively. A rapid and robust UPLC-MS/MS assay for absolute quantification of DHA in urine was successfully developed. We believe this method will greatly facilitate diagnosis and management of patients with APRT deficiency.

  1. Therapeutic monitoring of amphotericin B in Saudi ICU patients using UPLC MS/MS assay.

    PubMed

    Al-Quadeib, Bushra T; Radwan, Mahasen A; Siller, Lidija; Mutch, Elaine; Horrocks, Ben; Wright, Matthew; Alshaer, Abdulaziz

    2014-12-01

    Amphotericin B (AmB) is the first-line agent for the treatment of life-threatening invasive fungal infections. The aim of this study was to monitor AmB in critically ill Saudi patients in ICU after i.v. administration of 0.68 ± 0.1 mg/kg/day Fungizone®. A selective, sensitive and precise UPLC MS/MS method was developed to measure AmB concentrations in these patients. Seven ICU patients with creatinine clearance (ClCr) >40 mL/min were included. AmB levels were analyzed using a Waters Aquity UPLC MS/MS system, a BEH Shield RP18 column and detection via electrospray ionization source with positive ionization mode. The precision and accuracy of the developed UPLC method in the concentration range of 200-4000 ng/mL show no significant difference among inter- and-intra-day analysis (p > 0.05). Linearity was observed over the investigated range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of AmB in these patients, at steady state, showed a high terminal half-life of 124.6 ± 73.4 h, with a highest concentration of 513.9 ± 281.1 ng/mL, a lowest concentration 316.4 ± 129.0 ng/mL and a mean clearance 91.1 ± 39.2 mL/h/kg. The pharmacokinetics of AmB in critically ill Saudi patients in ICU was studied using a fully validated assay. A weak correlation (r = -0.22) of AmB Cl with ClCr was obtained, which suggests the need for further investigation in a larger population.

  2. Folate analysis in foods by UPLC-MS/MS: development and validation of a novel, high throughput quantitative assay; folate levels determined in Australian fortified breads.

    PubMed

    Chandra-Hioe, Maria V; Bucknall, Martin P; Arcot, Jayashree

    2011-08-01

    An ultra-performance liquid chromatography-tandem mass spectrometry method was developed, optimised and validated for the quantification of synthetic folic acid (FA), also called pteroyl-L: -glutamic acid or vitamin B9 and naturally occurring 5-methyltetrahydrofolate (5-MTHF) found in folate-fortified breads. Optimised sample preparation prior to analysis involved addition of (13)C(5) labelled internal standards, treatments with α-amylase and rat serum, solid-phase extraction using aromatic-selective cartridges and ultra-filtration. Analytes were separated on a Waters ACQUITY HSS T3 column during a 6-min run and analysed by positive ion electrospray selected reaction monitoring MS/MS. Standard calibration curves for the two analytes were linear over the range of 0.018-14 μg FA/g of fresh bread (r(2) = 0.997) and 9.3-900 ng 5-MTHF/g of fresh bread (r(2) = 0.999). The absolute recoveries were 90% and 76% for FA and 5-MTHF, respectively. Intra-day coefficients of variation were 3% for FA and 18% for 5-MTHF. The limit of detection was 9.0 ng/g for FA and 4.3 ng/g for 5-MTHF, determined using pre-extracted tapioca starch as the blank matrix. The assay is rugged, fast, accurate and sensitive, applicable to a variety of food matrices and is capable of the detection and quantification of the naturally occurring low levels of 5-MTHF in wheat breads. The findings of this study revealed that the FA range in Australian fortified breads was 79-110 μg/100 g of fresh bread and suggest that the flour may not have the mandated FA fortification level (200-300 μg/100 g of flour), though this cannot be determined conclusively from experimental bread data alone, as variable baking losses have been documented by other authors.

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

    PubMed

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

    2015-02-15

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

  4. Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS.

    PubMed

    Berg, Thomas; Jørgenrud, Benedicte; Strand, Dag Helge

    2013-04-01

    A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample.

  5. Multimycotoxin UPLC-MS/MS for tea, herbal infusions and the derived drinkable products.

    PubMed

    Monbaliu, Sofie; Wu, Aibo; Zhang, Dabing; Van Peteghem, Carlos; De Saeger, Sarah

    2010-12-22

    In recent years the consumption of tea and herbal infusions has increased. These hot drinks are consumed as daily drinks as well as for medicinal purposes. All tea varieties (white, yellow, green, oolong, black and puerh) originate from the leaves of the tea plant, Camellia sinensis. All extracts made of plant or herbal materials which do not contain Camellia sinensis are referred as herbal infusions or tisanes. During processing and manufacturing fungal contamination of the plant materials is possible, enabling contamination of these products with mycotoxins. In this study a multimycotoxin UPLC-MS/MS method was developed and validated for the analysis of the raw tea and herbal infusion materials as well as for their drinkable products. The samples were analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), with a mobile phase consisting of variable mixtures of water and methanol with 0.3% formic acid. The limits of detection for the different mycotoxins varied between 2.1 μg/kg and 121 μg/kg for raw materials and between 0.4 μg/L and 46 μg/L for drinkable products. Afterward 91 different tea and herbal infusion samples were analyzed. Only in one sample, Ceylon melange, 76 μg/kg fumonisin B(1) was detected. No mycotoxins were detected in the drinkable products.

  6. 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

  7. 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.

  8. A Fast One Step Extraction and UPLC-MS/MS Analysis for E2/D2 Series Prostaglandins and Isoprostanes

    PubMed Central

    Brose, Stephen A.; Baker, Andrew G.; Golovko, Mikhail Y.

    2013-01-01

    Prostaglandins (PG) and isoprostanes (iso-PG) may be derived through cyclooxygenase or free radical pathways and are important signaling molecules that are also robust biomarkers of oxidative stress. Their quantification is important for understanding many biological processes where PG, iso-PG, or oxidative stress are involved. One of the common methods for PG and iso-PG quantifications is LC-MS/MS that allows a highly selective, sensitive, simultaneous analysis for prostanoids without derivatization. However, the currently used LC-MS/MS methods require a multi-step extraction and a long (within an hour) LC separation to achieve simultaneous separation and analysis of the major iso-PG. The developed and validated for brain tissue analysis one-step extraction protocol and UPLC-MS/MS method significantly increases the recovery of the PG extraction up to 95%, and allows for a much faster (within 4 min) major iso-PGE2 and -PGD2 separation with 5 times narrower chromatographic peaks as compared to previously used methods. In addition, it decreases the time and cost of analysis due to one-step extraction approach performed in disposable centrifuge tubes. All together, this significantly increases the sensitivity, and the time and cost efficiency of the PG and iso-PG analysis. PMID:23400687

  9. Determination of cannabinoids in whole blood by UPLC-MS-MS.

    PubMed

    Jamey, Carole; Szwarc, Esther; Tracqui, Antoine; Ludes, Bertrand

    2008-06-01

    An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed and validated for the simultaneous determination of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in whole blood. Samples were prepared by protein precipitation followed by solid-phase extraction. Data were acquired using positive electrospray ionization and multiple reaction monitoring. Two transitions were selected for THC (m/z 315.0 > 193.0 and m/z 315.0 > 122.7) and THC-COOH (m/z 345.0 > 299.0 and m/z 345.0 > 327.0), and one transition was chosen for 11-OH-THC (m/z 331.0 > 313.0). Deuterated analogues of each analyte were used as internal standards for quantification. Run time was 10 min. Limits of quantification (LOQ) were 0.05 ng/mL for THC, 0.1 ng/mL for 11-OH-THC, and 0.2 ng/mL for THC-COOH. Linearity was established from LOQ to 50 ng/mL for each substance (r(2) always > 0.999). Accuracy ranged from 96 to 106%, and imprecision was less than 10% for all analytes. The UPLC-MS-MS method was found to be sensitive, specific, and rapid because it requires no derivatization step. It can be an alternative to gas chromatography-mass spectrometry for the determination of cannabinoids in whole blood.

  10. 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.

  11. A novel UPLC-MS/MS method for simultaneous determination of 10 effective constituents in the Jixingshizhen preparation.

    PubMed

    Cui, Kunna; Sun, Shuo; Wang, Ping; Luo, Linda; Yu, Jia; Guo, Xingjie

    2017-04-01

    A novel, reliable and reproducible UPLC-MS/MS method was developed and validated to determine simultaneously the 10 bioactive constituents (baicalin, baicalein, wogonoside, wogonin, luteoloside, dictamnine, fraxinellone, obacunone, geniposidic acid and glycyrrhizic acid) in Jixingshizhen (JXSZ) preparation. Briefly, chromatographic separation was achieved on a Waters BEH C18 column with gradient elution employing a mobile phase composed of acetonitrile and 0.1% formic acid at a flow rate of 0.3 mL/min. All analytes containing internal standard (verapamil) were detected without interference in the multiple reaction monitoring mode with positive electrospray ionization. Further, a comprehensive validation of the method was rigorously executed according to the guidelines of the International Conference on Harmonization and Chinese Pharmacopoeia (2015 Edition). The results indicated that the validated method afforded desired linearity, precision, accuracy, sensitivity and stability. At length, the newly established method was successfully applied to quantify the 10 effective ingredients in JXSZ granules from different production batches, indicating the proposed method in this paper was particularly preferable for the routine analysis of JXSZ preparation as well as the quality control, particularly in situations where high sample throughput and fast analytical speed are required.

  12. A novel, sensitive and selective method of UPLC/MS-MS for rapid simultaneous determination of midodrine and its active metabolite desglymidodrine in human plasma: Application to support bioequivalence study in healthy human volunteers.

    PubMed

    Patel, Daxesh P; Nair, Sneha; Suhagia, Bhanubhai N; Patel, Bhargav M

    2016-11-30

    A specific, rapid, sensitive and selective ultra-performance liquid chromatography - tandem mass spectrometry has been developed for the simultaneous determination of midodrine and desglymidodrine in human plasma. The analytes and its deuterated analogs were quantitatively extracted from 100μL of human plasma by solid phase extraction technique. Separation of analytes was achieved on the Waters Acquity UPLC BEH C18 (50×2.1mm, 1.7μm) column using acetonitrile-4.0mM ammonium formate, pH 2.5(90:10, v/v) as mobile phase. The protonated analytes were quantified by selected reaction monitoring in the positive ionization mode by triple quadrupole mass spectrometer. The calibration plots were linear over the concentration range of 0.050-50.0ng/mL. The intra-batch and inter-batch precision (%CV) across quality control levels was <4.0 and the% mean relative recovery was ≥96%. Various other parameters like stability in different conditions; matrix effect and reproducibility of the method were performed in accordance with the guidelines specified by the USFDA for bioanalytical method development and validation. The developed method was successfully administered to the pharmacokinetics study of 5 mg midodrine tablet in 12 healthy subjects. Reproducibility of assay was proved by reanalysis of 48 incurred samples.

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

    PubMed

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

    2016-03-15

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

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

    PubMed

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

    2015-03-21

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

  15. A rapid UPLC-MS/MS assay for eicosanoids in human plasma: Application to evaluate niacin responsivity.

    PubMed

    Miller, Tricia M; Poloyac, Samuel M; Anderson, Kacey B; Waddell, Brooke L; Messamore, Erik; Yao, Jeffrey K

    2017-01-18

    A rapid and sensitive method using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to simultaneously quantify hydroxyeicosatetraenoic (HETE), dihydroxyeicosatrienoic (DiHETrE), epoxyeicosatrienoic acid (EET), and prostaglandin metabolites of arachidonic acid in human plasma. Sample preparation consisted of solid phase extraction with Oasis HLB (30mg) cartridges for all metabolites. Separation of HETEs, EETs, and DiHETrEs was achieved on an Acquity UPLC BEH C18, 1.7µm (100×2.1mm) reversed-phase column (Waters Corp, Millford, MA) with negative electrospray ionization mass spectrometric detection. A second injection of the same extracted sample allowed for separation and assessment of prostaglandin metabolites under optimized UPLC-MS/MS conditions. Additionally, the endogenous levels of these metabolites in five different matrices were determined in order to select the optimal matrix for assay development. Human serum albumin was shown to have the least amount of endogenous metabolites, a recovery efficiency of 79-100% and a matrix effect of 71 - 100%. Linear calibration curves ranging from 0.416 to 66.67ng/ml were validated. Inter-assay and intra-assay variance was less than 15% at most concentrations. This method was successfully applied to quantify metabolite levels in plasma samples of healthy control subjects receiving niacin administration to evaluate the association between niacin administration and eicosanoid plasma level response.

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

    PubMed

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

    2015-01-01

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

  17. Development and validation of a UPLC-MS/MS method to monitor cephapirin excretion in dairy cows following intramammary infusion.

    PubMed

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

    2014-01-01

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

  18. 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.

  19. 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.

  20. Simultaneous quantification method for comparative pharmacokinetics studies of two major metabolites from geniposide and genipin by online mircrodialysis-UPLC-MS/MS.

    PubMed

    Zhang, Xueju; Liu, Shu; Pi, Zifeng; Liu, Zhiqiang; Song, Fengrui

    2017-01-15

    Genipin-1-o-glucuronic acid and genipin-monosulfate are two major metabolites from geniposide and genipin. Based on diabetic rat model, we developed a simultaneous quantification method to investigate their comparative pharmacokinetics by online mircrodialysis-ultra performance liquid chromatography-mass spectrometry (MD-UPLC-MS/MS) without their standard compounds. Online microdialysis sampling could avoid unexpected contamination or degradation of the analytes during the storage and transfer steps. Combined with good sensitivity, selectivity and selectivity of UPLC-MS/MS, online MD-UPLC-MS/MS method could real-timely monitor metabolites in rat blood for quantitative analysis. Our research found that AUC0→t of genipin-1-o-glucuronic acid and genipin-monosulfate in blood of diabetic group were 17.68 and 7.58 times than those in normal group, respectively, and AUC0→t of genipin-1-o-glucuronic acid was 2.28 times than that of genipin-monosulfate in blood of diabetic group, which revealed the effect of diabetes on the pharmacokinetic properties of the two metabolites. This study not only provides an approach for pharmacokinetic studies for various metabolites from herb medicines, but also can predict druggability of their bioactive metabolites. The insight obtained should facilitate drug development and toxicity research.

  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. Simultaneous UPLC-MS/MS analysis of native catechins and procyanidins and their microbial metabolites in intestinal contents and tissues of male Wistar Furth inbred rats.

    PubMed

    Goodrich, Katheryn M; Neilson, Andrew P

    2014-05-01

    Procyanidins have been extensively investigated for their potential health protective activities. However, the potential bioactivities of procyanidins are limited by their poor bioavailability. The majority of the ingested dose remains unabsorbed and reaches the colon where extensive microbial metabolism occurs. Most existing analytical methods measure either native compounds (catechins and procyanidins), or their microbial metabolites. The objectives of this study were to develop a high-throughput extraction and UPLC-MS/MS method for simultaneous measurement of both native procyanidins and their metabolites, facilitating high-throughput analysis of native and metabolite profiles in various regions of the colon. The present UPLC-MS/MS method facilitates simultaneous resolution and detection of authentic standards of 14 native catechin monomers and procyanidins, as well as 24 microbial metabolites. Detection and resolution of an additional 3 procyanidin dimers and 10 metabolites for which standards were not available was achieved. Elution and adequate resolution of both native compounds and metabolites were achieved within 10min. The intraday repeatability for native compounds was between 1.1 and 16.5%, and the interday repeatability for native compounds was between 2.2 and 25%. Intraday and interday repeatability for metabolites was between 0.6 and 24.1% and 1 and 23.9%, respectively. Observed lower limits of quantification for native compounds were ∼9-350fmol on-column, and for the microbial metabolites were ∼0.8-12,000fmol on-column. Observed lower limits of detection for native compounds were ∼4.5-190fmol on-column, and for metabolites were 0.304-6020fmol on-column. For native monomers and procyanidins, extraction recoveries ranged from 38 to 102%. Extraction recoveries for the 9 microbial metabolites tested ranged from 41 to 95%. Data from tissue analysis of rats gavaged with grape seed extract indicate fairly high accumulation of native compounds

  3. 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...

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

    PubMed

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

    2013-10-15

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

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

    PubMed

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

    2014-01-01

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

  6. Ultrasensitive UPLC-MS/MS method for analysis of etheno-DNA adducts in human white blood cells.

    PubMed

    Li, H; Cui, S; Wang, S; Jiang, X; Zhang, S; Zhang, R; Fu, P P; Sun, X

    2015-01-01

    Etheno-DNA adducts are generated by interaction of cellular DNA with exogenous environmental carcinogens and end products of lipid peroxidation. It has been determined that 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 3,N(4)-etheno-2'-deoxycytidine (εdC) adducts formed in human white blood cells can be used to serve as biomarkers of genetic damage mediated by oxidative stress. In this study, we developed an ultrasensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method used to detect and quantify εdA and dC adducts in human white blood cells. The percent recoveries of εdA and dC adducts were found to be 88.9% ± 2.8 and 95.7% ± 3.7, respectively. The detection limits were ∼ 1.45 fmol for εdA and ∼ 1.27 fmol for εdC in 20 μg of human white blood cell DNA samples, both εdA and εdC adducts could be detected using only ∼ 5 μg of DNA per sample. For validation of the method, 34 human blood cell DNA samples were assayed and the results revealed a significant difference (P < 0.01) between levels (fmol/μg DNA) of 0.82 ± 0.83 (standard deviation [SD]) (range: 0.15-3.11) for εdA, 3.28 ± 3.15 (SD) (range: 0.05-9.6) for εdC in benzene-exposed workers; and 0.04 ± 0.08 (SD) (range: 0.0-0.27) for εdA and 0.77 ± 1.02 (SD) (range: 0.10-4.11) for εdC in non-benzene-exposed workers. Our method shows a high sensitivity and specificity when applied to small amounts of human white blood cell DNA samples; background levels of εdA and εdC could be reproducibly detected. The ultrasensitive and simple detection method is thus suitable for applications in human biomonitoring and molecular epidemiology studies.

  7. 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

  8. Reliable quantification of bisphenol A and its chlorinated derivatives in human urine using UPLC-MS/MS method.

    PubMed

    Venisse, N; Grignon, C; Brunet, B; Thévenot, S; Bacle, A; Migeot, V; Dupuis, A

    2014-07-01

    Bisphenol A (BPA), a widespread man-made chemical classified as an endocrine disruptor, is increasingly considered as a major cause of concern for human health. Chlorine present in drinking water may react with BPA to form chlorinated derivatives (ClxBPA), which have demonstrated a heightened level of estrogenic activity. If many epidemiological studies report that more than 90% of people have detectable BPA levels in their urine, then no such study has been undertaken regarding ClxBPA. The purpose of this work is to propose a highly sensitive and accurate analytical method adapted to large-scale biomonitoring studies aimed at assessing exposure to BPA and ClxBPA through the use of human urine. To achieve this, we have comprehensively validated a method using salting-out assisted liquid/liquid extraction (SALLE) coupled to UPLC-MS/MS and isotope dilution quantification, to measure unconjugated BPA and ClxBPA in human urine according to the accepted guidelines. Deutered BPA as well as deutered 2,2'-DCBPA was used as internal standards. The matrix calibration curve ranged from 0.05 to 1.60 ng mL(-1) and from 0.5 to 16.0 ng mL(-1) for ClxBPA and BPA respectively, and provided good linearity (r²>0.99). This method was precise (the intra- and inter-day coefficients of variation were <20% at three different concentrations: 0.05 ng mL(-1), 0.2 ng mL(-1), 0.8 ng mL(-1) and 0.5 ng mL(-1), 2 ng mL(-1), 8 ng mL(-1) for ClxBPA and BPA, respectively) and accurate (bias ranged from -13% to +12%). The limit of quantification, validated at 0.05 ng mL(-1) and 0.5 ng mL(-1) for ClxBPA and BPA respectively when using 300 µL of urine, was found to be suitable for the concentration existing in real samples. The matrix effect and the BPA cross-contamination were also investigated in this study. The analytical method developed in this study is in accordance with the requirements applicable to biomonitoring of BPA and ClxBPA in human urine.

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

    PubMed

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

    2016-04-01

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

  10. Determination of trimethylamine-N-oxide in combination with L-carnitine and γ-butyrobetaine in human plasma by UPLC/MS/MS.

    PubMed

    Grinberga, Solveiga; Dambrova, Maija; Latkovskis, Gustavs; Strele, Ieva; Konrade, Ilze; Hartmane, Dace; Sevostjanovs, Eduards; Liepinsh, Edgars; Pugovics, Osvalds

    2015-11-01

    An ultra-high-performance liquid chromatography-mass spectrometry (UPLC/MS/MS) method was developed and validated for the quantification of trimethylamine-N-oxide (TMAO) simultaneously with TMAO-related molecules L-carnitine and γ-butyrobetaine (GBB) in human blood plasma. The separation of analytes was achieved using a Hydrophilic interaction liquid chromatography (HILIC)-type column with ammonium acetate-acetonitrile as the mobile phase. TMAO determination was validated according to valid US Food and Drug Administration guidelines. The developed method was successfully applied to plasma samples from healthy volunteers.

  11. 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

    2016-01-05

    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.

  12. 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.

  13. Simultaneous determination of the bioactive components in rat plasma by UPLC-MS/MS and application in pharmacokinetic studies after oral administration of Radix scutellariae extract.

    PubMed

    Tao, Jin-Hua; Xu, Jun; Jiang, Shu; Ling, Yong; Wang, Dong-Geng

    2017-02-16

    A highly sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous quantification of the four main bioactive compounds, i.e., baicalin, baicalein, wogonoside and wogonin in rat plasma after oral administration of Radix scutellariae extract. Clarithromycin was used as an internal standard (IS). Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.4 mL/min, using 0.1% formic acid-acetonitrile as mobile phase. The MS/MS ion transit ions monitored were 447.5 → 270.1 for baicalin, 270.1 → 168.1 for baicalein, 461.2 → 284.0 for wogonoside, 284.2 → 168.1 for wogonin and 748.5 → 158.1 for IS. Method validation was performed according to Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantification (LLOQ) achieved was 1.13 ng/mL for baicalin, 1.23 ng/mL for baicalein, 0.82 ng/mL for wogonoside and 0.36 ng/mL for wogonin, respectively. The calibration curves obtained were linear (r > 0.99) over the concentration range approximately 1-1000 ng/mL. The intra- and inter-day precision was less than 15% and the accuracy was within ±14.7%. After validation, this method was successfully applied to a pharmacokinetic study of Radix scutellariae extract.

  14. 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

    2016-09-05

    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.

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

    PubMed

    Kan, X; Zheng, S-L; Zhou, C-Y

    2014-11-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine phentolamine 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 an isocratic mobile phase system composed of acetonitrile and 1% formic acid in water (33:67, v/v) at a flow rate of 0.45 mL/min. 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 282.1 → 212.0 and m/z 237.1 → 194.2 were used to quantify for phentolamine and carbamazepine (internal standard, IS), respectively. The linearity of this method was found to be within the concentration range of 0.5-100.0 ng/mL with a lower limit of quantification of 0.5 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 60 mg phentolamine to 20 Chinese healthy male volunteers.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. High-throughput and sensitive quantitation of plasma catecholamines by ultraperformance liquid chromatography-tandem mass spectrometry using a solid phase microwell extraction plate.

    PubMed

    Dunand, Marielle; Gubian, Danilo; Stauffer, Maxime; Abid, Karim; Grouzmann, Eric

    2013-04-02

    Plasma catecholamines provide a reliable biomarker of sympathetic activity. The low circulating concentrations of catecholamines and analytical interferences require tedious sample preparation and long chromatographic runs to ensure their accurate quantification by HPLC with electrochemical detection. Published or commercially available methods relying on solid phase extraction technology lack sensitivity or require derivatization of catecholamine by hazardous reagents prior to tandem mass spectrometry (MS) analysis. Here, we manufactured a novel 96-well microplate device specifically designed to extract plasma catecholamines prior to their quantification by a new and highly sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Processing time, which included sample purification on activated aluminum oxide and elution, is less than 1 h per 96-well microplate. The UPLC-MS/MS analysis run time is 2.0 min per sample. This UPLC-MS/MS method does not require a derivatization step, reduces the turnaround time by 10-fold compared to conventional methods used for routine application, and allows catecholamine quantification in reduced plasma sample volumes (50-250 μL, e.g., from children and mice).

  1. Metabolomic Analysis of Diet-Induced Type 2 Diabetes Using UPLC/MS Integrated with Pattern Recognition Approach

    PubMed Central

    Sun, Hui; Zhang, Shuxiang; Zhang, Aihua; Yan, Guangli; Wu, Xiuhong; Han, Ying; Wang, Xijun

    2014-01-01

    Metabolomics represents an emerging discipline concerned with comprehensive assessment of small molecule endogenous metabolites in biological systems and provides a powerful approach insight into the mechanisms of diseases. Type 2 diabetes (T2D), called the burden of the 21st century, is growing with an epidemic rate. However, its precise molecular mechanism has not been comprehensively explored. In this study, we applied urinary metabolomics based on the UPLC/MS integrated with pattern recognition approaches to discover differentiating metabolites, to characterize and explore metabolic pathway disruption in an experimental model for high-fat-diet induced T2D. Six differentiating urinary metabolites were found in the negative mode, and two (2-(4-hydroxy-3-methoxy-phenyl) acetaldehyde sulfate, 2-phenylethanol glucuronide) of which were identified involving the key metabolic pathways linked to pentose and glucuronate interconversions, starch, sucrose metabolism and tyrosine metabolism. Our study provides new insight into pathophysiologic mechanisms and may enhance the understanding of T2D pathogenesis. PMID:24671089

  2. 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.

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

    PubMed

    Kıvrak, İbrahim; Kıvrak, Şeyda; Harmandar, Mansur

    2014-09-01

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

  4. [Characterization and comparison of interferon reference standards using UPLC-MS].

    PubMed

    Tao, Lei; Pei, De-ning; Han, Chun-mei; Chen, Wei; Rao, Chun-ming; Wang, Jun-zhi

    2015-01-01

    The study aims to characterize and compare interferon reference standards from 5 manufacturers. By testing molecular mass and trypsin-digested peptide mass mapping, the amino acid sequence was verified and post-translational modifications such as disulfide bond were identified. Results show that the molecular mass and amino acid sequence were consistent with theory; the disulfide bonds of 4 lots of interferon were Cys1-Cys98/Cys29-Cys138, 1 lot was Cys29-Cys139/Cys86-Cys99; N-terminal "+Met", acetyl N-terminal and Met oxidation were identified in part of the sample. UPLC-MS can be used to characterize and compare interferon reference standards from different manufacturers.

  5. 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...

  6. Simultaneous determination of bioactive components of Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple in rat plasma and tissues by UPLC-MS/MS and its application to pharmacokinetics and tissue distribution.

    PubMed

    Luo, Niancui; Li, Zhenhao; Qian, Dawei; Qian, Yefei; Guo, Jianming; Duan, Jin-Ao; Zhu, Min

    2014-07-15

    A highly sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous quantification of seven components in rat plasma and five components in rat tissues after oral administration of the extracts of different combination Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple and has been applied to compare the different pharmacokinetics and tissue distribution properties of these bioactive components. The extracts of Radix Angelicae Sinensis (RAS), Radix Paeoniae Alba (RPA) and Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple (RRHC) were orally administrated to rats, respectively. The concentrations of ferulic acid, caffeic acid, vanillic acid, ligustilide, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma and the concentrations of ferulic acid, vanillic acid, paeoniflorin, albiflorin and oxypaeoniflorin in tissues were determined by UPLC-MS/MS. The plasma samples were pretreated by protein precipitation with methanol and the tissue samples were homogenated with water and pretreated by protein precipitation with methanol. Chromatographic separation was performed on a C18 column using 0.1% formic acid-acetonitrile as mobile phase for gradient elution. A triple quadrupole (TQ) tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating both in positive and negative ionization mode and operated by multiple-reaction monitoring (MRM) scanning. Noncompartmental pharmacokinetic parameters were calculated by DAS 2.0 program. The differences between each group were compared by SPSS 16.0 with Independent-Samples T-test. The pharmacokinetic parameters (such as Cmax, Tmax, T1/2, AUC0-T, MRT0-T, Vz/F or CLz/F) of all the detected components between the single herb (RAS or RPA) and herb pair (RRHP) showed significant differences (P<0.05). It indicated that the compatibility of RAS and RPA could alter the pharmacokinetics features

  7. 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).

  8. 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

  9. 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.

  10. Automated liquid-liquid extraction based on 96-well plate format in conjunction with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for the quantitation of methoxsalen in human plasma.

    PubMed

    Yadav, Manish; Contractor, Pritesh; Upadhyay, Vivek; Gupta, Ajay; Guttikar, Swati; Singhal, Puran; Goswami, Sailendra; Shrivastav, Pranav S

    2008-09-01

    A sensitive, specific and high throughput bioanalytical method using automated sample processing via 96-well plate liquid-liquid extraction and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of methoxsalen in human plasma. Plasma samples with ketoconazole as internal standard (IS) were prepared by employing 0.2 mL human plasma in ethyl acetate:dichloromethane (80:20, v/v). The chromatographic separation was achieved on a Waters Acquity UPLC BEH C18 column using isocratic mobile phase, consisting of 10 mM ammonium formate and acetonitrile (60:40, v/v), at a flow rate of 0.5 mL/min. The linear dynamic range was established over the concentration range 1.1-213.1 ng/mL for methoxsalen. The method was rugged and rapid with a total run time of 1.5 min. It was successfully applied to a pivotal bioequivalence study in 12 healthy human subjects after oral administration of 10 mg extended release methoxsalen formulation under fasting condition.

  11. Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study.

    PubMed

    Chen, Man-Yun; Tang, Yong-Jun; Wang, Yi-Cheng; Wang, Chong-Zhi; Yuan, Chun-Su; Chen, Yao; Tan, Zhi-Rong; Huang, Wei-Hua; Zhou, Hong-Hao

    2016-05-07

    The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and chronic diseases such as asthma, rheumatoid arthritis and systemic lupus erythematosus. It will be useful and beneficial to validate sensitive method for the determination of BSP, BDP and their metabolites for their pharmacokinetic study. Hereby, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid-liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as internal standard (IS), while solid phase extraction was adopted for sample preparation of BSP using prednisolone as IS. The chromatographic separation was performed on a Hypurity C18 column (150 mm×2.1 mm, 5 μm) for BOH, BDP, B21P and B17P, and a Luna C18 (2) column (150 mm×2.0 mm, 5 μm) for BSP. Electrospray ionization interfaced with positive multiple reaction monitoring (MRM) scan mode was used for mass spectrometric detection. The standard calibration curves were linear within the range of 2.525 × 10(-9)-403.9 × 10(-9) mol·dm(-3) for BSP, 0.125 × 10(-9)-55.81 × 10(-9) mol·dm(-3) for BDP, 0.278 × 10(-9)-74.95 × 10(-9) mol·dm(-3) for BOH, 0.098 × 10(-9)-4.688 × 10(-9) mol·dm(-3) for B17P and 0.226 × 10(-9)-5.411 × 10(-9) mol·dm(-3) for B21P, respectively. The validated method was successfully applied to a bioequivalence study in 23 healthy subjects after they were injected with this compound medicine BSP and BDP.

  12. Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study

    PubMed Central

    Chen, Man-Yun; Tang, Yong-Jun; Wang, Yi-Cheng; Wang, Chong-Zhi; Yuan, Chun-Su; Chen, Yao; Tan, Zhi-Rong; Huang, Wei-Hua; Zhou, Hong-Hao

    2016-01-01

    The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and chronic diseases such as asthma, rheumatoid arthritis and systemic lupus erythematosus. It will be useful and beneficial to validate sensitive method for the determination of BSP, BDP and their metabolites for their pharmacokinetic study. Hereby, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid-liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as internal standard (IS), while solid phase extraction was adopted for sample preparation of BSP using prednisolone as IS. The chromatographic separation was performed on a Hypurity C18 column (150 mm×2.1 mm, 5 μm) for BOH, BDP, B21P and B17P, and a Luna C18 (2) column (150 mm×2.0 mm, 5 μm) for BSP. Electrospray ionization interfaced with positive multiple reaction monitoring (MRM) scan mode was used for mass spectrometric detection. The standard calibration curves were linear within the range of 2.525 × 10−9−403.9 × 10−9 mol·dm−3 for BSP, 0.125 × 10−9−55.81 × 10−9 mol·dm−3 for BDP, 0.278 × 10−9−74.95 × 10−9 mol·dm−3 for BOH, 0.098 × 10−9−4.688 × 10−9 mol·dm−3 for B17P and 0.226 × 10−9−5.411 × 10−9 mol·dm−3 for B21P, respectively. The validated method was successfully applied to a bioequivalence study in 23 healthy subjects after they were injected with this compound medicine BSP and BDP. PMID:27695531

  13. 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).

  14. 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.

  15. UPLC-MS/MS determination of florfenicol and florfenicol amine antimicrobial residues in tilapia muscle.

    PubMed

    Orlando, Eduardo Adilson; Costa Roque, Aline Gabriela; Losekann, Marcos Eliseu; Colnaghi Simionato, Ana Valéria

    2016-11-01

    Despite the benefits to fish farmers, the use of antimicrobials in aquaculture has concerned consumers and competent authorities. The indiscriminate use of such substances promotes the emergence of resistant microorganisms, decreases the effectiveness of treatments, and causes possible toxic effects in humans. In Brazil, florfenicol is the only antimicrobial registered for use in aquaculture and is often used in tilapia in cage creation. Thus, this study aimed to develop a method for determination of florfenicol residues and its metabolite florfenicol amine in tilapia fillet by UPLC-MS/MS. Analytes were extracted with ethyl acetate, followed by liquid-liquid partition clean-up with hexane and SPE. The sorbents C18, phenyl and HLB-Oasis were evaluated by SPE. Phenyl sorbent showed the best results, and the extraction conditions were optimized in the sample matrix with fractional factorial design 2(4-1). The analytes were separated on a C18 chromatographic column (50×2.1mm×1.7μm) using water (A) and acetonitrile (B) as mobile phase at a flow rate of 0.3mLmin(-1) with a linear gradient (in% B): 0-2.0min: 20%; 2.0-2.5min: increase to 90%; 2.5-3.5min: 90%; 3.0-3.5min: decrease to 20%; 4.0-5.0min: 20%. The analytes were monitored in a MS/MS triple quadrupole system by MRM mode with transitions at m/z 356.1>336.1 (florfenicol) and m/z 248.1>130.1 (florfenicol amine). The optimized method was validated obtaining LOQ values of 3 and 25ngg(-1) for florfenicol and florfenicol amine, respectively, precision between 20 and 36%, absolute extraction efficiency between 38 and 80%, and adequate linearity. The method was applied to samples intended for human consumption, and within the 15 evaluated samples, only one showed florfenicol residue at 30ngg(-1), which is below the maximum residue limit established in Brazil.

  16. Partial least-squares-discriminant analysis differentiating Chinese wolfberries by UPLC-MS and flow injection mass spectrometric (FIMS) fingerprints.

    PubMed

    Lu, Weiying; Jiang, Qianqian; Shi, Haiming; Niu, Yuge; Gao, Boyan; Yu, Liangli Lucy

    2014-09-17

    Lycium barbarum L. fruits (Chinese wolfberries) were differentiated for their cultivation locations and the cultivars by ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) and flow injection mass spectrometric (FIMS) fingerprinting techniques combined with chemometrics analyses. The partial least-squares-discriminant analysis (PLS-DA) was applied to the data projection and supervised learning with validation. The samples formed clusters in the projected data. The prediction accuracies by PLS-DA with bootstrapped Latin partition validation were greater than 90% for all models. The chemical profiles of Chinese wolfberries were also obtained. The differentiation techniques might be utilized for Chinese wolfberry authentication.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  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.

  3. Antioxidant properties and UPLC-MS/MS profiling of phenolics in jacquemont's hazelnut kernels (Corylus jacquemontii) and its byproducts from western Himalaya.

    PubMed

    Kumar, Ashish; Kumar, Pawan; Koundal, Rajkesh; Agnihotri, Vijai K

    2016-09-01

    A rapid and selective analytical method was developed to simultaneously quantify seven polyphenolic compounds (gallic acid, catechin, epicatechin, quercetin, kaempferol, syringic acid and p-coumaric acid). 15 phenolics of diverse groups in 80 % ethanolic extracts of jacquemont's hazelnut (Corylus jacquemontii) kernels and its byproducts from western Himalaya using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) were identified. The developed analytical method showed excellent linearity, repeatability and accuracy. Total phenols concentrations were found to be 4446, 1199 and 105 mg gallic acid equivalent (GAE)/Kg of dried extract for jacquemont's hazelnut skin, hard shell and kernels respectively. Antioxidant potential of defatted, raw jacquemont's hazelnut skin, hard shell and kernel extracts assessed by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2'-diphenyl-1-picrylhydrazyl (DPPH) methods were increased in a dose-dependent manner. The IC50 values were observed as 23.12, 51.32, 136.46 and 45.73, 63.65, 169.30 μg/ml for jacquemont's hazelnut skin, hard shell, kernels by DPPH and ABTS assays, respectively. The high phenolic contents in jacquemont's hazelnut skin contributed towards their free radical scavenging capacities.

  4. 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

    2016-09-05

    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.

  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.

  6. Detection and expression analysis of recombinant proteins in plant-derived complex mixtures using nanoUPLC-MS(E).

    PubMed

    Murad, André M; Souza, Gustavo H M F; Garcia, Jerusa S; Rech, Elíbio L

    2011-10-01

    The use of mass spectrometry to identify recombinant proteins that are expressed in total soluble proteins (TSPs) from plant extracts is necessary to accelerate further processing steps. For example, the method consists of TSP sample preparation and trypsin digestion prior to the preliminary characterization using nanoUPLC-MS(E) analysis of the recombinant proteins that are expressed in TSP samples of transgenic soybean seeds. A TSP sample as small as 50 μg can be effectively analyzed. In this study, transgenic soybean seeds that expressed recombinant cancer testis antigen (CTAG) were used. The procedure covered 30% of the protein sequence and was quantified at 0.26 ng, which corresponded to 0.1% of the TSP sample. A comparative proteomic profile was generated by the comparison of a negative control and sample that showed a unique expression pattern of CTAG in a transgenic line. The experimental data from the TSP extraction, sample preparation and data analysis are discussed herein.

  7. 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...

  8. EtG and EtS in Autopsy Blood Samples With and Without Putrefaction Using UPLC-MS-MS.

    PubMed

    Hegstad, Solfrid; Kristoffersen, Lena; Liane, Veronica H; Spigset, Olav

    2017-03-01

    Analytical challenges related to postmortem specimens are well known. The degree of putrefaction of the corpse will influence the quality of the blood samples, and both the efficiency of sample preparation and the subsequent chromatographic performance can be affected. An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed and validated for the determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in postmortem whole blood. Sample preparation prior to UPLC-MS-MS analysis consisted of protein precipitation and filtration through a phospholipid removal plate. Chromatography was achieved using an HSS T3 column and gradient elution with formic acid in water in combination with methanol. The injection volume was 0.5 µL. Negative electrospray ionization was performed in the multiple reaction monitoring mode. Two transitions were monitored for the analytes and one for the internal standards. The between-assay relative standard deviations were in the range of 1.7-7.0% and the limits of quantification were 0.025 and 0.009 mg/L for EtG and EtS, respectively. Recovery was 51-55% and matrix effects ranged from 98% to 106% (corrected with internal standard). Blood samples from nine autopsy cases with various extents of putrefaction were analyzed. The sample preparation efficiently removed the phospholipids from the blood specimens. The samples were clean and the analytical quality of the chromatographic performance was satisfactory for both analytes irrespective of the degree of putrefaction.

  9. 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...

  10. Newborn screening for galactosemia by a second-tier multiplex enzyme assay using UPLC-MS/MS in dried blood spots.

    PubMed

    Ko, Dae-Hyun; Jun, Sun-Hee; Park, Kyoung Un; Song, Sang Hoon; Kim, Jin Q; Song, Junghan

    2011-04-01

    Galactosemia is one of the most important inherited metabolic disorders detected by newborn screening tests. Abnormal results during screening should be confirmed by enzyme activity assays. Recently, we developed a multiplex enzyme assay for galactosemia in erythrocytes using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, we proposed a second-tier multiplex enzyme assay for galactosemia that can be directly applied to dried blood spots (DBSs). Supernatants from two rehydrated-punched 3.2-mm DBSs were incubated with a reaction mixture containing [¹³C6]galactose, [¹³C2]galactose-1-phosphate, and UDP-glucose as substrates for three galactose-metabolizing enzymes. After a 4-hour incubation, the end products from the combined reaction mixture, [¹³C6]galactose-1-phosphate, UDP-[¹³C2]galactose, and UDP-galactose, were simultaneously measured using UPLC-MS/MS. Substrates, products, and internal standards from the mixture of the three enzyme reactions were clearly separated in the UPLC-MS/MS system, with an injection cycle time of 10 min. Intra- and inter-assay imprecisions of the UPLC-MS/MS were 8.4-14.8% and 13.2-15.7% CV, respectively. Enzyme activities in DBSs from 37 normal individuals and 10 patients with enzyme deficiencies were analyzed. DBSs from galactosemia patients showed consistently lower enzyme activities as compared to those of normal individuals. In conclusion, multiplex enzyme assays using UPLC-MS/MS can be successfully applied to DBS analysis. This method allows a fast and effective second-tier test for newborns showing abnormal screening results.

  11. Analysis of 21-hydroxy deflazacort in human plasma by UPLC-MS/MS: application to a bioequivalence study in healthy volunteers.

    PubMed

    Patel, Daxesh P; Sharma, Primal; Patel, Bhargav M; Sanyal, Mallika; Singhal, Puran; Shrivastav, Pranav S

    2013-11-01

    A sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method has been developed for the determination of 21-hydroxy deflazacort in human plasma using betamethasone as the internal standard (IS). After solid-phase extraction from 100 μL human plasma, the analyte and IS were analyzed on Waters Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) column using acetonitrile-4.0mM ammonium formate, pH 3.5 (90:10, v/v) as the mobile phase. The protonated analyte was quantified by selected reaction monitoring in the positive ionization mode by triple quadrupole mass spectrometer. The calibration plots were linear over the concentration range 0.50-500 ng/mL. Intra-batch and inter-batch precision (% CV) and accuracy (%) for five quality control samples ranged within 1.40-4.82% and 98.0-102.0% respectively. The overall mean extraction recovery of 21-hydroxy deflazacort from plasma ranged from 95.3 to 97.3%. Matrix effect was assessed by post-column analyte infusion and the extraction recovery was >95.0% across four quality control levels for the analyte and IS. Stability was evaluated under different conditions like bench top, autosampler, processed sample (at room temperature and in cooling chamber), freeze-thaw and long term stability. The method was applied to support a bioequivalence study of 30 mg deflazacort tablet formulation in 28 healthy subjects. Assay reproducibility was demonstrated by reanalysis of 115 incurred samples.

  12. 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.

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

    PubMed

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

    2015-03-01

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

  14. Rapid quantification of 14 saponins of Maesa lanceolata by UPLC-MS/MS.

    PubMed

    Foubert, K; Cuyckens, F; Vleeschouwer, K; Theunis, M; Vlietinck, A; Pieters, L; Apers, S

    2010-06-15

    Saponins are high molecular weight glycosides which are known for their broad range of biological activities. In case of Maesa lanceolata, a tree growing in African countries, the maesasaponins showed virucidal, haemolytic, molluscicidal and anti-angiogenic activity. Since the different activities are dependent on the structure of the saponins, a method was developed and validated for the analysis of the individual saponins in this plant. Since the saponins were only present in small amounts, it was necessary to develop a very sensitive analytical method. For the fast and sensitive analysis of the extracted and purified plant samples ultra-performance liquid chromatography was coupled to a triple quadrupole mass spectrometer for MS/MS detection. A method in positive ESI mode, using sodium acetate in the mobile phase, was developed. The sodium adduct ion was selected as the precursor ion since it provided better sensitivity and a better, more stable fragmentation compared to the deprotonated and protonated ions. The intensity of the signal obtained by fragmentation of the sodium adducts of the saponins, was optimized by the addition of different concentrations of sodium acetate to the mobile phase. Reference standards were not available for all 14 saponins. Therefore, a relative MS/UV response was calculated allowing the estimation of the saponins in real samples. alpha-Hederin was used as external standard. The method was linear over the investigated concentration range with a good correlation coefficient (>0.99). The intra- and inter-day precisions were below 15% for most maesasaponins with the exception of maesasaponin II, which showed a precision within 20%. The recoveries of the spiked pure compounds maesasaponin IV.1 and VII.1 were 96.6% and 85.5%, respectively. The validated method can be applied in the investigation of the content of 14 saponins in transgenic and non-transgenic plant material of M. lanceolata.

  15. 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.

  16. Development and validation of a systematic UPLC-MS/MS method for simultaneous determination of three phenol impurities in ritonavir.

    PubMed

    Venugopal, N; Vijaya Bhaskar Reddy, A; Madhavi, G

    2014-03-01

    A stability indicating gradient reverse phase UPLC-MS/MS method was developed and validated for the simultaneous determination of three phenol impurities in ritonavir drug substance. The chromatographic separation was performed on Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) using gradient elution of 0.05% ammonia in methanol and 5.0 mM ammonium acetate buffer (30:70, v/v) at a flow rate of 0.2 mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously for the quantification of three phenol impurities. The total run time was 11 min, within which ritonavir and its three impurities were well separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. The calibration curves showed a good linearity over the concentration range of 0.3-1.5 ppm for phenol and 0.1-1.5 ppm for both 4-nitrophenol and N-phenoxycarbonyl-L-valine (NPV). The determination coefficient obtained was >0.9998 in each case. The method had very low limit of detection (LOD) and limit of quantification (LOQ) and the accuracy lies between 97.8% and 103.2% for all the three phenol impurities. The developed method was successfully applied for five formulation batches of ritonavir to determine its phenol impurities.

  17. Global Profiling of Metabolite and Lipid Soluble Microbial Products in Anaerobic Wastewater Reactor Supernatant Using UPLC-MS(E).

    PubMed

    Tipthara, Phornpimon; Kunacheva, Chinagarn; Soh, Yan Ni Annie; Wong, Stephen C C; Pin, Ng Sean; Stuckey, David C; Boehm, Bernhard O

    2017-02-03

    Identification of soluble microbial products (SMPs) released during bacterial metabolism in mixed cultures in bioreactors is essential to understanding fundamental mechanisms of their biological production. SMPs constitute one of the main foulants (together with colloids and bacterial flocs) in membrane bioreactors widely used to treat and ultimately recycle wastewater. More importantly, the composition and origin of potentially toxic, carcinogenic, or mutagenic SMPs in renewable/reused water supplies must be determined and controlled. Certain classes of SMPs have previously been studied by GC-MS, LC-MS, and MALDI-ToF MS; however, a more comprehensive LC-MS-based method for SMP identification is currently lacking. Here we develop a UPLC-MS approach to profile and identify metabolite SMPs in the supernatant of an anaerobic batch bioreactor. The small biomolecules were extracted into two fractions based on their polarity, and separate methods were then used for the polar and nonpolar metabolites in the aqueous and lipid fractions, respectively. SMPs that increased in the supernatant after feed addition were identified primarily as phospholipids, ceramides, with cardiolipins in the highest relative abundance, and these lipids have not been previously reported in wastewater effluent.

  18. Development of an UPLC-MS/MS method for the determination of antibiotic ertapenem on dried blood spots.

    PubMed

    la Marca, Giancarlo; Giocaliere, Elisa; Villanelli, Fabio; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Filippi, Luca; De Gaudio, Marina; De Martino, Maurizio; Galli, Luisa

    2012-03-05

    Ertapenem (Invanz) is a newly developed carbapenem β-lactam antimicrobial agent. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to measure ertapenem concentration during treatment. The analysis was performed by UPLC-MS/MS operating in multiple reaction monitoring (MRM) mode. The calibration curve in matrix was linear in the concentration range of 0.5-100 mg/L with correlation coefficient value higher than 0.997. Performance parameters of this method like lower limit of detection (LLOD, 0.2 mg/L), lower limit of quantification (LLOQ, 0.5 mg/L), matrix effect (20%), intra- and inter-day imprecision (CV within than 15%) and accuracy (between 94 and 155%) of drug concentrations have been evaluated. The drug stability at different temperatures was tested for one month, to evaluate the risks of sample delivery at different climatic conditions. The reported method allows now ertapenem analysis and offers many advantages for patients including the possibility of collecting samples at home. This new assay is both precise and accurate and is especially suitable for therapeutic drug monitoring and pharmacokinetic studies in neonates in whom obtaining larger blood samples is not convenient or possible.

  19. Determination of ω-6 and ω-3 PUFA metabolites in human urine samples using UPLC/MS/MS.

    PubMed

    Sasaki, Ai; Fukuda, Hayato; Shiida, Narumi; Tanaka, Nobuaki; Furugen, Ayako; Ogura, Jiro; Shuto, Satoshi; Mano, Nariyasu; Yamaguchi, Hiroaki

    2015-02-01

    The ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are the precursors of various bioactive lipid mediators including prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acid, isoprostanes, lipoxins, and resolvins (Rvs). These lipid mediators play important roles in various physiological and pathological processes. The quantitative determination of PUFA metabolites seems necessary for disease research and for developing biomarkers. However, there is a paucity of analytical methods for the quantification of ω-6 and ω-3 PUFA metabolites—the specialized pro-resolving mediators (SPMs) present in the human urine. We developed a method for the quantification of ω-6 and ω-3 PUFA metabolites present in human urine using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS). The developed method shows good linearity, with a correlation coefficient >0.99 for all of the analytes. The validation results indicate that our method is adequately reliable, accurate, and precise. The method was successfully used to examine urine samples obtained from 43 healthy volunteers. We could identify 20 PUFA metabolites, and this is the first report of the quantitative determination of RvD1, 17(R)-RvD1, 11-dehydro thromboxane B3, RvE2, and 5(S)-HETE in human urine. The urinary 8-iso PGF(2α) and PGE2 levels were significantly higher in the men smokers than in the men nonsmokers (p < 0.05). In this study, we developed an accurate, precise, and novel analytical method for estimating the ω-6 and ω-3 PUFA metabolites, and this is the first report that the SPMs derived from EPA and DHA are present in human urine.

  20. A validated UPLC-MS/MS method for the surveillance of ten aquatic biotoxins in European brackish and freshwater systems.

    PubMed

    Greer, Brett; McNamee, Sara E; Boots, Bas; Cimarelli, Lucia; Guillebault, Delphine; Helmi, Karim; Marcheggiani, Stefania; Panaiotov, Stefan; Breitenbach, Ulrich; Akçaalan, Reyhan; Medlin, Linda K; Kittler, Katrin; Elliott, Christopher T; Campbell, Katrina

    2016-05-01

    Over the past few decades, there has been an increased frequency and duration of cyanobacterial Harmful Algal Blooms (HABs) in freshwater systems globally. These can produce secondary metabolites called cyanotoxins, many of which are hepatotoxins, raising concerns about repeated exposure through ingestion of contaminated drinking water or food or through recreational activities such as bathing/swimming. An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) multi-toxin method has been developed and validated for freshwater cyanotoxins; microcystins-LR, -YR, -RR, -LA, -LY and -LF, nodularin, cylindrospermopsin, anatoxin-a and the marine diatom toxin domoic acid. Separation was achieved in around 9min and dual SPE was incorporated providing detection limits of between 0.3 and 5.6ng/L of original sample. Intra- and inter-day precision analysis showed relative standard deviations (RSD) of 1.2-9.6% and 1.3-12.0% respectively. The method was applied to the analysis of aquatic samples (n=206) from six European countries. The main class detected were the hepatotoxins; microcystin-YR (n=22), cylindrospermopsin (n=25), microcystin-RR (n=17), microcystin-LR (n=12), microcystin-LY (n=1), microcystin-LF (n=1) and nodularin (n=5). For microcystins, the levels detected ranged from 0.001 to 1.51μg/L, with two samples showing combined levels above the guideline set by the WHO of 1μg/L for microcystin-LR. Several samples presented with multiple toxins indicating the potential for synergistic effects and possibly enhanced toxicity. This is the first published pan European survey of freshwater bodies for multiple biotoxins, including two identified for the first time; cylindrospermopsin in Ireland and nodularin in Germany, presenting further incentives for improved monitoring and development of strategies to mitigate human exposure.

  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 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.

  3. Screening of lignan patterns in Schisandra species using ultrasonic assisted temperature switch ionic liquid microextraction followed by UPLC-MS/MS analysis.

    PubMed

    Dong, Wei; Yu, Shuijing; Deng, Yangwu; Pan, Tao

    2016-01-01

    The ultrasonic assisted temperature-switch ionic liquid microextraction (UATS-ILME) has been successfully applied in extracting of seven lignans from Schisandra. 1-Butyl-3-methylimidazolium tetrafluoroborate ([C4MIM][BF4]) aqueous solution was selected for extracting the target analytes in raw material at 80°C. The lignans were deposited into a single drop by in situ forming 1-butyl-3-methylimidazolium hexafluorophosphate ([C4MIM][PF6]) by cooling down to 0°C and centrifuging for 10min. The extracts were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) in a robust multiple-reaction monitoring (MRM) mode in five minutes. Meanwhile, the proposed method was validated and successfully applied to the determination of seven lignans in twelve Schisandra species. The results indicated that UATS-ILME combined with UPLC-MS/MS is a powerful and practical tool, which has great potential for comprehensive quality control of herbal medicines.

  4. 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.

  5. Pharmacokinetic properties of isorhamnetin, kaempferol and quercetin after oral gavage of total flavones of Hippophae rhamnoides L. in rats using a UPLC-MS method.

    PubMed

    Li, Guowen; Zeng, Xiaoli; Xie, Yan; Cai, Zhenzhen; Moore, Jeffrey C; Yuan, Xiurong; Cheng, Zhihong; Ji, Guang

    2012-01-01

    An ultra performance liquid chromatography-mass spectrometric (UPLC-MS) method was developed to investigate the pharmacokinetic properties of isorhamnetin, kaempferol and quercetin from a total flavone extract of Hippophae rhamnoides L. (TFH) after single dose oral administration. Rat plasma samples were pretreated using liquid-liquid extraction, and chromatographic separation was performed on a C(18) column using a linear gradient of methanol and formic acid (0.1%). The pharmacokinetic parameters of isorhamnetin, kaempferol and quercetin from TFH in rats were quantitatively determined by UPLC with photodiode array detection (PDA). The qualitative detection of the three flavones was accomplished by selected ion monitoring in negative ion mode ESI-MS. Results of the pharmacokinetic study indicate that the three flavones in TFH were absorbed by passive diffusion in rats, and no "double-peak" phenomenon was observed in C-t curves of the three flavones from TFH except for quercetin. Results of this study indicate that the pharmacokinetic behaviors of isorhamnetin, kaempferol and quercetin when administered together in a complex herbal extract might be different than the individual behaviors of the same compounds administered in their pure forms. Results of this study also demonstrate that UPLC-MS is a rapid and practical method to determine the pharmacokinetic parameters of flavones present in an herbal extract.

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

    PubMed

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

    2015-10-10

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

  7. Rapid determination of alkaloids in Macleaya cordata using ionic liquid extraction followed by multiple reaction monitoring UPLC-MS/MS analysis.

    PubMed

    Li, Linqiu; Huang, Mingyuan; Shao, Junli; Lin, Bokun; Shen, Qing

    2017-02-20

    The ultrasonic-assisted extraction (UAE) and ionic liquid based dispersive liquid-liquid microextraction (IL-DLLME) have been successfully applied in extracting of six alkaloids from M. cordata. 1-hexyl-3-methylimidazolium tetrafluoroborate ([C6MIM][BF4]) aqueous solution was used as extraction solvent. The target analytes in raw material were deposited into a single drop of 1-hexyl-3-methylimidazolium hexafluorophosphate ([C6MIM][PF6]), which was in situ formed by mixing [C6MIM][BF4] and potassium hexafluorophosphate ([K][PF6]. Afterwards, the extract was analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) in multiple-reaction monitoring (MRM) mode. The proposed method was fully validated in terms of linearity (0.9983-0.9992), LOD (0.080ngmL(-1)), LOQ (0.25ngmL(-1)), intra-day precision (<5.46%), inter-day precision (<6.36%), and recovery (86.42-112.48%). The results indicate that the approach of combining IL-DLLME with UPLC-MS/MS is powerful and practical for analyzing alkaloids in M. cordata., and it also has great potential for comprehensive quality control of other herbal medicines.

  8. UPLC-MS/MS Determination of Deuterated 25-Hydroxyvitamin D (d3-25OHD3) and Other Vitamin D Metabolites for the Measurement of 25OHD Half-Life.

    PubMed

    Assar, Shima; Schoenmakers, Inez; Koulman, Albert; Prentice, Ann; Jones, Kerry S

    2017-01-01

    Plasma 25-hydroxyvitamin D (25OHD) half-life (25OHDt 1/2) is a dynamic marker of vitamin D metabolism that can be used to assess vitamin D expenditure and help inform vitamin D requirements. Our group recently established an approach to determine the 25OHDt 1/2 as an alternative biomarker of 25OHD expenditure in humans. The approach uses a small oral dose of stable isotope labeled 25OHD3 [3-(2)H-25OHD(3) (6,19,19-d3)] (d3-25OHD3) (tracer), which is distinguishable from endogenous 25OHD by liquid chromatography tandem-mass spectrometry (LC-MS/MS). We report here the method, which relies on protein precipitation, purification with solid phase extraction, derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), and determination of the compounds by isotope-dilution UPLC-MS/MS. The method proved to be rapid and sensitive (LOQ 0.2 nmol/L) for the quantification of this tracer as well as the other vitamin D metabolites: 25OHD3, 25OHD2, and 24,25(OH)2D3 in human plasma.

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2015-01-01

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

  11. Simultaneous determination of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I in Beagle dogs plasma by UPLC-MS/MS and its application to a pharmacokinetic study after Oral Administration of Shaofu Zhuyu Decoction.

    PubMed

    Huang, Xiaochen; Su, Shulan; Cui, Wenxia; Liu, Pei; Duan, Jin-ao; Guo, Jianming; Li, Zhenhao; Shang, Erxin; Qian, Dawei; Huang, Zhijun

    2014-07-01

    In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results.

  12. A UPLC-MS/MS approach for simultaneous determination of eight flavonoids in rat plasma, and its application to pharmacokinetic studies of Fu-Zhu-Jiang-Tang tablet in rats.

    PubMed

    Tao, Yi; Chen, Xi; Jiang, Yanhui; Cai, Baochang

    2017-03-01

    The purpose of this study is to establish and validate a UPLC-MS/MS approach to determine eight flavonoids in biological samples and apply the method to pharmacokinetic study of Fu-Zhu-Jiang-Tang tablet. A Waters BEH C18 UPLC column was employed with methanol/0.1% formic acid-water as mobile phases. The mass analysis was carried out in a triple quadrupole mass spectrometer using multiple reaction monitoring with negative scan mode. A one-step protein precipitation by methanol was used to extract the analytes from blood. Eight major flavonoids were selected as markers. Our results showed that calibration curves for 3'-hydroxypuerarin, mirificin, puerarin, 3'-methoxypuerarin, daidzin, rutin, astragalin and daidzein displayed good linear regression (r(2)  > 0.9986). The intra-day and inter-day precisions (RSD) of the eight flavonoids at high, medium and low levels were <8.03% and the bias of the accuracies ranged from -5.20 to 6.75%.The extraction recoveries of the eight flavonoids were from 91.4 to 100.5% and the matrix effects ranged from 89.8 to 103.8%. The validated approach was successfully applied to a pharmacokinetic study in Sprague-Dawley rats after oral administration of FZJT tablet. Double peaks were emerged in curves of mean plasma concentration for 3'-methoxypuerarin, which was reported for the first time.

  13. 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

  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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Experimental and molecular docking investigation on metal-organic framework MIL-101(Cr) as a sorbent for vortex assisted dispersive micro-solid-phase extraction of trace 5-nitroimidazole residues in environmental water samples prior to UPLC-MS/MS analysis.

    PubMed

    Lu, Nan; Wang, Ting; Zhao, Pan; Zhang, Lianjun; Lun, Xiaowen; Zhang, Xueli; Hou, Xiaohong

    2016-11-01

    In the presented work, metal-organic framework (MOF) material MIL-101(Cr) (MIL, Matérial Institute Lavoisier) was used as a sorbent for vortex assisted dispersive micro-solid-phase extraction (VA-D-μ-SPE) of trace amount of metronidazole (MNZ), ronidazole (RNZ), secnidazole (SNZ), dimetridazole (DMZ), tinidazole (TNZ), and ornidazole (ONZ) in different environmental water samples. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was used to quantify the target analytes. The extraction conditions, including type of sorbents, amount of MIL-101(Cr), solution pH, extraction method, extraction time, effect of salt, and elution conditions were investigated. Upon the optimal conditions, the developed method showed an excellent extraction performance with the average recovery ranging from 75.2 to 98.8 %. Good sensitivity levels were achieved with the detection limits of 0.03∼0.06 μg/L and the quantitation limits of 0.09∼0.20 μg/L. The linear ranges were varied from 0.1 to 20 for SNZ and ONZ and from 0.2 to 40 μg/L for MNZ, RNZ, DMZ, and TNZ (r (2) > 0.992), and repeatability of the method was satisfactory with the relative standard deviations (RSD) <8 %. Ultimately, the applicability of the method was successfully confirmed by the extraction and determination of 5-nitroimidazoles (5-NDZs) in 12 real water samples, showing the positive findings of MNZ and TNZ ranging from 0.3 to 1.0 μg/L. Furthermore, molecular docking was applied to explain the molecular interactions and free binding energies between MIL-101(Cr) and 5-NDZs, providing a deep insight into the adsorption mechanism. The proposed method exhibited the advantages of simplicity, rapidly, less solvent consumption, ease of operation, higher sensitivity, and lower matrix effect. Graphical abstract Schematic diagram of the extraction process and molecular docking investigation.

  20. Simultaneous quantification of four indole alkaloids in Catharanthus roseus cell line C20hi by UPLC-MS.

    PubMed

    He, Lihong; Yang, Li; Xiong, Aizhen; Zhao, Shujuan; Wang, Zhengtao; Hu, Zhibi

    2011-01-01

    An ultra-performance liquid chromatography/mass spectrometry method to simultaneously quantify vindoline, catharanthine, serpentine and ajmalicine in Catharanthus roseus cell line C20hi is reported. Samples were extracted with 1% acetic acid, basified to pH 10 with ammonia, then extracted with ethyl acetate, dried, reconstituted with methanol-1% acetic acid water solution (1:1, v/v) and analyzed using an acetonitrile-0.1% formic acid gradient as the mobile phase. Detection was carried out by electrospray ionization mass spectrometry in the positive-ion mode with selective ion monitoring. The analysis of one sample was achieved in 6 min. The limits of detection were 0.46 - 0.70 ng/ml in cell samples, and 0.10 - 0.16 ng/ml in medium samples. The linearity of detection was over the wide range of 1.00 - 6250.0 ng/ml. Intra- and inter-day accuracies (recovery 88.0 - 111.8%) and precision (RSD 1.25 - 7.81%) showed the performance of the assay. This method provides a more sensitive and high-throughput technique to quantify the four alkaloids in large amount of samples, and will be helpful in high-production cultivar screening.

  1. Determination of Serotonin and Dopamine Metabolites in Human Brain Microdialysis and Cerebrospinal Fluid Samples by UPLC-MS/MS: Discovery of Intact Glucuronide and Sulfate Conjugates

    PubMed Central

    Suominen, Tina; Uutela, Päivi; Ketola, Raimo A.; Bergquist, Jonas; Hillered, Lars; Finel, Moshe; Zhang, Hongbo; Laakso, Aki; Kostiainen, Risto

    2013-01-01

    An UPLC-MS/MS method was developed for the determination of serotonin (5-HT), dopamine (DA), their phase I metabolites 5-HIAA, DOPAC and HVA, and their sulfate and glucuronide conjugates in human brain microdialysis samples obtained from two patients with acute brain injuries, ventricular cerebrospinal fluid (CSF) samples obtained from four patients with obstructive hydrocephalus, and a lumbar CSF sample pooled mainly from patients undergoing spinal anesthesia in preparation for orthopedic surgery. The method was validated by determining the limits of detection and quantification, linearity, repeatability and specificity. The direct method enabled the analysis of the intact phase II metabolites of 5-HT and DA, without hydrolysis of the conjugates. The method also enabled the analysis of the regioisomers of the conjugates, and several intact glucuronide and sulfate conjugates were identified and quantified for the first time in the human brain microdialysis and CSF samples. We were able to show the presence of 5-HIAA sulfate, and that dopamine-3-O-sulfate predominates over dopamine-4-O-sulfate in the human brain. The quantitative results suggest that sulfonation is a more important phase II metabolism pathway than glucuronidation in the human brain. PMID:23826355

  2. Chiral PCB 91 and 149 Toxicity Testing in Embryo and Larvae (Danio rerio): Application of Targeted Metabolomics via UPLC-MS/MS

    PubMed Central

    Chai, Tingting; Cui, Feng; Yin, Zhiqiang; Yang, Yang; Qiu, Jing; Wang, Chengju

    2016-01-01

    In this study, we aimed to investigate the dysfunction of zebrafish embryos and larvae induced by rac-/(+)-/(−)- PCB91 and rac-/(−)-/(+)- PCB149. UPLC-MS/MS (Ultra-performance liquid chromatography coupled with mass spectrometry) was employed to perform targeted metabolomics analysis, including the quantification of 22 amino acids and the semi-quantitation of 22 other metabolites. Stereoselective changes in target metabolites were observed in embryos and larvae after exposure to chiral PCB91 and PCB149, respectively. In addition, statistical analyses, including PCA and PLS-DA, combined with targeted metabolomics were conducted to identify the characteristic metabolites and the affected pathways. Most of the unique metabolites in embryos and larvae after PCB91/149 exposure were amino acids, and the affected pathways for zebrafish in the developmental stage were metabolic pathways. The stereoselective effects of PCB91/149 on the metabolic pathways of zebrafish embryos and larvae suggest that chiral PCB91/149 exposure has stereoselective toxicity on the developmental stages of zebrafish. PMID:27629264

  3. Chiral PCB 91 and 149 Toxicity Testing in Embryo and Larvae (Danio rerio): Application of Targeted Metabolomics via UPLC-MS/MS

    NASA Astrophysics Data System (ADS)

    Chai, Tingting; Cui, Feng; Yin, Zhiqiang; Yang, Yang; Qiu, Jing; Wang, Chengju

    2016-09-01

    In this study, we aimed to investigate the dysfunction of zebrafish embryos and larvae induced by rac-/(+)-/(‑)- PCB91 and rac-/(‑)-/(+)- PCB149. UPLC-MS/MS (Ultra-performance liquid chromatography coupled with mass spectrometry) was employed to perform targeted metabolomics analysis, including the quantification of 22 amino acids and the semi-quantitation of 22 other metabolites. Stereoselective changes in target metabolites were observed in embryos and larvae after exposure to chiral PCB91 and PCB149, respectively. In addition, statistical analyses, including PCA and PLS-DA, combined with targeted metabolomics were conducted to identify the characteristic metabolites and the affected pathways. Most of the unique metabolites in embryos and larvae after PCB91/149 exposure were amino acids, and the affected pathways for zebrafish in the developmental stage were metabolic pathways. The stereoselective effects of PCB91/149 on the metabolic pathways of zebrafish embryos and larvae suggest that chiral PCB91/149 exposure has stereoselective toxicity on the developmental stages of zebrafish.

  4. 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.

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

    PubMed

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

    2015-07-01

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

  6. 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...

  7. 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...

  8. A UPLC/MS/MS method for determination of protosappanin B in rat plasma and its application of a pharmacokinetic and bioavailability study.

    PubMed

    Chen, Wei-Ying; Zhou, Xian-Zhen; Wu, Li-Lan; Wu, Yun-Shan; Wang, Shu-Mei; Liu, Bo; Guo, De-An

    2016-12-14

    Caesalpinia sappan L. is a traditional medicinal plant which is used for promoting blood circulation and cerebral apoplexy therapy in China. Previous reports showed that the extracts of Caesalpinia sappan L. could exert vasorelaxant activity and anti-inflammation activity. Protosappanin B is a major constituent of C. sappan L., and showed several important bioactivities. The separation was achieved by an Acquity UPLC BEH Symmetry Shield RP18 column (1.7 μm, 2.1 × 100 mm) column with the gradient mobile phase consisting of 5 mm ammonium acetate aqueous solution and acetonitrile. Detection was carried out by using negative-ion electrospray tandem mass spectrometry via multiple reaction monitoring. Plasma samples were preprocessed by an extraction with ethyl acetate, and apigenin was used as internal standard. The current UPLC-MS/MS assay was validated for linearity, accuracy, intraday and interday precisions, stability, matrix effects and extraction recovery. After oral and intravenous administration, the main pharmacokinetic parameters were as follows: peak concentrations, 83.5 ± 46.2 and 1329.6 ± 343.6 ng/mL; areas under the concentration-time curve, 161.9 ± 69.7 and 264.9 ± 56.3 μg h/L; and half-lives, 3.4 ± 0.9 and 0.3 ± 0.1 h, respectively. The absolute bioavailability in rats of protosappanin B was 12.2%. The method has been successfully applied to a pharmacokinetic and bioavailability study of protosappanin B in rats.

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

    PubMed

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

    2013-12-15

    Freeze-dried fenugreek (Trigonella foenum-graecum) seeds and bitter melon (Momordica charantia) fruit were extracted sequentially using non-polar to polar solvents, with further separation carried out on polar extracts by molecular weight cut off dialysis. The fenugreek ethyl acetate crude extract (FGE3) demonstrated the highest antioxidant activity, in terms of Trolox Equivalents (TE), for both the DPPH (35.338±0.908 mg TE/g) and FRAP (77.352±0.627 mg TE/g) assays. This extract also contained the highest phenolic content, in terms of Gallic Acid Equivalents (GAE) (106.316±0.377 mg GAE/g). Despite having considerably lower antioxidant activity than fenugreek, the highest antioxidant activities for bitter fruit were observed in the hexane (BME1) and methanol hydrophilic<3.5 kDa dialysed (BME4<3.5 kDa) extracts, while the highest phenolic content was found in the methanol hydrophilic>3.5 kDa (BME4>3.5 kDa) dialysed extract. UPLC-MS was used to quantify 18 phenolic compounds from fenugreek and 13 from bitter melon in active crude extracts. The flavonoids apigenin-7-O-glycoside (1955.55 ng/mg) and luteolin-7-O-glycoside (725.50 ng/mg) were the most abundant compounds in FGE3, while bitter melon extracts contained only small amounts of mainly phenolic acids. A further 5 fenugreek and 1 bitter melon compounds were identified in trace amounts from the same extracts, respectively.

  10. Differentiation of Schisandra chinensis and Schisandra sphenanthera using metabolite profiles based on UPLC-MS and GC-MS.

    PubMed

    Guo, Zhiyong; Zhao, Aihua; Chen, Tianlu; Xie, Guoxiang; Zhou, Mingmei; Qiu, Mingfeng; Jia, Wei

    2012-01-01

    Historically, Schisandra chinensis and S. sphenanthera have been widely used in traditional Chinese medicine. Although both species are in the genus Schisandra, they have dissimilar therapeutic effects that may be attributed to compositional differences in secondary metabolites. We developed a method to compare these metabolites obtained from the above plant species using ultra-performance liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry coupled with multivariate statistical analyses. The critical markers we used to discriminate between both plant species resulted in the identification and quantification of six lignans and seven essential oils. We believe that our approach provided a sensitive, reliable and robust method to conveniently classify medicinal plants that can be used to explore subtle variations among different species or plants from different geographical locations.

  11. Development and validation of UPLC-MS/MS method for simultaneous determination of gestodene and ethinyl estradiol in rat plasma.

    PubMed

    Xiong, Zhili; Sun, Xiaohong; Huo, Taoguang; Li, Ning; Zheng, Yan; Sun, Yi

    2010-02-01

    A selective and sensitive ultra-performance liquid chromatography method with tandem mass spectrometric detection for simultaneous determination of gestodene (GES) and ethinyl estradiol (EE) in rat plasma was developed and validated. GES, EE and the internal standard, norgestrel, were extracted with ethyl acetate, derivatized (EE only) with dansyl chloride and then back-extracted into diethyl ether-hexane (2:1, v/v). The separation was performed on an ACQUITY UPLC BEH C(18) column with gradient elution using mobile phase consisting of acetonitrile and water (both containing 0.1% formic acid). The detection was carried out by means of electrospray ionization (ESI) mass spectrometry in positive ion mode with multiple-reaction monitoring. Calibration curves of GES and EE were linear (r(2) >or= 0.99) over the concentration ranges 1.59-159 and 0.196-78.4 ng/mL, respectively. The intra- and inter-day precisions were not more than 6.9 and 12.9% for GES and 10.6 and 9.0% for EE, and the accuracies were -2.5-8.0% for GES, and -7.2-0.19% for EE, respectively. The method herein described was superior to previous methods and was applicable to the pharmacokinetic study of GES and EE in rats.

  12. Clenbuterol determination in calf hair by UPLC-MS-MS: case report of a fraudulent use for cattle growth.

    PubMed

    Salquèbre, Guillaume; Bresson, Marie; Villain, Marion; Cirimele, Vincent; Kintz, Pascal

    2007-03-01

    A method for clenbuterol determination in hair has been developed. Hair specimens collected from two calves were decontaminated using hot water followed by methylene chloride. Hair was cut into small pieces, and 100 mg was incubated in 1 mL 0.1M hydrochloric acid overnight at 45 degrees C in the presence of 1 ng acebutolol used as internal standard. After neutralization with 1 mL 0.1M NaOH, 2 mL of bicarbonate buffer (pH 8.6) were added and the preparation was then purified using solid-phase extraction with an Isolute C18 column. Methanolic eluent was evaporated to dryness and the residue was reconstituted with 50 microL methanol. A 5-microL portion was injected onto an ACQUITY UPLC BEH C18 column (2.1 x 50 mm, 1.7 microm) and separation was achieved using a gradient of acetonitrile and formate buffer delivered at a flow rate of 0.6 mL/min. Detection was done on a Waters Micromass Quattro Micro API triple-quadrupole mass spectrometer. Ionization was achieved using electrospray in positive mode. Clenbuterol was identified by two transitions (m/z 277.1 > 203.2 and m/z 277.1 > 132.1). Quantitation was performed with the most intensive transition (m/z 277.1 > 203.2) versus the internal standard monitored using the transition (m/z 337.3 > 116.1). When compared with gas chromatography methods that are generally used for the determination of beta-adrenergics, the major advantages of this method were the sensitivity, a shorter run time, and the absence of a derivatization step. The analysis of two hair samples from calves suspected of drug administration showed low clenbuterol concentrations at 3.6 and 4.8 pg/mg.

  13. 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.

  14. 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...

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

    PubMed

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

    2013-04-01

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

  16. 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

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

    PubMed

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

    2015-01-01

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

  18. Fractional factorial design-based optimisation and application of an extraction and UPLC-MS/MS detection method for the quantification of phytosterols in food, feed and beverages low in phytosterols.

    PubMed

    Decloedt, Anneleen I; Van Landschoot, Anita; Vanhaecke, Lynn

    2016-11-01

    Phytosterols are ubiquitous in plants, as they play an important role in cell membrane stability and as signal transducers. Over the last few decades, scientific interest in phytosterols has significantly increased. Most of the interest has focused on the cholesterol-lowering properties of phytosterols, but they may also interfere with endogenous steroid hormone synthesis. Despite this dual interest in phytosterols, accurate and fully validated methods for the quantification of phytosterols in food and feed samples are scarce. During this study an extraction and detection method for the main free phytosterols (β-sitosterol, campesterol, stigmasterol and brassicasterol) was optimised using a fractional factorial design. Detection was carried out on a UPLC-MS/MS triple stage quadrupole apparatus. The extraction and UPLC-MS/MS detection method was fully validated according to EU Council Decision 2002/657 guidelines and Association of Analytical Chemists (AOAC) MS criteria, reaching all evaluated performance parameter requirements. The individual recoveries ranged between 95 and 104 %. Good results for repeatability and intralaboratory reproducibility (RSD %) were observed (<10 %). Excellent linearity was proven on the basis of determination coefficient (R (2) > 0.99) and lack-of-fit test (F test, alpha = 0.05). The limits of detection (LODs) and lower limits of quantification (LLOQs) in grain matrices were as low as 0.01-0.03 mg per 100 g and 0.02-0.10 mg per 100 g. This method allowed quantification of all main, free phytosterols in different grains (oats, barley, corn, malt) and it was shown that the method can be used for other solid food and feed samples as well, including new matrices such as straw, hay, mustard seeds, grass and yellow peas. Additionally, the method was shown to perform well in liquid samples low in phytosterols such as concentrate-based juices, soft drinks and beers (<5 μg per 100 mL). Graphical Abstract An extraction and

  19. Subzero-Temperature Liquid-Liquid Extraction Coupled with UPLC-MS-MS for the Simultaneous Determination of 12 Bioactive Components in Traditional Chinese Medicine Gegen-Qinlian Decoction.

    PubMed

    Shi, Zhihong; Li, Zhimin; Zhang, Shulan; Fu, Hongna; Zhang, Hongyi

    2015-09-01

    Based on the phase separation phenomenon of acetonitrile-water system at subzero temperature, a subzero-temperature liquid-liquid extraction coupled with ultra-performance liquid chromatography tandem quadrupole mass spectrometry : UPLC-MS-MS) method was developed for the simultaneous determination of 12 bioactive components in Gegen-Qinlian decoction. After optimization, the extraction conditions were set as follows: 3.0 mL of aqueous sample solution (pH 5.86) was extracted with 2 mL of acetonitrile at -35°C for 35 min. The separated acetonitrile phase was diluted 10-fold with water before UPLC-MS-MS analysis. Separation was performed on a Waters ACQUITY UPLC(®)BEH C18 column (2.1 × 100 mm i.d., 1.7 µm) with ammonium formate buffer solution (20 mmol L(-1), pH 3.2, adjusted by formic acid) and acetonitrile as mobile phase with gradient elution. Twelve target components could be separated within 10 min and quantified in multiple reaction monitoring mode, both positive and negative ionization modes were employed. Limits of detection were in the range of 0.0003-0.0451 μg mL(-1). Relative standard deviation values for intra- and interday precision were <2.71 and 8.94%, respectively. The established method provides a simple and effective framework for the quality control of Gegen-Qinlian decoction and related traditional Chinese medicinal preparations.

  20. 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.…

  1. 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

  2. [Determination of di (hydrogenated tallow alkyl) dimethyl ammonium compounds in textile auxiliaries by ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhu, Feng

    2015-01-01

    A method has been developed for the determination of di (hydrogenated tallow alkyl) dimethyl ammonium compounds (DHTDMAC) in textile auxiliaries by ultra-high performance liquid chromatography-tandem mass spectrometry. (UPLC-MS/MS). The samples were extracted and diluted with acidified methanol by 5% (v/v) formic acid under ultrasonic assistance. The separation was performed on an Eclipse Plus C18 column (50 mm x 2.1 mm, 1.8 microm) using 0.1% (v/v) formic acid solution and methanol as the mobile phases. Identification and quantification were achieved by UPLC-MS/MS with electrospray ionization (ESI) source in positive ion mode and multiple reaction monitoring (MRM) mode. The results indicated that the calibration curve of DHTDMAC showed good linear relationship between peak area and mass concentration in the range of 10-280 microg/L with the correlation coefficient (r2) of 0.9991. The limit of detection (LOD, S/N=3) and the limit of quantification (LOQ, S/N= 10) of this method were 3 mg/kg and 10 mg/kg, respectively. The average recoveries from three typical textile auxiliary matrices including dispersant, antistatic agent and fabric softener, at three spiked levels were in the range of 97.2%-108.3% with the relative standard deviations (RSDs) of 1.5%-4.6%. The method is sensitive, accurate, simple and effective for the analysis of DHTDMAC in textile auxiliaries.

  3. [Rapid simultaneous screening and detection of ten anticoagulant rodenticides in foods by ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhu, Feng; Liu, Hualiang; Chen, Bei; Rong, Weiguang; Ma, Yongjian

    2013-05-01

    A rapid method for the simultaneous screening and detection of ten anticoagulant rodenticides in foods was developed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After the extraction by acetonitrile and clean-up by QuEChERS, the extract was separated on a Poroshell 120 EC-C18 column (100 mm x 2.1 mm, 2.7 microm) with the gradient elution of 5 mmol/L ammonium acetate and acetonitrile. The detection was carried out by UPLC-MS/MS using a negative electrospray ionization interface in multiple reaction monitoring (MRM) mode. The ten anticoagulant rodenticides showed a good linear relationship (r > 0.99) in the range of 5 - 500 microg/L. In the four samples of chili sauce, flour, vinegar and soy sauce, the spiked recoveries were in the range of 72.6% - 112%, and the relative standard deviations (RSD) were all not more than 11.2%. The limits of detection (LOD) were all in the range of 0.5 - 4.5 microg/kg. This method is rapid, simple, sensitive, accurate and of good specificity for the satisfactory rapid screening and detection of the ten anticoagulant rodenticides in the sudden public health security events.

  4. A high-throughput multicomponent screening method for diuretics, masking agents, central nervous system (CNS) stimulants and opiates in human urine by UPLC-MS/MS.

    PubMed

    Thörngren, John-Olof; Ostervall, Fredrik; Garle, Mats

    2008-07-01

    A simple and rapid multicomponent screening method of 130 substances for direct injections of urine samples has been developed. The fully automated method based on ultra-performance liquid chromatography (UPLC) and tandem mass spectrometry (MS/MS) is used for three different classes of doping agents: diuretics, central nervous system stimulants (CNS stimulants) and opiates. The samples are diluted with buffer containing internal standards (IS) by a pipetting robot system into 96-well plates. Samples are injected on a reversed phase sub 2-microm particle column connected to a fast polarity switching and rapid scanning tandem mass spectrometer with an electrospray interface. The software used to evaluate the results produced reports containing a small-sized window for each component and a data table list with flags to indicate any adverse analytical findings in the sample. The report can also be processed automatically using an application software, which interpret the data and indicate if there is a suspicious sample. One 96-well plate can be analyzed within 16 h.

  5. 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

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

    PubMed

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

    2015-09-11

    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 (13)C-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.

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

    PubMed

    Wang, Xiupin; Li, Peiwu

    2015-04-15

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Stevens, Jack; Dowell, Dawn

    2012-01-01

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

  10. A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of D-amino acids in body fluids.

    PubMed

    Visser, Wouter F; Verhoeven-Duif, Nanda M; Ophoff, Roel; Bakker, Steven; Klomp, Leo W; Berger, Ruud; de Koning, Tom J

    2011-10-07

    D-Amino acids are increasingly being recognized as important signaling molecules in mammals, including humans. D-Serine and D-aspartate are believed to act as signaling molecules in the central nervous system. Interestingly, several other D-amino acids also occur in human plasma, but very little is currently known regarding their function and origin. Abnormal levels of D-amino acids have been implicated in the pathogenesis of different diseases, including schizophrenia and amyotrophic lateral sclerosis (ALS), indicating that D-amino acid levels hold potential as diagnostic markers. Research into the biological functions of D-amino acids is hindered, however, by the lack of sufficiently sensitive, high-throughput analytical methods. In particular, the interference of large amounts of L-amino acids in biological samples and the low concentrations of D-amino acids are challenging. In this paper, we compared 7 different chiral derivatization agents for the analysis of D-amino acids and show that the chiral reagent (S)-NIFE offers outstanding performance in terms of sensitivity and enantioselectivity. An UPLC-MS/MS based method for the quantification of D-amino acids human biological fluids was then developed using (S)-NIFE. Baseline separation (R(s)>2.45) was achieved for the isomers of all 19 chiral proteinogenic amino acids. The limit of detection was <1 nM for all amino acids except d-alanine (1.98 nM), d-methionine (1.18 nM) and d-asparagine (5.15 nM). For measurements in human plasma, cerebrospinal fluid and urine, the accuracy ranged between 85% and 107%. The intra-assay and inter-assay were both <16% RSD for these three different matrices. Importantly, the method does not suffer from spontaneous racemization during sample preparation and derivatization. Using the described method, D-amino acid levels in human cerebrospinal fluid, plasma and urine were measured.

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

    PubMed

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

    2016-02-15

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

  12. UPLC-MS/MS assay for the simultaneous quantification of carvedilol and its active metabolite 4'-hydroxyphenyl carvedilol in human plasma to support a bioequivalence study in healthy volunteers.

    PubMed

    Patel, Daxesh P; Sharma, Primal; Sanyal, Mallika; Singhal, Puran; Shrivastav, Pranav S

    2013-08-01

    An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of carvedilol and its pharmacologically active metabolite 4'-hydroxyphenyl carvedilol in human plasma using their deuterated internal standards (IS). Samples were prepared by solid-phase extraction using 100 μL human plasma. Chromatographic separation of analytes was achieved on UPLC C18 (50 × 2.1 mm, 1.7 µm) column using acetonitrile-4.0 mM ammonium formate, pH 3.0 adjusted with 0.1% formic acid (78:22, v/v) as the mobile phase. The multiple reaction monitoring transitions for both the analytes and IS were monitored in the positive electrospray ionization mode. The method was validated over a concentration range of 0.05-50 ng/mL for carvedilol and 0.01-10 ng/mL for 4'-hydroxyphenyl carvedilol. Intra- and inter-batch precision (% CV) and accuracy for the analytes varied from 0.74 to 3.88 and 96.4 to 103.3% respectively. Matrix effect was assessed by post-column analyte infusion and by calculation of precision values (coefficient of variation) in the measurement of the slope of calibration curves from eight plasma batches. The assay recovery was within 94-99% for both the analytes and IS. The method was successfully applied to support a bioequivalence study of 12.5 mg carvedilol tablets in 34 healthy subjects.

  13. Metabonomic analysis of urine from rats after low-dose exposure to 3-chloro-1,2-propanediol using UPLC-MS.

    PubMed

    Liu, Liyan; He, Yujie; Lu, Huimin; Wang, Maoqing; Sun, Changhao; Na, Lixin; Li, Ying

    2013-05-15

    To study the toxic effect of chronic exposure to 3-chloro-1,2-propanediol (3-MCPD) at low doses, a metabonomics approach based on ultrahigh-performance liquid chromatography and quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was performed. Two different doses of 3-MCPD (1.1 and 5.5mg/kg bw/d) were administered to Wistar rats for 120 days (1.1mg/kg bw/d: lowest observed adverse effect level [LOAEL]). The metabolite profiles and biochemical parameters were obtained at five time points after treatment. For the 3-MCPD-treated groups, a significant change in urinary N-acetyl-β-d-glucosaminidase and β-d-galactosidase was detected on day 90, while some biomarkers based on the metabonomics, such as N-acetylneuraminic acid, N-acetyl-l-tyrosine, and gulonic acid, were detected on day 30. These results suggest that these biomarkers changed more sensitively and earlier than conventional biochemical parameters and were thus considered early and sensitive biomarkers of exposure to 3-MCPD; these biomarkers provide more information on toxicity than conventional biochemical parameters. These results might be helpful to investigate the toxic mechanisms of 3-MCPD and provide a scientific basis for assessing the effect of chronic exposure to low-dose 3-MCPD on human health.

  14. Highly sensitive plasmonic silver nanorods.

    PubMed

    Jakab, Arpad; Rosman, Christina; Khalavka, Yuriy; Becker, Jan; Trügler, Andreas; Hohenester, Ulrich; Sönnichsen, Carsten

    2011-09-27

    We compare the single-particle plasmonic sensitivity of silver and gold nanorods with similar resonance wavelengths by monitoring the plasmon resonance shift upon changing the environment from water to 12.5% sucrose solution. We find that silver nanoparticles have 1.2 to 2 times higher sensitivity than gold, in good agreement with simulations based on the boundary-elements-method (BEM). To exclude the effect of particle volume on sensitivity, we test gold rods with increasing particle width at a given resonance wavelength. Using the Drude-model of optical properties of metals together with the quasi-static approximation (QSA) for localized surface plasmons, we show that the dominant contribution to higher sensitivity of silver is the lower background polarizability of the d-band electrons and provide a simple formula for the sensitivity. We improve the reversibility of the silver nanorod sensors upon repeated cycles of environmental changes by blocking the high energy parts of the illumination light.

  15. HILIC-UPLC-MS/MS combined with hierarchical clustering analysis to rapidly analyze and evaluate nucleobases and nucleosides in Ginkgo biloba leaves.

    PubMed

    Yao, Xin; Zhou, Guisheng; Tang, Yuping; Guo, Sheng; Qian, Dawei; Duan, Jin-Ao

    2015-02-01

    Ginkgo biloba leaf extract has been widely used in dietary supplements and more recently in some foods and beverages. In addition to the well-known flavonol glycosides and terpene lactones, G. biloba leaves are also rich in nucleobases and nucleosides. To determine the content of nucleobases and nucleosides in G. biloba leaves at trace levels, a reliable method has been established by using hydrophilic interaction ultra performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC-UPLC-TQ-MS/MS) working in multiple reaction monitoring mode. Eleven nucleobases and nucleosides were simultaneously determined in seven min. The proposed method was fully validated in terms of linearity, sensitivity, and repeatability, as well as recovery. Furthermore, hierarchical clustering analysis (HCA) was performed to evaluate and classify the samples according to the contents of the eleven chemical constituents. The established approach could be helpful for evaluation of the potential values as dietary supplements and the quality control of G. biloba leaves, which might also be utilized for the investigation of other medicinal herbs containing nucleobases and nucleosides.

  16. 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.

  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.

  18. 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.

  19. 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.

  20. 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.…

  1. High-sensitivity magnetic profiling

    SciTech Connect

    Unterberger, R.R.

    1983-05-01

    A high sensitivity rubidium 87 magnetometer, designed and built by the author, is used at sea to make magnetic profiles over subsurface structures of interest. The Texas AandM University Research Vessel GYRE was used to launch, tow and recover a nonmagnetic fiberglass skiff that carried the magnetometer. To avoid magnetic field disturbances of the GYRE, the skiff with the magnetometer was towed 600 ft behind the ship. Loran C, and sometimes SATNAV, position data were used to determine the ship location. Two recording depth finders using 3.5 kHz and 12 kHz respectively were used to profile the bottom. Time marks were plotted on the magnetic and sonar data in accordance with WWV time signals received on 10 MHz. (15 MHz and 5 MHz were also available if there happened to be poor radio transmission at 10 MHz). Magnetic data were recorded in digital form on a strip chart recorder, using the last two digits of the six digit resonance frequency of the Rb 87 atoms.

  2. High-throughput and sensitive screening by ultra-performance liquid chromatography tandem mass spectrometry of diuretics and other doping agents.

    PubMed

    Ventura, Rosa; Roig, M; Montfort, N; Sáez, P; Bergés, Rosa; Segura, Jordi

    2008-01-01

    The reliability of ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC- MS/MS) for high throughput screening in anti-doping control has been tested. A method to screen for the presence of diuretics and other doping agents in urine has been optimised and validated. The extraction procedure consisted of an alkaline extraction (pH 9.5) with ethyl acetate and salting-out effect (sodium chloride). The extracts were analysed by UPLC-MS/MS. Analysis of 34 forbidden drugs and metabolites was achieved in a total run time of 5 min, using a C18 column (100 mm x 2.1 mm i.d., 1.7 microm particle size) and a mobile phase containing deionised water and acetonitrile with formic acid, with gradient elution at a flow-rate of 0.6 mL min(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionisation in positive- or negative-ion mode. Precursor and product ions were studied for each compound and cone voltage and collision energy were optimised. Due to the different chemical structure of the compounds under study, extraction recoveries varied from less than 10% to 100% depending on the analyte. The limits of detection ranged from 50 ng mL(-1) to 200 ng mL(-1), and all the compounds comply with the requirements of quality established by the World Anti-doping Agency. Intra-assay precision was evaluated at two concentrations for each compound and, in most cases, a relative standard deviation of the signal ratio lower than 20% was obtained. The method has demonstrated to be reliable when analysing routine samples and the short analysis time resulting from a simple sample preparation and a rapid instrumental analysis allow a fast turn-around time and makes it of great interest for routine anti-doping control purposes.

  3. High sensitivity RNA pseudoknot prediction.

    PubMed

    Huang, Xiaolu; Ali, Hesham

    2007-01-01

    Most ab initio pseudoknot predicting methods provide very few folding scenarios for a given RNA sequence and have low sensitivities. RNA researchers, in many cases, would rather sacrifice the specificity for a much higher sensitivity for pseudoknot detection. In this study, we introduce the Pseudoknot Local Motif Model and Dynamic Partner Sequence Stacking (PLMM_DPSS) algorithm which predicts all PLM model pseudoknots within an RNA sequence in a neighboring-region-interference-free fashion. The PLM model is derived from the existing Pseudobase entries. The innovative DPSS approach calculates the optimally lowest stacking energy between two partner sequences. Combined with the Mfold, PLMM_DPSS can also be used in predicting complicated pseudoknots. The test results of PLMM_DPSS, PKNOTS, iterated loop matching, pknotsRG and HotKnots with Pseudobase sequences have shown that PLMM_DPSS is the most sensitive among the five methods. PLMM_DPSS also provides manageable pseudoknot folding scenarios for further structure determination.

  4. High sensitivity radon emanation measurements.

    PubMed

    Zuzel, G; Simgen, H

    2009-05-01

    The presented radon detection technique employs miniaturized ultra-low background proportional counters. (222)Rn samples are purified, mixed with a counting gas and filled into a counter using a special glass vacuum line. The absolute sensitivity of the system is estimated to be 40 microBq (20 (222)Rn atoms). For emanation investigations two metal sealed stainless steel vessels and several glass vials are available. Taking into account their blank contributions, measurements at a minimum detectable activity of about 100 microBq can be performed.

  5. 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.

  6. 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.

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

    SciTech Connect

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

    2016-02-07

    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.

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

    PubMed

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

    2016-01-01

    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.

  9. High sensitivity knitted fabric strain sensors

    NASA Astrophysics Data System (ADS)

    Xie, Juan; Long, Hairu; Miao, Menghe

    2016-10-01

    Wearable sensors are increasingly used in smart garments for detecting and transferring vital signals and body posture, movement and respiration. Existing fabric strain sensors made from metallized yarns have low sensitivity, poor comfort and low durability to washing. Here we report a knitted fabric strain sensor made from a cotton/stainless steel (SS) fibre blended yarn which shows much higher sensitivity than sensors knitted from metallized yarns. The fabric feels softer than pure cotton textiles owing to the ultrafine stainless steel fibres and does not lose its electrical property after washing. The reason for the high sensitivity of the cotton/SS knitted fabric sensor was explored by comparing its sensing mechanism with the knitted fabric sensor made from metallized yarns. The results show that the cotton/SS yarn-to-yarn contact resistance is highly sensitive to strain applied to hooked yarn loops.

  10. High Sensitivity deflection detection of nanowires

    SciTech Connect

    Sanii, Babak; Ashby, Paul

    2009-10-28

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

  11. High sensitivity optically pumped quantum magnetometer.

    PubMed

    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/Hz(½) over a bandwidth of 26 Hz and that this sensitivity drops to 130 pT/Hz(½) 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.

  12. A UPLC-MS/MS Method for Simultaneous Determination of Free and Total Forms of a Phenolic Acid and Two Flavonoids in Rat Plasma and Its Application to Comparative Pharmacokinetic Studies of Polygonum capitatum Extract in Rats.

    PubMed

    Huang, Yong; Sun, Hui-Yuan; Qin, Xiao-Li; Li, Yong-Jun; Liao, Shang-Gao; Gong, Zi-Peng; Lu, Yuan; Wang, Yong-Lin; Wang, Ai-Min; Lan, Yan-Yu; Zheng, Lin

    2017-02-25

    The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum capitatum in vivo and to conduct pharmacokinetic studies on the herb, a well-known Miao medicinal plant in China. Gallic acid, quercitrin, and quercetin were analysed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Protein precipitation in plasma samples was performed using methanol. For the determination of total forms of analytes, an additional process of hydrolysis was conducted using β-glucuronidase and sulphatase. The analytes were separated on a BEH C18 column (50 mm × 2.1 mm; i.d., 1.7 μm) and quantified by multiple reaction monitoring (MRM) mode. The linear regression showed high linearity over a 729-fold dynamic range for the three analytes. The relative standard deviations of intra- and inter-day measurements were less than 9.5%, and the method was accurate to within -11.1% to 12.5%. The extraction recoveries for gallic acid, quercitrin, and quercetin were 94.3%-98.8%, 88.9%-98.8%, and 95.7%-98.5%, respectively. All samples were stable under short- and long-term storage conditions. The validated method was successfully applied to a comparative pharmacokinetic study of gallic acid, quercitrin, and quercetin in their free and total forms in rat plasma. The study revealed significantly higher exposure of the constituents in total forms for gallic acid and quercetin, while quercitrin was detected mainly in its corresponding free form in vivo. The established method was rapid and sensitive for the simultaneous quantification of free and total forms of multiple constituents of Polygonum capitatum extract in plasma.

  13. Electrostatic sensitivity of secondary high explosives

    SciTech Connect

    Campos, C.A.

    1980-06-01

    An Electrostatic Sensitivity Test System designed at Pantex was used to evaluate the secondary high explosives PETN, HMX, RDX, HNS I, HNS II and TATB. The purpose of this study was to establish test conditions for a standard electrostatic sensitivity test and measure baseline data of a few secondary explosives. Although secondary explosives are often considered quite insensitive to an electrostatic discharge, PETN, HMX, and RDX were initiated. Several external elements to the high explosive were found to have an influence on sensitivity. Initiation appeared to be dependent on the nature of the discharge current curve. Those elements recognized as having a significant effect on the results were held constant in this study. These included: distance between discharge plates; sample moisture content; material density; and system resistance, capacitance and inductance. However, no attempt was made in this study to determine the extent to which the high explosive response to electrostatic discharge is affected by these factors since such correlation is not necessary to determine relative sensitivities.

  14. High efficiency porphyrin sensitized mesoscopic solar cells

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  15. 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.

  16. A rapid, accurate and sensitive method with the new stable isotopic tags based on microwave-assisted dispersive liquid-liquid microextraction and its application to the determination of hydroxyl UV filters in environmental water samples.

    PubMed

    Li, Xiu; Chen, Guang; Liu, Jianjun; Liu, Yuxia; Zhao, Xianen; Cao, Ziping; Xia, Lian; Li, Guoliang; Sun, Zhiwei; Zhang, Shijuan; Wang, Hua; You, Jinmao

    2017-05-15

    A rapid, accurate and sensitive method, using the stable isotope labeling (SIL), microwave-assisted dispersive liquid-liquid micro extraction (MADLLME) and the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), was developed and validated for the determination of hydroxyl UV Filters in environmental water samples. A pair of new isotopic tags D0-/D3-1-methylindole-3-acetic acid (D0-/D3-MIAA) is synthesized, with which a simple yet efficient pretreatment MADLLME-SIL is developed. Under the optimized conditions (80℃, 240W, 180s), the sample pretreatment including analyte extraction, pre-concentration and isotope labeling can be finished conveniently in only 9min. D0-/D3-MIAA labeling improves the chromatographic retention by strengthening the hydrophobicity and enhances the MS response for 3-4 orders of magnitude. Excellent linearity is established by the H/D ratios of 1/10-10/1 with the correlation coefficients >0.9990. The quite low detection limits (0.54-1.79ng/L) are achieved, ensuring the trace detection. This method is successfully applied to a series of environmental water samples. The recoveries (93.2%~103.5%) are significantly improved and the analysis time is largely reduced (<15min). The excellent sensitivity, accuracy, recovery, and efficiency demonstrate this MADLLME-SIL-LC-MS/MS method a superior alternative for the analysis of UV filters in water samples.

  17. Developments of highly sensitive DNA sensors

    NASA Astrophysics Data System (ADS)

    Ogata, Naoya

    2011-09-01

    The large enhancements of optical properties of the dye-intercalated DNA lead us to apply the dye-intercalated DNA as various sensors with a high sensitivity to detect environmentally toxic gases such as dioxine, NOx or carbon monoxide. This paper retorts on DNA sensors for the further applications of DNA as materials. Also, bio-medical applications of DNA sensors such as a glucose sensor are reported.

  18. [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.

  19. Low Cost, Low Power, High Sensitivity Magnetometer

    DTIC Science & Technology

    2008-12-01

    Guedes , A.; et al., 2008: Hybrid - LOW COST, LOW POWER, HIGH SENSITIVITY MAGNETOMETER A.S. Edelstein*, James E. Burnette, Greg A. Fischer, M.G...Edelstein, 2004; Burnette, 2008), we suggested a method for mitigating the problem of 1/f noise. We and others ( Guedes , 2008) have been utilizing...6. Guedes , A.; et al., 2008: Hybrid - 3magnetoresistive/microelectromechanical devices for static field modulation and sensor 1/f noise

  20. High sensitivity neutron detector for Z

    SciTech Connect

    Ruggles, L.E.; Porter, J.L. Jr.; Simpson, W.W.; Vargas, M.F.; Zagar, D.M.; Hartke, R.; Buersgens, F.; Symes, D.R.; Ditmire, T.

    2004-10-01

    We have developed, calibrated, and tested a high sensitivity neutron detector that can be operated in the harsh x-ray bremsstrahlung environment that exists in experiments conducted on the 20 MA Z z-pinch facility located at Sandia National Laboratories in Albuquerque, New Mexico. The detector uses a scintillator coupled to a microchannel-plate photomultiplier tube detector and extensive x-ray shielding.

  1. Highly sensitive beam steering with plasmonic antenna.

    PubMed

    Rui, Guanghao; Zhan, Qiwen

    2014-08-05

    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.

  2. Cooled membrane for high sensitivity gas sampling.

    PubMed

    Jiang, Ruifen; Pawliszyn, Janusz

    2014-04-18

    A novel sample preparation method that combines the advantages of high surface area geometry and cold surface effect was proposed to achieve high sensitivity gas sampling. To accomplish this goal, a device that enables the membrane to be cooled down was developed for sampling, and a gas chromatograph-mass spectrometer was used for separation and quantification analysis. Method development included investigation of the effect of membrane temperature, membrane size, gas flow rate and humidity. Results showed that high sensitivity for equilibrium sampling, such as limonene sampling in the current study could be achieved by either cooling down the membrane and/or using a large volume extraction phase. On the other hand, for pre-equilibrium extraction, in which the extracted amount was mainly determined by membrane surface area and diffusion coefficient, high sensitivity could be obtained by using thinner membranes with a larger surface and/or a higher sampling flow rate. In addition, humidity showed no significant influence on extraction efficiency, due to the absorption property of the liquid extraction phase. Next, the limit of detection (LOD) was found, and the reproducibility of the developed cooled membrane gas sampling method was evaluated. Results showed that LODs with a membrane diameter of 19mm at room temperature sampling were 9.2ng/L, 0.12ng/L, 0.10ng/L for limonene, cinnamaldehyde and 2-pentadecanone, respectively. Intra- and inter-membrane sampling reproducibility revealed RSD% lower than 8% and 13%, respectively. Results uniformly demonstrated that the proposed cooled membrane device could serve as an alternative powerful tool for future gas sampling.

  3. Validated UPLC-MS/MS method for simultaneous determination of simvastatin, simvastatin hydroxy acid and berberine in rat plasma: Application to the drug-drug pharmacokinetic interaction study of simvastatin combined with berberine after oral administration in rats.

    PubMed

    Liu, Mei; Su, Xianying; Li, Guofei; Zhao, Guilian; Zhao, Limei

    2015-12-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method was developed and validated for simultaneous quantification of simvastatin (SV), its metabolite simvastatin hydroxy acid (SVA) and berberine (BBR) in rat plasma. Separation was performed on Poroshell 120 EC-C18 column (4.6×50mm, 2.7μm) using gradient elution by mobile phase containing acetonitrile and 10mM ammonium acetate (pH 4.5). Polarity switch (positive-negative-positive ionization mode) was performed in a total run time of 4.0min. The lower limits of quantification (LLOQ) for SV, SVA and BBR were 0.10, 0.20 and 0.10ng/mL, respectively. The response function was established for concentration range of 0.10-100ng/mL for SV and BBR and 0.20-3000ng/mL for SVA, with a coefficient of correlation of >0.99 for all the compounds. The proposed method was applied to the drug-drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats.

  4. A UPLC-MS Method for Simultaneous Determination of Geniposidic Acid, Two Lignans and Phenolics in Rat Plasma and its Application to Pharmacokinetic Studies of Eucommia ulmoides Extract in Rats.

    PubMed

    Li, Yongjun; Gong, Zipeng; Cao, Xu; Wang, Yonglin; Wang, Aimin; Zheng, Lin; Huang, Yong; Lan, Yanyu

    2016-10-01

    The bark of Eucommia ulmoides is a well-known Chinese herbal medicine that is used to regulate blood pressure and reduce blood sugar and fats, as well as an antioxidant and antimicrobial agent. Here we describe the development of a sensitive ultrahigh performance liquid chromatography-tandem mass spectrum method for the simultaneous determination of five major active ingredients of E. ulmoides bark extract, namely, geniposidic acid (GA), protocatechuic acid (PCA), chlorogenic acid (CA), (+)-pinoresinol di-O-β-D-glucopyranoside (PDG) and (+)-pinoresinol 4'-O-β-D-glucopyranoside (PG), in rat plasma. The preliminary steps in the plasma analysis were the addition of an internal standard and acidification (0.1 % formic acid), followed by protein precipitation with methanol. Separation of the active ingredients was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm; internal diameter 1.7 µm) at a flow rate of 0.35 mL/min, with acetonitrile/water containing 0.1 % formic acid as the mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source with positive and negative ionization modes. All calibration curves showed good linearity (r ≥ 0.997) over the concentration range with the low limit of quantification between 4.45 and 54.9 ng/mL. Precision was evaluated by intra- and inter-day assays, and the percentages of the relative standard deviation were all within 15 %. Extraction efficiency and matrix effect were 84.3-102.4 % and 98.1-112.2 %, respectively. The validated method was successfully applied to the pharmacokinetic study in rats after oral administration of E. ulmoides extract. The results indicate that the pharmacokinetic properties of GA differ from those of PCA, CA, PDG and PG, respectively.

  5. 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.

  6. Highly sensitive terahertz sensor for glucose detection

    NASA Astrophysics Data System (ADS)

    Kim, Hyo-Suk; Lee, Dong-Kyu; Lee, Seok; Chung, Youngchul; Seo, Minah

    2015-07-01

    In this report, we present a new type of non-contact detection method for glucose molecule using nano antenna array based bio sensing chip that operates at terahertz frequency range (0.5 - 2.5 THz). Localized and hugely enhanced transmitted terahertz field by nano antenna array in the sensing chip induced enhancement of absorption coefficient of glucose molecule that enables us to detect even very small volume of molecules. Nano antenna based terahertz sensing chip can be expected to offer accurate identification of glucose level as a non-invasive and painless sensing tool with high sensitivity.

  7. High-sensitivity 25-micron microbolometer FPAs

    NASA Astrophysics Data System (ADS)

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

    2002-08-01

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

  8. 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.

  9. High sensitivity troponin and valvular heart disease.

    PubMed

    McCarthy, Cian P; Donnellan, Eoin; Phelan, Dermot; Griffin, Brian P; Sarano, Maurice Enriquez-; McEvoy, John W

    2017-01-16

    Blood-based biomarkers have been extensively studied in a range of cardiovascular diseases and have established utility in routine clinical care, most notably in the diagnosis of acute coronary syndrome (e.g., troponin) and the management of heart failure (e.g., brain-natriuretic peptide). The role of biomarkers is less well established in the management of valvular heart disease (VHD), in which the optimal timing of surgical intervention is often challenging. One promising biomarker that has been the subject of a number of recent VHD research studies is high sensitivity troponin (hs-cTn). Novel high-sensitivity assays can detect subclinical myocardial damage in asymptomatic individuals. Thus, hs-cTn may have utility in the assessment of asymptomatic patients with severe VHD who do not have a clear traditional indication for surgical intervention. In this state-of-the-art review, we examine the current evidence for hs-cTn as a potential biomarker in the most commonly encountered VHD conditions, aortic stenosis and mitral regurgitation. This review provides a synopsis of early evidence indicating that hs-cTn has promise as a biomarker in VHD. However, the impact of its measurement on clinical practice and VHD outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality.

  10. High-sensitivity detection of TNT.

    PubMed

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

    2006-12-26

    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 approximately 400 nm around 7.3 microm and produces a maximum continuous-wave power of approximately 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-microm region to demonstrate continuous tunability of the IR source.

  11. 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.

  12. Designation of pathogenic resistant bacteria in the Sparusaurata sea collected in Tunisia coastlines: Correlation with high performance liquid chromatography-tandem mass spectrometry analysis of antibiotics.

    PubMed

    Zouiten, Amina; Mehri, Ines; Beltifa, Asma; Ghorbel, Asma; Sire, Olivier; Van Loco, Joris; Abdenaceur, Hassen; Reyns, Tim; Ben Mansour, Hedi

    2017-01-03

    Vibrio is characterized by a large number of species and some of them are human pathogens causing gastro intestinal and wound infections through the ingestion or manipulation of contaminated fishes including Vibrio parahaemolyticus and Vibrio alginolyticus. In this study, we reported the phenotypic and molecular characterization of Vibrio parahaemolyticus and Vibrio alginolyticus strains isolated from wild and farm sea bream (Sparus aurata L.) along the Tunisian coast from December 2015 to April 2016. Therefore, the antibiograms indicate a difference between farmed and wild fish. Resistance against amoxicillin antibiotic appears for the bacteria isolated from wild fish, while those from aquaculture farming presented sensitivity to amoxicillin and resistance to antibiotics colistin and fusidic acid. The chloramphenicol antibiotic exhibited a high sensitivity in all isolated bacteria. In fact, traces of amoxicillin in the organs of the fish from Hergla farm were detected by UPLC-MS/MS analysis during December 2016 to April 2016. In addition, antibiotics were detected in January 2014 with high concentration of norfloxacin 2262 ng/g in fish from Hergla coast. The results obtained in this work indicated that the use and presence of antibiotics in water impacts on the occurrence of resistant bacteria and the detection of antibiotic in fish.

  13. 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.

  14. 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.

  15. High-sensitivity fiber optic acoustic sensors

    NASA Astrophysics Data System (ADS)

    Lu, Ping; Liu, Deming; Liao, Hao

    2016-11-01

    Due to the overwhelming advantages compared with traditional electronicsensors, fiber-optic acoustic sensors have arisen enormous interest in multiple disciplines. In this paper we present the recent research achievements of our group on fiber-optic acoustic sensors. The main point of our research is high sensitivity interferometric acoustic sensors, including Michelson, Sagnac, and Fabry-Pérot interferometers. In addition, some advanced technologies have been proposed for acoustic or acoustic pressure sensing such as single-mode/multimode fiber coupler, dual FBGs and multi-longitudinal mode fiber laser based acoustic sensors. Moreover, our attention we have also been paid on signal demodulation schemes. The intensity-based quadrature point (Q-point) demodulation, two-wavelength quadrature demodulation and symmetric 3×3 coupler methodare discussed and compared in this paper.

  16. 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.

  17. Highly sensitive silicon microreactor for catalyst testing

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

    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 3×1014 molecules s-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 μm2 are conveniently characterized with the device.

  18. 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.

  19. Transportable high sensitivity small sample radiometric calorimeter

    SciTech Connect

    Wetzel, J.R.; Biddle, R.S.; Cordova, B.S.; Sampson, T.E.; Dye, H.R.; McDow, J.G.

    1998-12-31

    A new small-sample, high-sensitivity transportable radiometric calorimeter, which can be operated in different modes, contains an electrical calibration method, and can be used to develop secondary standards, will be described in this presentation. The data taken from preliminary tests will be presented to indicate the precision and accuracy of the instrument. The calorimeter and temperature-controlled bath, at present, require only a 30-in. by 20-in. tabletop area. The calorimeter is operated from a laptop computer system using unique measurement module capable of monitoring all necessary calorimeter signals. The calorimeter can be operated in the normal calorimeter equilibration mode, as a comparison instrument, using twin chambers and an external electrical calibration method. The sample chamber is 0.75 in (1.9 cm) in diameter by 2.5 in. (6.35 cm) long. This size will accommodate most {sup 238}Pu heat standards manufactured in the past. The power range runs from 0.001 W to <20 W. The high end is only limited by sample size.

  20. 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.

  1. 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.

  2. 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.

  3. High sensitivity gas spectroscopy of porous, highly scattering solids.

    PubMed

    Svensson, Tomas; Andersson, Mats; Rippe, Lars; Johansson, Jonas; Folestad, Staffan; Andersson-Engels, Stefan

    2008-01-01

    We present minimalistic and cost-efficient instrumentation employing tunable diode laser gas spectroscopy for the characterization of porous and highly scattering solids. The sensitivity reaches 3 x 10(-6) (absorption fraction), and the improvement with respect to previous work in this field is a factor of 10. We also provide the first characterization of the interference phenomenon encountered in high-resolution spectroscopy of turbid samples. Revealing that severe optical interference originates from the samples, we discuss important implications for system design. In addition, we introduce tracking coils and sample rotation as new and efficient tools for interference suppression. The great value of the approach is illustrated in an application addressing structural properties of pharmaceutical materials.

  4. 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

  5. High Sensitivity Optomechanical Reference Accelerometer over 10 kHz

    DTIC Science & Technology

    2014-06-05

    measurements and observations in seismology and gravimetry. 2 High sensitivity optomechanical reference accele Approved for public release; distribution is...and this category of accelerometers, outlining a path for high sensitivity reference acceleration measurements and observations in seismology and...Traditional applications require either high acceleration resolution, such as in gravimetry or seismology well below 100 Hz, or large bandwidths, as for

  6. 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.

  7. 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.

  8. Achieving High Sensitivity in Cavity Optomechanical Magnetometry

    DTIC Science & Technology

    2014-03-08

    Box 12211 Research Triangle Park, NC 27709-2211 Magnetometry, cavity optomechanical sensing, photonic sensing, microfabrication REPORT DOCUMENTATION...of  experimental  set-­‐up.  FPC:   Fiber  polarization  controller.   Fig.  3  Sensitivity  as  a  function  of...function  of  signal  frequency.   Fig.  5  Photograph  of  assembled  CaF   crystal  resonator  sensor.   Fig.  6

  9. 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.

  10. Highly sensitive magnetite nano clusters for MR cell imaging.

    PubMed

    Li, Mingli; Gu, Hongchen; Zhang, Chunfu

    2012-03-31

    High sensitivity and suitable sizes are essential for magnetic iron oxide contrast agents for cell imaging. In this study, we have fabricated highly MR sensitive magnetite nanoclusters (MNCs) with tunable sizes. These clusters demonstrate high MR sensitivity. Especially, water suspensions of the MNCs with average size of 63 nm have transverse relaxivity as high as 630 s-1mM-1, which is among the most sensitive iron oxide contrast agents ever reported. Importantly, such MNCs have no adverse effects on cells (RAW 264.7). When used for cell imaging, they demonstrate much higher efficiency and sensitivity than those of SHU555A (Resovist), a commercially available contrast agent, both in vitro and in vivo, with detection limits of 3,000 and 10,000 labeled cells, respectively. The studied MNCs are sensitive for cell imaging and promising for MR cell tracking in clinics.

  11. Highly sensitive magnetite nano clusters for MR cell imaging

    PubMed Central

    2012-01-01

    High sensitivity and suitable sizes are essential for magnetic iron oxide contrast agents for cell imaging. In this study, we have fabricated highly MR sensitive magnetite nanoclusters (MNCs) with tunable sizes. These clusters demonstrate high MR sensitivity. Especially, water suspensions of the MNCs with average size of 63 nm have transverse relaxivity as high as 630 s-1mM-1, which is among the most sensitive iron oxide contrast agents ever reported. Importantly, such MNCs have no adverse effects on cells (RAW 264.7). When used for cell imaging, they demonstrate much higher efficiency and sensitivity than those of SHU555A (Resovist), a commercially available contrast agent, both in vitro and in vivo, with detection limits of 3,000 and 10,000 labeled cells, respectively. The studied MNCs are sensitive for cell imaging and promising for MR cell tracking in clinics. PMID:22462693

  12. 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.

  13. Microstructure-Sensitive Modeling of High Cycle Fatigue (Preprint)

    DTIC Science & Technology

    2009-03-01

    SUBJECT TERMS microplasticity , microstructure-sensitive modeling, high cycle fatigue, fatigue variability 16. SECURITY CLASSIFICATION OF: 17...3Air Force Research Laboratory Wright Patterson Air Force Base, Ohio 45433 Keywords: Microplasticity , microstructure-sensitive modeling, high cycle...cyclic microplasticity ) plays a key role in modeling fatigue resistance. Unlike effective properties such as elastic stiffness, fatigue is

  14. Highly linear, sensitive analog-to-digital converter

    NASA Technical Reports Server (NTRS)

    Cox, J.; Finley, W. R.

    1969-01-01

    Analog-to-digital converter converts 10 volt full scale input signal into 13 bit digital output. Advantages include high sensitivity, linearity, low quantitizing error, high resistance to mechanical shock and vibration loads, and temporary data storage capabilities.

  15. 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.

  16. Multipurpose High Sensitivity Radiation Detector: Terradex

    NASA Astrophysics Data System (ADS)

    Alpat, Behcet; Aisa, Damiano; Bizzarri, Marco; Blasko, Sandor; Esposito, Gennaro; Farnesini, Lucio; Fiori, Emmanuel; Papi, Andrea; Postolache, Vasile; Renzi, Francesca; Ionica, Romeo; Manolescu, Florentina; Ozkorucuklu, Suat; Denizli, Haluk; Tapan, Ilhan; Pilicer, Ercan; Egidi, Felice; Moretti, Cesare; Dicola, Luca

    2007-05-01

    Terradex project aims to realise an accurate and programmable multiparametric tool which will measure relevant physical quantities such as observation time, energy and type of all decay products of three naturally occurring decay chains of uranium and thorium series present in nature as well as the decay products of man-made radioactivity. The measurements described in this work are based on the performance tests of the first version of an instrument that is designed to provide high counting accuracy, by introducing self-triggering, delayed time-coincidence technique, of products of a given decay chain. In order to qualify the technique and to calibrate the Terradex, a 222Rn source is used. The continuous and accurate monitoring of radon concentration in air is realised by observing the alpha and beta particles produced by the decay of 222Rn and its daughters and tag each of them with a precise occurrence time. The validity of delayed coincident technique by using the state of the art electronics with application of novel data sampling and analysis methods are discussed. The flexibility of sampling protocols and the advantages of online calibration capability to achieve the highest level of precision in natural and man-made radiation measurements are also described.

  17. Novel ultra-high sensitive 'metal resist' for EUV lithography

    NASA Astrophysics Data System (ADS)

    Fujimori, Toru; Tsuchihashi, Toru; Minegishi, Shinya; Kamizono, Takashi; Itani, Toshiro

    2016-03-01

    This study describes the use of a novel ultra-high sensitive `metal resist' for use in extreme ultraviolet (EUV) lithography. Herein, the development of a metal resist has been studied for improving the sensitivity when using metal-containing non-chemically amplified resist materials; such materials are metal-containing organic-inorganic hybrid compounds and are referred to as EUVL Infrastructure Development Center, Inc. (EIDEC) standard metal EUV resist (ESMR). The novel metal resist's ultra-high sensitivity has previously been investigated for use with electron beam (EB) lithography. The first demonstration of ESMR performance was presented in SPIE2015, where it was shown to achieve 17-nm lines with 1.5 mJ/cm2: equivalent in EUV lithography tool. The sensitivity of ESMR using EUV open-flame exposure was also observed to have the same high sensitivity as that when using EB lithography tool. Therefore, ESMR has been confirmed to have the potential of being used as an ultra-high sensitive EUV resist material. The metal-containing organic-inorganic hybrid compounds and the resist formulations were investigated by measuring their sensitivity and line-width roughness (LWR) improvement. Furthermore, new processing conditions, such as new development and rinse procedures, are an extremely effective way of improving lithographic performance. In addition, the optimal dry-etching selective conditions between the metal resist and spin-on carbon (SOC) were obtained. The etched SOC pattern was successfully constructed from a stacked film of metal resist and SOC.

  18. Highly sensitive long-period fiber-grating strain sensor with low temperature sensitivity.

    PubMed

    Wang, Yi-Ping; Xiao, Limin; Wang, D N; Jin, Wei

    2006-12-01

    A long-period fiber-grating sensor with a high strain sensitivity of -7.6 pm/microepsilon and a low temperature sensitivity of 3.91 pm/ degrees C is fabricated by use of focused CO(2) laser beam to carve periodic grooves on a large- mode-area photonic crystal fiber. Such a strain sensor can effectively reduce the cross-sensitivity between strain and temperature, and the temperature-induced strain error obtained is only 0.5 microepsilon/ degrees C without using temperature compensation.

  19. A strategy to design highly efficient porphyrin sensitizers for dye-sensitized solar cells.

    PubMed

    Chang, Yu-Cheng; Wang, Chin-Li; Pan, Tsung-Yu; Hong, Shang-Hao; Lan, Chi-Ming; Kuo, Hshin-Hui; Lo, Chen-Fu; Hsu, Hung-Yu; Lin, Ching-Yao; Diau, Eric Wei-Guang

    2011-08-21

    We designed highly efficient porphyrin sensitizers with two phenyl groups at meso-positions of the macrocycle bearing two ortho-substituted long alkoxyl chains for dye-sensitized solar cells; the ortho-substituted devices exhibit significantly enhanced photovoltaic performances with the best porphyrin, LD14, showing J(SC) = 19.167 mA cm(-2), V(OC) = 0.736 V, FF = 0.711, and overall power conversion efficiency η = 10.17%.

  20. Highly sensitive wide bandwidth photodetectors using chemical vapor deposited graphene

    NASA Astrophysics Data System (ADS)

    Goo Kang, Chang; Kyung Lee, Sang; Jin Yoo, Tae; Park, Woojin; Jung, Ukjin; Ahn, Jinho; Hun Lee, Byoung

    2014-04-01

    A photodetector generating a nearly constant photocurrent in a very wide spectral range from ultraviolet (UV) to infrared has been demonstrated using chemical vapor deposited (CVD) graphene. Instability due to a photochemical reaction in the UV region has been minimized using an Al2O3 passivation layer, and a responsivity comparable to that of Highly Ordered Pyrolytic Graphite graphene photodetectors of ˜8 mA/W has been achieved at a 0.1 V bias, despite high defect density in the CVD graphene. A highly sensitive multi-band photodetector using graphene has many potential applications including optical interconnects, multi-band imaging sensors, highly sensitive motion detectors, etc.

  1. Approach to the Highly Sensitized Kidney Transplant Candidate.

    PubMed

    Keith, Douglas S; Vranic, Gayle M

    2016-04-07

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

  2. 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.

  3. High sensitivity cardiac troponin assays in the clinical laboratories.

    PubMed

    Jarolim, Petr

    2015-04-01

    Immunoassays measuring cardiac troponins I or T have become firmly established as critical tools for diagnosing acute myocardial infarction. While most contemporary assays provide adequate diagnostic performance, the increased sensitivity and precision of the new, high sensitivity assays that have already been introduced into clinical practice, provide the potential to further shorten intervals between blood draws or the time needed to detect the first significant troponin elevation. In addition to the relatively modest benefits at the diagnostic end, the high sensitivity assays and the investigational ultrasensitive cardiac troponin assays offer improvements for predicting major adverse cardiovascular events, development of heart failure or transition to end-stage kidney disease. These novel high sensitivity assays can measure troponin concentrations in 50%-100% of healthy individuals and therefore allow for the distribution of troponin values within a healthy cohort to be measured, patient's baseline troponin levels to be monitored, and clinicians to be alerted of deteriorating cardiorenal conditions. We envisage that the high sensitivity assays will become important tools for predicting each patient's risk of future adverse events and for guiding and monitoring corresponding adjustments of preventative therapeutic interventions.

  4. 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

    2016-06-07

    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.

  5. Highly sensitive optical sensor system for blood leakage detection

    NASA Astrophysics Data System (ADS)

    Ueda, Masahiro; Ishikawa, Kazuhiko; Jie, Chen; Sanae, Mizuno; Touma, Yasunori

    A highly sensitive method for the detection of blood leakage has been developed, and a practical sensor system for blood concentration measurement has been constructed. The present method is based on the attenuation of laser light by blood cells. The effects of the fluctuations of the incident laser light power are eliminated by normalizing the attenuated light intensity by the incident light intensity. A part of the incident laser light is reflected by a beam splitter mounted at the entrance of the test cell, of which the power is measured to provide base data for normalization. The optical path is extended to enhance sensitivity by using a pair of side mirrors. This multi-reflection method is very effective to increase sensitivity; the maximum sensitivity obtained for blood concentration is about 4 X 10 -6 by volume, which is significantly higher than that of the conventional sensors.

  6. 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

  7. Scalable photonic crystal chips for high sensitivity protein detection.

    PubMed

    Liang, Feng; Clarke, Nigel; Patel, Parth; Loncar, Marko; Quan, Qimin

    2013-12-30

    Scalable microfabrication technology has enabled semiconductor and microelectronics industries, among other fields. Meanwhile, rapid and sensitive bio-molecule detection is increasingly important for drug discovery and biomedical diagnostics. In this work, we designed and demonstrated that photonic crystal sensor chips have high sensitivity for protein detection and can be mass-produced with scalable deep-UV lithography. We demonstrated label-free detection of carcinoembryonic antigen from pg/mL to μg/mL, with high quality factor photonic crystal nanobeam cavities.

  8. An Automated High-Throughput Metabolic Stability Assay Using an Integrated High-Resolution Accurate Mass Method and Automated Data Analysis Software

    PubMed Central

    Shah, Pranav; Kerns, Edward; Nguyen, Dac-Trung; Obach, R. Scott; Wang, Amy Q.; Zakharov, Alexey; McKew, John; Simeonov, Anton; Hop, Cornelis E. C. A.

    2016-01-01

    Advancement of in silico tools would be enabled by the availability of data for metabolic reaction rates and intrinsic clearance (CLint) of a diverse compound structure data set by specific metabolic enzymes. Our goal is to measure CLint for a large set of compounds with each major human cytochrome P450 (P450) isozyme. To achieve our goal, it is of utmost importance to develop an automated, robust, sensitive, high-throughput metabolic stability assay that can efficiently handle a large volume of compound sets. The substrate depletion method [in vitro half-life (t1/2) method] was chosen to determine CLint. The assay (384-well format) consisted of three parts: 1) a robotic system for incubation and sample cleanup; 2) two different integrated, ultraperformance liquid chromatography/mass spectrometry (UPLC/MS) platforms to determine the percent remaining of parent compound, and 3) an automated data analysis system. The CYP3A4 assay was evaluated using two long t1/2 compounds, carbamazepine and antipyrine (t1/2 > 30 minutes); one moderate t1/2 compound, ketoconazole (10 < t1/2 < 30 minutes); and two short t1/2 compounds, loperamide and buspirone (t½ < 10 minutes). Interday and intraday precision and accuracy of the assay were within acceptable range (∼12%) for the linear range observed. Using this assay, CYP3A4 CLint and t1/2 values for more than 3000 compounds were measured. This high-throughput, automated, and robust assay allows for rapid metabolic stability screening of large compound sets and enables advanced computational modeling for individual human P450 isozymes. PMID:27417180

  9. Sensitization trends after renal allograft failure: the role of DQ eplet mismatches in becoming highly sensitized.

    PubMed

    Singh, Pooja; Filippone, Edward J; Colombe, Beth W; Shah, Ashesh P; Zhan, Tingting; Harach, Mary; Gorn, Chad; Frank, Adam M

    2016-01-01

    Sensitization following renal allograft failure (AF) is highly variable. Some patients remain non-sensitized (NS), while others become highly sensitized (HS). We studied 66 NS patients who experienced AF after initial kidney transplantation. Post-failure, two main groups of NS panel reactive antibody (PRA) class I and II <10% and HS patients (PRA class I or II ≥80%) were identified. The impact of acute rejection (AR), immunosuppression withdrawal (ISW) at AF, allograft nephrectomy, graft intolerance syndrome (GIS), and both standard serologic and eplet-based mismatches (MM) in inducing HS status after failure was examined. Late PRA testing post-failure revealed 18 patients remained NS and 34 patients became HS. African American recipients, ISW at AF, DQB1 eplet MM, and presence of GIS were associated with becoming HS. Presence of total zero eplet MM, zero DQA1/B1 eplet MM, continuation of immunosuppression after failure, and a hyporesponsive immune status characterized by recurrent infections were features of NS patients. DQ eplet MM represents a significant risk for becoming HS after AF. Studies comparing ISW vs. continuation in re-transplant candidates with high baseline DQ eplet MM burden should be performed. This may provide insights if sensitization post-AF can be lessened.

  10. 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.

  11. 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

  12. [Burner head with high sensitivity in atomic absorption spectroscopy].

    PubMed

    Feng, X; Yang, Y

    1998-12-01

    This paper presents a burner head with gas-sample separate entrance and double access, which is used for atomic absorption spectroscopy. According to comparison and detection, the device can improve sensitivity by a factor of 1 to 5. In the meantime it has properties of high stability and resistance to interference.

  13. 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

  14. Conjugation of selenophene with bipyridine for a high molar extinction coefficient sensitizer in dye-sensitized solar cells.

    PubMed

    Gao, Feifei; Cheng, Yueming; Yu, Qingjiang; Liu, Shi; Shi, Dong; Li, Yunhui; Wang, Peng

    2009-03-16

    A high molar extinction coefficient heteroleptic polypyridyl ruthenium sensitizer, featuring a conjugated electron-rich selenophene unit in its ancillary ligand, has been synthesized and demonstrated as an efficient sensitizer in dye-sensitized solar cells. A nanocrystalline titania film stained with this sensitizer shows improved optical absorptivity, which is highly desirable for dye-sensitized solar cells with a thin photoactive layer. With preliminary testing, this sensitizer has already achieved a high efficiency of 10.6% measured under the air mass 1.5 global conditions.

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

    USGS Publications Warehouse

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

    2007-01-01

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

  16. Highly sensitive detection using microring resonator and nanopores

    NASA Astrophysics Data System (ADS)

    Bougot-Robin, K.; Hoste, J. W.; Le Thomas, N.; Bienstman, P.; Edel, J. B.

    2016-04-01

    One of the most significant challenges facing physical and biological scientists is the accurate detection and identification of single molecules in free-solution environments. The ability to perform such sensitive and selective measurements opens new avenues for a large number of applications in biological, medical and chemical analysis, where small sample volumes and low analyte concentrations are the norm. Access to information at the single or few molecules scale is rendered possible by a fine combination of recent advances in technologies. We propose a novel detection method that combines highly sensitive label-free resonant sensing obtained with high-Q microcavities and position control in nanoscale pores (nanopores). In addition to be label-free and highly sensitive, our technique is immobilization free and does not rely on surface biochemistry to bind probes on a chip. This is a significant advantage, both in term of biology uncertainties and fewer biological preparation steps. Through combination of high-Q photonic structures with translocation through nanopore at the end of a pipette, or through a solid-state membrane, we believe significant advances can be achieved in the field of biosensing. Silicon microrings are highly advantageous in term of sensitivity, multiplexing, and microfabrication and are chosen for this study. In term of nanopores, we both consider nanopore at the end of a nanopipette, with the pore being approach from the pipette with nanoprecise mechanical control. Alternatively, solid state nanopores can be fabricated through a membrane, supporting the ring. Both configuration are discussed in this paper, in term of implementation and sensitivity.

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

    DOE PAGES

    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.

  18. A highly sensitive quantification of phytosterols through an inexpensive derivatization.

    PubMed

    Liu, Songbai; Ruan, Huina

    2013-01-01

    A highly sensitive method for quantification of phytosterols based on HPLC has been developed by derivatization with the benzoyl chromophore. Introduction of the chromophore, benzoyl group, to phytosterols via simple and inexpensive derivatization greatly improved the UV response at 254 nm. Quantification of phytosterols was effectively performed by HPLC analysis with methyl benzoate as the internal standard after derivatization. This new method demonstrated outstanding yield of recovery (> 95%) and excellent sensitivity (ng level) and was applicable for sterols from either plant or animal sources. This method is generally useful in phytosterol studies.

  19. Cardiac troponins and high-sensitivity cardiac troponin assays.

    PubMed

    Conrad, Michael J; Jarolim, Petr

    2014-03-01

    Measurement of circulating cardiac troponins I and T has become integral to the diagnosis of myocardial infarction. This article discusses the structure and function of the troponin complex and the release of cardiac troponin molecules from the injured cardiomyocyte into the circulation. An overview of current cardiac troponin assays and their classification according to sensitivity is presented. The diagnostic criteria, role, and usefulness of cardiac troponin for myocardial infarction are discussed. In addition, several examples are given of the usefulness of high-sensitivity cardiac troponin assays for short-term and long-term prediction of adverse events.

  20. 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.

  1. Ultra Broadband High Sensitivity Electro-optic Field Sensors

    NASA Astrophysics Data System (ADS)

    Wieting, Terence J.; Qadri, Syed B.; Wu, Dong Ho

    2004-03-01

    We have carried out electro-optics experiments for the development of high sensitivity EO field sensors that detect electric fields noninvasively over a very broad frequency range. Presently we have obtained a maximum field sensitivity about 2 mV/m and the sensor has been tested over the frequency range of 0.1 Hz -200 MHz. We have used various EO materials, which include LiNbO_3, (Sr,Ba)Nb_2O_6, and DAST. Currently we are testing the sensors at frequencies of 200 MHz through 50 GHz, and also improving the sensors to achieve the field sensitivity to be better than 2 μ V/m. We found that even a small variation of materials properties greatly alters the sensors characteristics. We will present detailed sensor's characteristics that are obtained with various materials' chemical and physical properties.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    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.

  3. 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.

  4. Design of highly sensitive multichannel bimetallic photonic crystal fiber biosensor

    NASA Astrophysics Data System (ADS)

    Hameed, Mohamed Farhat O.; Alrayk, Yassmin K. A.; Shaalan, Abdelhamid A.; El Deeb, Walid S.; Obayya, Salah S. A.

    2016-10-01

    A design of a highly sensitive multichannel biosensor based on photonic crystal fiber is proposed and analyzed. The suggested design has a silver layer as a plasmonic material coated by a gold layer to protect silver oxidation. The reported sensor is based on detection using the quasi transverse electric (TE) and quasi transverse magnetic (TM) modes, which offers the possibility of multichannel/multianalyte sensing. The numerical results are obtained using a finite element method with perfect matched layer boundary conditions. The sensor geometrical parameters are optimized to achieve high sensitivity for the two polarized modes. High-refractive index sensitivity of about 4750 nm/RIU (refractive index unit) and 4300 nm/RIU with corresponding resolutions of 2.1×10-5 RIU, and 2.33×10-5 RIU can be obtained according to the quasi TM and quasi TE modes of the proposed sensor, respectively. Further, the reported design can be used as a self-calibration biosensor within an unknown analyte refractive index ranging from 1.33 to 1.35 with high linearity and high accuracy. Moreover, the suggested biosensor has advantages in terms of compactness and better integration of microfluidics setup, waveguide, and metallic layers into a single structure.

  5. 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

  6. 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.

  7. 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.

  8. Quantum dots as FRET acceptors for highly sensitive multiplexing immunoassays

    NASA Astrophysics Data System (ADS)

    Geissler, Daniel; Hildebrandt, Niko; Charbonnière, Loïc J.; Ziessel, Raymond F.; Löhmannsröben, Hans-Gerd

    2009-02-01

    Homogeneous immunoassays have the benefit that they do not require any time-consuming separation steps. FRET is one of the most sensitive homogeneous methods used for immunoassays. Due to their extremely strong absorption over a broad wavelength range the use of quantum dots as FRET acceptors allows for large Foerster radii, an important advantage for assays in the 5 to 10 nm distance range. Moreover, because of their size-tunable emission, quantum dots of different sizes can be used with a single donor for the detection of different analytes (multiplexing). As the use of organic dyes with short fluorescence decay times as donors is known to be inefficient with quantum dot acceptors, lanthanide complexes with long luminescence decays are very efficient alternatives. In this contribution we present the application of commercially available biocompatible CdSe/ZnS core/shell quantum dots as multiplexing FRET acceptors together with a single terbium complex as donor in a homogeneous immunoassay system. Foerster radii of 10 nm and FRET efficiencies of 75 % are demonstrated. The high sensitivity of the terbium-toquantum dot FRET assay is shown by sub-100-femtomolar detection limits for two different quantum dots (emitting at 605 and 655 nm) within the same biotin-streptavidin assay. Direct comparison to the FRET immunoassay "gold standard" (FRET from Eu-TBP to APC) yields a three orders of magnitude sensitivity improvement, demonstrating the big advantages of quantum dots not only for multiplexing but also for highly sensitive nanoscale analysis.

  9. Sensitive and high sensitivity next generation cardiac troponin assays: more than just a name.

    PubMed

    Christenson, Robert H; Phillips, Daniel

    2011-04-01

    In the 20 years that cardiac troponin testing has been available in clinical laboratories, the biomarker has revolutionised testing of patients with acute coronary syndromes. Cardiac troponin I and T testing has become the cornerstone for diagnosis of myocardial infarction and is useful for risk assessment and management of suspected acute coronary syndrome patients. As evidence and knowledge have evolved, it has become clear that even small troponin elevations are associated with adverse health outcomes. As a result there have been several generations of troponin assays, all toward tests that reliably detect lower concentrations of this critical analyte. Guidance for cardiac troponin interpretation has been in the form of myocardial infarction redefinition and evidence-based clinical and analytical guidelines. Although terminology naming generations for cardiac troponin assays has been inconsistent, state-of-the-art cardiac troponin assays are generally referred to as 'sensitive' assays and are in general compliance with analytical guidelines. Evidence shows that use of a sensitive troponin assay can result in diagnosis of myocardial infarction earlier. Next generation cardiac troponin I and T assays will likely be termed 'high sensitivity'; these assays should have the ability to measure troponin with a CV of total error of <10% at concentrations significantly lower than the 99 percentile of the normal reference population. As such, these assays should reliably measure troponin in most normal individuals and detect troponin changes (delta values) below the 99 percentile. This property may result in earlier ACS diagnosis and better management. Utilisation of high sensitivity troponin measurements may be useful for applications other than acute coronary syndromes including risk stratifying patients with renal insufficiency, heart failure, cardiac amyloid and screening elderly patients.

  10. 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

  11. Low frequency/high sensitivity triaxial monolithic sensor

    NASA Astrophysics Data System (ADS)

    Acernese, F.; Canonico, R.; De Rosa, R.; Giordano, G.; Romano, R.; Barone, F.

    2013-04-01

    This paper describes a new mechanical implementation of a triaxial sensor, configurable as seismometer and/or as accelerometer, consisting of three one-dimensional monolithic FP sensors, suitably geometrically positioned. The triaxial sensor is, therefore, compact, light, scalable, tunable instrument (frequency < 100 mHz with large band (10-7 Hz - 10 Hz), high quality factor (Q < 1500 in air) with good immunity to environmental noises, guaranteed by an integrated laser optical readout. The measured sensitivity curve is in very good agreement with the theoretical ones (10-12m/√Hz) in the band (0.1 ÷ 10Hz). Typical applications are in the field of earthquake engineering, geophysics, civil engineering and in all applications requiring large band-low frequency performances coupled with high sensitivities.

  12. Very low frequency/high sensitivity triaxial monolithic inertial sensor

    NASA Astrophysics Data System (ADS)

    Acernese, F.; De Rosa, R.; Giordano, G.; Romano, R.; Barone, F.

    2014-03-01

    This paper describes a new mechanical implementation of a triaxial sensor, configurable as seismometer and/or as accelerometer, consisting of three one-dimensional monolithic FP sensors, suitably geometrically positioned. The triaxial sensor is, therefore, compact, light, scalable, tunable instrument (frequency < 100mHz), with large band (10-7 Hz - 10Hz), high quality factor (Q > 2500 in air) with good immunity to environmental noises, guaranteed by an integrated laser optical readout. The measured sensitivity curve is in very good agreement with the theoretical ones (10-12m/√Hz) in the band (0.1 ÷ 10Hz). Typical applications are in the field of earthquake engineering, geophysics, civil engineering and in all applications requiring large band-low frequency performances coupled with high sensitivities.

  13. Low frequency/high sensitivity triaxial monolithic inertial sensor

    NASA Astrophysics Data System (ADS)

    Acernese, F.; De Rosa, R.; Giordano, G.; Romano, Rocco; Barone, F.

    2013-10-01

    This paper describes a new mechanical implementation of a triaxial sensor, configurable as seismometer and/or as accelerometer, consisting of three one-dimensional monolithic FP sensors, suitably geometrically positioned. The triaxial sensor is, therefore, compact, light, scalable, tunable instrument (frequency < 100mHz), with large band (10-7 Hz - 10Hz), high quality factor (Q < 2500 in air) with good immunity to environmental noises, guaranteed by an integrated laser optical readout. The measured sensitivity curve is in very good agreement with the theoretical ones (10-12m/pHz) in the band (0.1 ÷ 10Hz). Typical applications are in the field of earthquake engineering, geophysics, civil engineering and in all applications requiring large band-low frequency performances coupled with high sensitivities.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Highly Sensitive Flexible Magnetic Sensor Based on Anisotropic Magnetoresistance Effect.

    PubMed

    Wang, Zhiguang; Wang, Xinjun; Li, Menghui; Gao, Yuan; Hu, Zhongqiang; Nan, Tianxiang; Liang, Xianfeng; Chen, Huaihao; Yang, Jia; Cash, Syd; Sun, Nian-Xiang

    2016-11-01

    A highly sensitive flexible magnetic sensor based on the anisotropic magnetoresistance effect is fabricated. A limit of detection of 150 nT is observed and excellent deformation stability is achieved after wrapping of the flexible sensor, with bending radii down to 5 mm. The flexible AMR sensor is used to read a magnetic pattern with a thickness of 10 μm that is formed by ferrite magnetic inks.

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

    NASA Astrophysics Data System (ADS)

    Alley, William R.; Novotny, Milos V.

    2013-06-01

    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.

  20. An early warning system for high climate sensitivity? (Invited)

    NASA Astrophysics Data System (ADS)

    Pierrehumbert, R.

    2010-12-01

    The scientific case for the clear and present danger of global warming has been unassailable at least since the release of the Charney Report more than thirty years ago, if not longer. While prompt action to begin decarbonizing energy systems could still head off much of the potential warming, it is distinctly possible that emissions will continue unabated in the coming decades, leading to a doubling or more of pre-industrial carbon dioxide concentrations. At present, we are in the unenviable position of not even knowing how bad things will get if this scenario comes to pass, because of the uncertainty in climate sensitivity. If climate sensitivity is high, then the consequences will be dire, perhaps even catastrophic. As the world continues to warm in response to continued carbon dioxide emissions, will we at least be able to monitor the climate and provide an early warning that the planet is on a high-sensitivity track, if such turns out to be the case? At what point will we actually know the climate sensitivity? It has long been recognized that the prime contributor to uncertainty in climate sensitivity is uncertainty in cloud feedbacks. Study of paleoclimate and climate of the past century has not been able to resolve which models do cloud feedback most correctly, because of uncertainties in radiative forcing. In this talk, I will discuss monitoring requirements, and analysis techniques, that might have the potential to determine which climate models most faithfully represent climate feedbacks, and thus determine which models provide the best estimate of climate sensitivity. The endeavor is complicated by the distinction between transient climate response and equilibrium climate sensitivity. I will discuss the particular challenges posed by this issue, particularly in light of recent indications that the pattern of ocean heat storage may lead to different cloud feedbacks in the transient warming stage than apply once the system has reached equilibrium. Apart

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Sensitivity to Error Fields in NSTX High Beta Plasmas

    SciTech Connect

    Park, Jong-Kyu; Menard, Jonathan E.; Gerhardt, Stefan P.; Buttery, Richard J.; Sabbagh, Steve A.; Bell, Steve E.; LeBlanc, Benoit P.

    2011-11-07

    It was found that error field threshold decreases for high β in NSTX, although the density correlation in conventional threshold scaling implies the threshold would increase since higher β plasmas in our study have higher plasma density. This greater sensitivity to error field in higher β plasmas is due to error field amplification by plasmas. When the effect of amplification is included with ideal plasma response calculations, the conventional density correlation can be restored and threshold scaling becomes more consistent with low β plasmas. However, it was also found that the threshold can be significantly changed depending on plasma rotation. When plasma rotation was reduced by non-resonant magnetic braking, the further increase of sensitivity to error field was observed.

  8. 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

  9. 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. PMID:27879841

  10. 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.

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

    PubMed

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

    2015-03-04

    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.

  12. 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.

  13. Piezoelectric rubber films for highly sensitive impact measurement

    NASA Astrophysics Data System (ADS)

    Wang, Jhih-Jhe; Tsai, Jui-Wei; Su, Yu-Chuan

    2013-07-01

    We have successfully demonstrated the microfabrication of piezoelectric rubber films and their application in impact measurement. To realize the desired piezoelectricity and stretchability, cellular polydimethylsiloxane (PDMS) structures with micrometer-sized voids are internally implanted with bipolar charges, which function as dipoles and respond promptly to electromechanical stimuli. In the prototype demonstration, 300 µm thick cellular PDMS films are fabricated and internally coated with a thin polytetrafluoroethylene (PTFE) layer to secure the implanted charges. Meanwhile, the top and bottom surfaces of the cellular PDMS films are deposited with stretchable gold electrodes. An electric field up to 35 MV m-1 is applied across the gold electrodes to ionize the air in the voids and to implant charges on the inner surfaces. The resulting composite structures behave like rubber (with an elastic modulus of about 300 kPa) and show strong piezoelectricity (with a piezoelectric coefficient d33 higher than 1000 pC N-1). While integrated with a wide bandwidth and large dynamic-range charge amplifier, highly sensitive impact measurement (with a stress sensitivity of about 10 mV Pa-1) is demonstrated. As such, the demonstrated piezoelectric rubber films could potentially serve as a sensitive electromechanical material for low-frequency stimuli, and fulfill the needs of a variety of physiological monitoring and wearable electronics applications.

  14. 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.

  15. 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.

  16. A high-sensitivity small animal SPECT system

    NASA Astrophysics Data System (ADS)

    Mitchell, Gregory S.; Cherry, Simon R.

    2009-03-01

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

  17. 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.

  18. 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

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

    PubMed

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

    2015-07-01

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

  20. 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

  1. High-sensitivity 25-μm microbolometer FPAs

    NASA Astrophysics Data System (ADS)

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

    2003-01-01

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

  2. 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.

  3. 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

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

    PubMed

    Klaus, Joseph P; Botten, Jason

    2016-03-02

    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.

  5. High Sensitivity, Low Volume Method to Determine Dissolved Phosphorus

    NASA Astrophysics Data System (ADS)

    Haberer, J. L.; Brandes, J. A.

    2001-12-01

    A high sensitivity, low volume method was developed to determine nanomolar concentrations of soluble reactive phosphorus (SRP) using reverse phase HPLC. The technique in determining SRP involved using methods from Strickland and Parsons, 1972 and Karl and Tien, 1992. Various techniques for improving blanks and sensitivity will be discussed. The method was applied to seawater and freshwater samples taken from the estuarine Nueces Delta system, Texas, two sites in the Gulf of Mexico, and within two upland (2400 m) forest catchments in the Peruvian Andes. One catchment was partially deforested within the last 3 years, while the other has remained untouched. Samples in the Gulf of Mexico were taken at a series of coastal and open water stations at various depths. Samples in each of the two upland forest catchments in Peru were obtained at 33.3 m distance intervals along a 100 m reach. Samples were taken in the Nueces River, Texas upland from a marsh estuary and from high and low regions of the marsh. Comparisons are made between the forest catchment sites in addition to comparisons made in the Nueces marsh estuary/river system. Depth profiles of SRP in the Gulf of Mexico are established. Future studies should be conducted to investigate phosphate in sediment pore waters. This method has many potential applications, is scalable across a wide range of sample volumes, and can be automated.

  6. Highly sensitive reduced graphene oxide microelectrode array sensor.

    PubMed

    Ng, Andrew M H; Kenry; Teck Lim, Chwee; Low, Hong Yee; Loh, Kian Ping

    2015-03-15

    Reduced graphene oxide (rGO) has been fabricated into a microelectrode array (MEA) using a modified nanoimprint lithography (NIL) technique. Through a modified NIL process, the rGO MEA was fabricated by a self-alignment of conducting Indium Tin Oxide (ITO) and rGO layer without etching of the rGO layer. The rGO MEA consists of an array of 10μm circular disks and microelectrode signature has been found at a pitch spacing of 60μm. The rGO MEA shows a sensitivity of 1.91nAμm(-1) to dopamine (DA) without the use of mediators or functionalization of the reduced graphene oxide (rGO) active layer. The performance of rGO MEA remains stable when tested under highly resistive media using a continuous flow set up, as well as when subjecting it to mechanical stress. The successful demonstration of NIL for fabricating rGO microelectrodes on flexible substrate presents a route for the large scale fabrication of highly sensitive, flexible and thin biosensing platform.

  7. High sensitivity micro-elastometry: applications in blood coagulopathy.

    PubMed

    Wu, Gongting; Krebs, Charles R; Lin, Feng-Chang; Wolberg, Alisa S; Oldenburg, Amy L

    2013-10-01

    Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named resonant acoustic spectroscopy with optical vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial thromboelastograph (TEG), (R = 0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5-6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150 and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood.

  8. High Sensitivity Micro-Elastometry: Applications in Blood Coagulopathy

    PubMed Central

    Wu, Gongting; Krebs, Charles R.; Lin, Feng-Chang; Wolberg, Alisa S.; Oldenburg, Amy L.

    2013-01-01

    Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named Resonant Acoustic Spectroscopy with Optical Vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial Thromboelastograph (TEG), (R=0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5–6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150% and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood. PMID:23649979

  9. Highly sensitive biosensors based on all-dielectric nanoresonators.

    PubMed

    Bontempi, Nicolò; Chong, Katie E; Orton, Henry W; Staude, Isabelle; Choi, Duk-Yong; Alessandri, Ivano; Kivshar, Yuri S; Neshev, Dragomir N

    2017-04-13

    Biosensing based on nanophotonic structures has shown a great potential for cost-efficient, high-speed and compact personal medical diagnostics. While plasmonic nanosensors offer high sensitivity, their intrinsically restricted resonance quality factors and strong heating due to metal absorption impose severe limitations on real life applications. Here, we demonstrate an all-dielectric sensing platform based on silicon nanodisks with strong optically-induced magnetic resonances, which are able to detect a concentration of streptavidin of as low as 10(-10) M (mol L(-1)) or 5 ng mL(-1), thus pushing the current detection limit by at least two orders of magnitudes. Our study suggests a new direction in biosensing based on bio-compatible, non-toxic, robust and low-loss dielectric nanoresonators with potential applications in medicine, including disease diagnosis and drug detection.

  10. Hydrophilic Packaging of Iron Oxide Nanoclusters for Highly Sensitive Imaging

    PubMed Central

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

    2015-01-01

    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−1s−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

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

    SciTech Connect

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

    1987-01-01

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

  12. Sensitivity study of reliable, high-throughput resolution metricsfor photoresists

    SciTech Connect

    Anderson, Christopher N.; Naulleau, Patrick P.

    2007-07-30

    The resolution of chemically amplified resists is becoming an increasing concern, especially for lithography in the extreme ultraviolet (EUV) regime. Large-scale screening and performance-based down-selection is currently underway to identify resist platforms that can support shrinking feature sizes. Resist screening efforts, however, are hampered by the absence of reliable resolution metrics that can objectively quantify resist resolution in a high-throughput fashion. Here we examine two high-throughput metrics for resist resolution determination. After summarizing their details and justifying their utility, we characterize the sensitivity of both metrics to two of the main experimental uncertainties associated with lithographic exposure tools, namely: limited focus control and limited knowledge of optical aberrations. For an implementation at EUV wavelengths, we report aberration and focus limited error bars in extracted resolution of {approx} 1.25 nm RMS for both metrics making them attractive candidates for future screening and down-selection efforts.

  13. Coherent Raman Scattering: Methods Towards Imaging with High Sensitivity

    NASA Astrophysics Data System (ADS)

    Bachler, Brandon Richard

    Coherent Raman spectroscopy is a powerful tool for molecular identification. For imaging applications, Raman spectroscopy techniques have offered a way of achieving endogenous chemical contrast without the need for fluorescent labeling. Increasing the sensitivity of Raman scattering microscopy is vital to performing high speed, chemically selective imaging. This thesis presents three experiments with the ultimate goal of increasing the sensitivity and quantifying limitations of different Raman techniques. The first experiment is a comparison of spontaneous and coherent Raman signal strengths under biological imaging conditions. While it is commonly stated in the literature that coherent Raman techniques provide orders of magnitude higher signal than spontaneous Raman, such a comparison has not been done under the low concentration, low excitation power conditions relevant for biological imaging. We determine a critical power above which coherent Raman methods provide higher signal and below which spontaneous Raman methods provide higher sensitivity. Contrary to what is commonly stated in the literature, spontaneous Raman can provide higher signal levels under common biological imaging conditions. The second experiment is a demonstration of the first multiplexed Raman-induced Kerr effect (BIKES) microscopy setup to date. We compare the signal-to-noise ratios between femtosecond stimulated Raman (FSRS) and RIKES for spectroscopy applications in solution and for microscopy applications with polystyrene beads. We find that for our samples, RIKES consistently provides a higher signal-to-noise ratio than FSRS for both applications. We also use RIKES microscopy to map out the distribution of cytoplasm in onion cells. Finally, a surface-enhanced Raman experiment is performed to observe and compare highly enhanced signals for spontaneous and coherent Raman spectroscopy. We use a commercial SERS substrate and observe significantly enhanced spontaneous Raman signals from

  14. Multisite comparison of high-sensitivity multiplex cytokine assays.

    PubMed

    Breen, Elizabeth Crabb; Reynolds, Sandra M; Cox, Christopher; Jacobson, Lisa P; Magpantay, Larry; Mulder, Candice B; Dibben, Oliver; Margolick, Joseph B; Bream, Jay H; Sambrano, Elise; Martínez-Maza, Otoniel; Sinclair, Elizabeth; Borrow, Persephone; Landay, Alan L; Rinaldo, Charles R; Norris, Philip J

    2011-08-01

    The concentrations of cytokines in human serum and plasma can provide valuable information about in vivo immune status, but low concentrations often require high-sensitivity assays to permit detection. The recent development of multiplex assays, which can measure multiple cytokines in one small sample, holds great promise, especially for studies in which limited volumes of stored serum or plasma are available. Four high-sensitivity cytokine multiplex assays on a Luminex (Bio-Rad, BioSource, Linco) or electrochemiluminescence (Meso Scale Discovery) platform were evaluated for their ability to detect circulating concentrations of 13 cytokines, as well as for laboratory and lot variability. Assays were performed in six different laboratories utilizing archived serum from HIV-uninfected and -infected subjects from the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) and commercial plasma samples spanning initial HIV viremia. In a majority of serum samples, interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha were detectable with at least three kits, while IL-1β was clearly detected with only one kit. No single multiplex panel detected all cytokines, and there were highly significant differences (P < 0.001) between laboratories and/or lots with all kits. Nevertheless, the kits generally detected similar patterns of cytokine perturbation during primary HIV viremia. This multisite comparison suggests that current multiplex assays vary in their ability to measure serum and/or plasma concentrations of cytokines and may not be sufficiently reproducible for repeated determinations over a long-term study or in multiple laboratories but may be useful for longitudinal studies in which relative, rather than absolute, changes in cytokines are important.

  15. Highly sensitive flow-injection chemiluminescence determination of pyrogallol compounds

    NASA Astrophysics Data System (ADS)

    Kanwal, Shamsa; Fu, Xiaohong; Su, Xingguang

    2009-12-01

    A highly sensitive flow-injection chemiluminescent method for the direct determination of pyrogallol compounds has been developed. Proposed method is based on the enhanced effect of pyrogallol compounds on the chemiluminescence signals of KMnO 4-H 2O 2 system in slightly alkaline medium. Three important pyrogallol compounds, pyrogallic acid, gallic acid and tannic acid, have been detected by this method, and the possible mechanism of the CL reaction is also discussed. The proposed method is simple, convenient, rapid (60 samples h -1), and sensitive, has a linear range of 8 × 10 -10 mol L -1 to 1 × 10 -5 mol L -1, for pyrogallic acid, with a detection limit of 6 × 10 -11 mol L -1, 4 × 10 -8 mol L -1 to 5 × 10 -3 mol L -1 for gallic acid with a detection limit of 9 × 10 -10 mol L -1, and 8 × 10 -8 mol L -1 to 5 × 10 -2 mol L -1 for tannic acid, with a detection limit of 2 × 10 -9 mol L -1, respectively. The relative standard deviation (RSD, n = 15) was 0.8, 1.1 and 1.3% for 5 × 10 -6 mol L -1 pyrogallic acid, gallic acid and tannic acid, respectively. The proposed method was successfully applied to the determination of pyrogallol compounds in tea and coffee samples.

  16. 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.

  17. New application of superconductors: High sensitivity cryogenic light detectors

    NASA Astrophysics Data System (ADS)

    Cardani, L.; Bellini, F.; Casali, N.; Castellano, M. G.; Colantoni, I.; Coppolecchia, A.; Cosmelli, C.; Cruciani, A.; D'Addabbo, A.; Di Domizio, S.; Martinez, M.; Tomei, C.; Vignati, M.

    2017-02-01

    In this paper we describe the current status of the CALDER project, which is developing ultra-sensitive light detectors based on superconductors for cryogenic applications. When we apply an AC current to a superconductor, the Cooper pairs oscillate and acquire kinetic inductance, that can be measured by inserting the superconductor in a LC circuit with high merit factor. Interactions in the superconductor can break the Cooper pairs, causing sizable variations in the kinetic inductance and, thus, in the response of the LC circuit. The continuous monitoring of the amplitude and frequency modulation allows to reconstruct the incident energy with excellent sensitivity. This concept is at the basis of Kinetic Inductance Detectors (KIDs) that are characterized by natural aptitude to multiplexed read-out (several sensors can be tuned to different resonant frequencies and coupled to the same line), resolution of few eV, stable behavior over a wide temperature range, and ease in fabrication. We present the results obtained by the CALDER collaboration with 2×2 cm2 substrates sampled by 1 or 4 Aluminum KIDs. We show that the performances of the first prototypes are already competitive with those of other commonly used light detectors, and we discuss the strategies for a further improvement.

  18. 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.

  19. Luminescent Lanthanide Reporters for High-Sensitivity Novel Bioassays.

    SciTech Connect

    Anstey, Mitchell R.; 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 "Click" 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.

  20. 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.

  1. 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.

  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. Broadband terahertz imaging with highly sensitive silicon CMOS detectors.

    PubMed

    Schuster, Franz; Coquillat, Dominique; Videlier, Hadley; Sakowicz, Maciej; Teppe, Frédéric; Dussopt, Laurent; Giffard, Benoît; Skotnicki, Thomas; Knap, Wojciech

    2011-04-11

    This paper investigates terahertz detectors fabricated in a low-cost 130 nm silicon CMOS technology. We show that the detectors consisting of a nMOS field effect transistor as rectifying element and an integrated bow-tie coupling antenna achieve a record responsivity above 5 kV/W and a noise equivalent power below 10 pW/Hz(0.5) in the important atmospheric window around 300 GHz and at room temperature. We demonstrate furthermore that the same detectors are efficient for imaging in a very wide frequency range from ~0.27 THz up to 1.05 THz. These results pave the way towards high sensitivity focal plane arrays in silicon for terahertz imaging.

  5. Magnetic probe array with high sensitivity for fluctuating field.

    PubMed

    Kanamaru, Yuki; Gota, Hiroshi; Fujimoto, Kayoko; Ikeyama, Taeko; Asai, Tomohiko; Takahashi, Tsutomu; Nogi, Yasuyuki

    2007-03-01

    A magnetic probe array is constructed to measure precisely the spatial structure of a small fluctuating field included in a strong confinement field that varies with time. To exclude the effect of the confinement field, the magnetic probes consisting of figure-eight-wound coils are prepared. The spatial structure of the fluctuating field is obtained from a Fourier analysis of the probe signal. It is found that the probe array is more sensitive to the fluctuating field with a high mode number than that with a low mode number. An experimental demonstration of the present method is attempted using a field-reversed configuration plasma, where the fluctuating field with 0.1% of the confinement field is successfully detected.

  6. High sensitivity moiré interferometry with compact achromatic interferometry

    NASA Astrophysics Data System (ADS)

    Czarnek, Robert

    Experimental observations and measurements are the sources of information essential for correct development of mathematical models of real structural materials. Moiré interferometry offers high sensitivity in full-field measurements of in-plane displacements on the surface of a specimen. Although it is a powerful method in experimental stress analysis, it has some shortcomings. One is that existing systems require highly coherent light. The only sufficient source of light for this application is a long cavity laser, which is relatively expensive and at best cumbersome. Another shortcoming is that measurements must be performed in a vibration-free environment, such as that found on a holographic table. These requirements limit the use of existing moiré interferometers to a holographic laboratory. In this paper a modified concept of compensation is presented, which permits the use of a chromatic source of light in a compact moiré system. The compensator provides order in the angles of incident light for each separate wavelength, so that the virtual reference grating created by each wavelength in a continuous spectrum is identical in frequency and spatial position. The result is a virtual reference grating that behaves exactly like that created in coherent light. With this development the use of a laser diode, which is a non-coherent light source of tiny dimensions, becomes practical. The special configuration of the optics that create the virtual grating allows its synchronization with the specimen grating and leads to an interferometer design that is relatively insensitive to the vibrations found in a mechanical testing laboratory. Sensitivity to relative motion is analyzed theoretically. This development provides the oppurtunity to apply moiré interferometry to solid mechanics problems that cannot be studied in an optics laboratory. Experimental verification of the optical concepts is provided. A compact moiré interferometer based on the presented idea was

  7. High-sensitivity (25-um pitch) microbolometer FPAs

    NASA Astrophysics Data System (ADS)

    Murphy, Daniel F.; Ray, Michael; Wyles, Richard; Asbrock, James F.; Lum, Nancy A.; Kennedy, Adam; Wyles, Jessica; Hewitt, C.; Graham, Glen E.; Horikiri, Tad; Anderson, John S.; Bradley, Daryl; Chin, Richard; Kostrzewa, Thomas

    2001-11-01

    RIO has achieved a significant technical breakthrough in uncooled FPAs by reducing the pixel size by a factor of two while maintaining state-of-the-art sensitivity. Raytheon has produced high-quality 320 by 240 micro bolometer FPAs with 25 micrometers pitch pixels. The 320 by 240 FPAs have a sensitivity that is comparable to micro bolometer FPAs with 50 micrometers pixels. The average NETD value for these FPAs is about 35 mK with an f/1 aperture and operating at 30 Hz frame rates. Good pixel operability and excellent image quality have been demonstrated. Pixel operability is greater than 99 percent on some FPAs, and uncorrected responsivity nonuniformity is less than 4 percent. The micro bolometer detectors also have a relatively fast thermal time constant of approximately 10 msec. This state-of-the-art performance has been achieved as a result of an advanced micromachining fabrication process. The process allows maximization of both the thermal isolation and the optical fill-factor. The reduction in pixel size offers several potential benefits for IR systems. For a given system resolution requirement, the 225 micrometers pixels allow a factor of two reduction in both the focal length and aperture size of the sensor optics. The pixel size reduction facilitates a significant FPA cost reduction since the number of die printed on a wafer can be increased. The pixel size reduction has enabled the development of a large-format 640 by 512 FPA array applicable to wide-field-of-view, long range surveillance and targeting missions, and a 160 by 128 array where applications for miniaturization and temperature invariance are required as well as low cost and low power.

  8. 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.

  9. A new, sensitive, high resolution Raman detector based on ionization

    NASA Astrophysics Data System (ADS)

    Smith, B. W.; Omenetto, N.; Winefordner, J. D.

    1989-01-01

    A novel detection method for weak pulsed or cw Raman fluxes is described. The detector is based upon the production of Raman scatter with a tunable pulsed or cw dye laser, collecting a large fraction of the Raman scatter and transferring it efficiently into an ionization detector containing a metal (M) vapor, such as Li. The resonance ionization detector (RID) is simultaneously illuminated by a second dye laser. When the second laser is tuned to an excited state transition of the metal vapor M and when the first laser is at such a wavelength that the Raman scatter appears at the ground state absorption transition of the metal, then a current will be produced in the RID which is proportional to the Raman scatter intensity. Both the production and collection of this current can be made very efficient (approaching 100%) and should result in improved sensitivity compared to conventional dispersive or FT Raman techniques. The new approach should be much less sensitive to scatter, should have a spectral resolution better than 0.1 cm -1 and should allow Raman scatter measurements to be made at wavenumbers below 100 cm -1 and under certain conditions to 0.01 cm -1. The approach should be especially useful in highly scattering environments like Ag-sols in surface enhanced Raman and should be useful for detection of ultratrace levels of drugs and metabolites in biological fluids. The Raman-RID approach should also be useful for resonance Raman since laser scatter and molecular fluorescence should have minimal effects.

  10. 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.

  11. 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

  12. 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

  13. Comparing standard Bonner spheres and high-sensitivity Bonner cylinders.

    PubMed

    Lee, Kuo-Wei; Yuan, Ming-Chen; Jiang, Shiang-Huei; Sheu, Rong-Jiun

    2014-10-01

    Standard Bonner spheres and proposed high-sensitivity Bonner cylinders were calibrated in a neutron calibration room, using a (252)Cf source. The Bonner sphere system consists of 11 polyethylene (PE) spheres of various diameters and 4 extended spheres that comprise embedded metal shells. Similar to the design of Bonner spheres, a set of Bonner cylinders was assembled using a large cylindrical (3)He tube as the central probe, which was wrapped using various thicknesses of PE. A layer of lead was employed inside one of the PE cylinders to increase the detection efficiency of high-energy neutrons. The central neutron probe used in the Bonner cylinders exhibited an efficiency of ∼17.9 times higher than that of the Bonner spheres. However, compared with the Bonner spheres, the Bonner cylinders are not fully symmetric in their geometry, exhibiting angular dependence in their responses to incoming neutrons. Using a series of calculations and measurements, this study presents a systematic comparison between Bonner spheres and cylinders in terms of their response functions, detection efficiencies, angular dependences and spectrum unfolding.

  14. Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks.

    PubMed

    Arampatzis, Georgios; Katsoulakis, Markos A; Pantazis, Yannis

    2015-01-01

    Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially) sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in "sloppy" systems. In particular, the computational acceleration is quantified by the ratio between the total number of parameters over the

  15. 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

  16. Simple and sensitive determination of hydrazine in drinking water by ultra-high-performance liquid chromatography-tandem mass spectrometry after derivatization with naphthalene-2,3-dialdehyde.

    PubMed

    Oh, Jin-Aa; Shin, Ho-Sang

    2015-05-22

    An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine the level of hydrazine in drinking water. The method is based on the derivatization of hydrazine with naphthalene-2,3-dicarboxaldehyde (NDA) in water. The optimum conditions for UPLC-MS/MS detection were determined as follows: derivatization reagent dosage, 50mg/L of NDA; pH 2; and reaction time, 1min; room temperature. The formed derivative was injected into an LC system without extraction or purification procedures. Under the established conditions, the method was used to detect hydrazine in raw drinking water and chlorinated drinking water. The limits of detection and quantification for hydrazine in drinking water were 0.003μg/L and 0.01μg/L, respectively. The accuracy was in the range of 97-104%, and precision, expressed as relative standard deviation, was less than 9% in drinking water. Hydrazine was detected at a concentration of 0.13μg/L in one sample among 24 raw drinking water samples and in a range of 0.04-0.45μg/L in three samples among 24 chlorinated drinking water samples.

  17. Characterization of three high efficiency and blue sensitive silicon photomultipliers

    NASA Astrophysics Data System (ADS)

    Otte, Adam Nepomuk; Garcia, Distefano; Nguyen, Thanh; Purushotham, Dhruv

    2017-02-01

    We report about the optical and electrical characterization of three high efficiency and blue sensitive Silicon photomultipliers from FBK, Hamamatsu, and SensL. Key features of the tested devices when operated at 90% breakdown probability are peak photon detection efficiencies between 40% and 55%, temperature dependencies of gain and PDE that are less than 1%/°C, dark rates of ∼50 kHz/mm2 at room temperature, afterpulsing of about 2%, and direct optical crosstalk between 6% and 20%. The characteristics of all three devices impressively demonstrate how the Silicon-photomultiplier technology has improved over the past ten years. It is further demonstrated how the voltage and temperature characteristics of a number of quantities can be parameterized on the basis of physical models. The models provide a deeper understanding of the device characteristics over a wide bias and temperature range. They also serve as examples how producers could provide the characteristics of their SiPMs to users. A standardized parameterization of SiPMs would enable users to find the optimal SiPM for their application and the operating point of SiPMs without having to perform measurements thus significantly reducing design and development cycles.

  18. Ultra-high sensitivity imaging of cancer using SERRS nanoparticles

    NASA Astrophysics Data System (ADS)

    Kircher, Moritz F.

    2016-05-01

    "Surface-enhanced Raman spectroscopy" (SERS) nanoparticles have gained much attention in recent years for in silico, in vitro and in vivo sensing applications. Our group has developed novel generations of biocompatible "surfaceenhanced resonance Raman spectroscopy" (SERRS) nanoparticles as novel molecular imaging agents. Via rigorous optimization of the different variables contributing to the Raman enhancement, we were able to design SERRS nanoparticles with so far unprecedented sensitivity of detection under in vivo imaging conditions (femto-attomolar range). This has resulted in our ability to visualize, with a single nanoparticle, many different cancer types (after intravenous injection) in mouse models. The cancer types we have tested so far include brain, breast, esophagus, stomach, pancreas, colon, sarcoma, and prostate cancer. All mouse models used are state-of-the-art and closely mimic the tumor biology in their human counterparts. In these animals, we were able to visualize not only the bulk tumors, but importantly also microscopic extensions and locoregional satellite metastases, thus delineating for the first time the true extent of tumor spread. Moreover, the particles enable the detection of premalignant lesions. Given their inert composition they are expected to have a high chance for clinical translation, where we envision them to have an impact in various scenarios ranging from early detection, image-guidance in open or minimally invasive surgical procedures, to noninvasive imaging in conjunction with spatially offset (SESORS) Raman detection devices.

  19. 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.

  20. High-sensitivity immunoassay using a novel upconverting phosphor reporter

    NASA Astrophysics Data System (ADS)

    Wright, William H.; Mufti, Naheed A.; Tagg, N. Troy; Webb, Robert R.; Schneider, Luke V.

    1997-05-01

    A new class of reporter label, consisting of rare earth elements embedded in a crystalline particle, has been developed for in vitro diagnostic applications. These unique labels upconvert low energy (IR) radiation to high energy light by a multiphoton absorption process and subsequent phosphorescence emission. As a result, upconverting phosphors can be visualized with no biological background or autofluorescence signal. In addition, phosphors have narrow absorption and emission bands, making them ideal for simultaneous multianalyte test. The crystalline nature of the phosphors makes them insensitive to environmental conditions, with essentially infinite shelf life and no photobleaching at the irradiances used for excitation. We have covalently coupled (Y0.86Yb0.08Er0.06)6O2S phosphor labels to antibody probes to create a reporter reagent that can be excited by 980 nm radiation from a diode laser and detected by a modified spectrofluorimeter. Target analyte sensitivities of approximately 10 ng/mL to Staphylococcal enterotoxin B have been demonstrated using a sandwich assay in a magnetic bead or capillary wick formats in a non-optimized assay system. These results are directly applicable to the development of assays that can be performed on microfabricated biochips or in microflow channels.

  1. High Speed Pressure Sensitive Paint for Dynamic Testing

    NASA Astrophysics Data System (ADS)

    Pena, Carolina; Chism, Kyle; Hubner, Paul

    2016-11-01

    Pressure sensitive paint (PSP) allows engineers to obtain accurate, high-spatial-resolution measurements of pressure fields over a structure. The pressure is directly related to the luminescence emitted by the paint due to oxygen quenching. Fast PSP has a higher surface area due to its porosity compared to conventional PSP, which enables faster diffusion and measurements to be acquired three orders of magnitude faster than with conventional PSP. A fast time response is needed when testing vibrating structures due to fluid-structure interaction. The goal of this summer project was to set-up, test and analyze the pressure field of an impinging air jet on a vibrating cantilever beam using Fast PSP. Software routines were developed for the processing of the emission images, videos of a static beam coated with Fast PSP were acquired with the air jet on and off, and the intensities of these two cases were ratioed and calibrated to pressure. Going forward, unsteady pressures on a vibrating beam will be measured and presented. Eventually, the long-term goal is to integrate luminescent pressure and strain measurement techniques, simultaneously using Fast PSP and a luminescent photoelastic coating on vibrating structures. Funding from NSF REU site Grant EEC 1358991 is greatly appreciated.

  2. A highly sensitive and multiplexed method for focused transcript analysis.

    PubMed

    Kataja, Kari; Satokari, Reetta M; Arvas, Mikko; Takkinen, Kristiina; Söderlund, Hans

    2006-10-01

    We describe a novel, multiplexed method for focused transcript analysis of tens to hundreds of genes. In this method TRAC (transcript analysis with aid of affinity capture) mRNA targets, a set of amplifiable detection probes of distinct sizes and biotinylated oligo(dT) capture probe are hybridized in solution. The formed sandwich hybrids are collected on magnetic streptavidin-coated microparticles and washed. The hybridized probes are eluted, optionally amplified by a PCR using a universal primer pair and detected with laser-induced fluorescence and capillary electrophoresis. The probes were designed by using a computer program developed for the purpose. The TRAC method was adapted to 96-well format by utilizing an automated magnetic particle processor. Here we demonstrate a simultaneous analysis of 18 Saccharomyces cerevisiae transcripts from two experimental conditions and show a comparison with a qPCR system. The sensitivity of the method is significantly increased by the PCR amplification of the hybridized and eluted probes. Our data demonstrate a bias-free use of at least 16 cycles of PCR amplification to increase probe signal, allowing transcript analysis from 2.5 ng of the total mRNA sample. The method is fast and simple and avoids cDNA conversion. These qualifications make it a potential, new means for routine analysis and a complementing method for microarrays and high density chips.

  3. Highly sensitive NIR PtSi/Si-nanostructure detectors

    NASA Astrophysics Data System (ADS)

    Li, Hua-gao; Guo, Pei; Yuan, An-bo; Long, Fei; Li, Rui-zhi; Li, Ping; Li, Yi

    2016-10-01

    We report a high external quantum efficiency (EQE) photodiode detector with PtSi/Si-nanostructures. Black silicon nanostructures were fabricated by metal-assist chemical etching (MCE), a 2 nm Pt layer was subsequently deposited on black silicon surface by DC magnetron sputtering system, and PtSi/Si-nanostructures were formed in vacuum annealing at 450 oC for 5 min. As the PtSi/Si-nanostructures presented a spiky shape, the absorption of incident light was remarkably enhanced for the repeat reflection and absorption. The breakdown voltage, dark current, threshold voltage and responsivity of the device were investigated to evaluate the performance of the PtSi/Si-nanostructures detector. The threshold voltage and dark currents of the PtSi/Si-nanostructure photodiode tends to be slightly higher than those of the standard diodes. The breakdown voltage remarkably was reduced because of existing avalanche breakdown in PtSi/Si-nanostructures. However, the photodiodes had high response at room temperature in near infrared region. At -5 V reverse bias voltage, the responsivity was 0.72 A/W in 1064 nm wavelength, and the EQE was 83.9%. By increasing the reverse bias voltage, the responsivity increased. At -60 V reverse bias voltage, the responsivity was 3.5 A/W, and the EQE was 407.5%, which means the quantum efficiency of PtSi/Si-nanostructure photodiodes was about 10 times higher than that of a standard diode. Future research includes how to apply this technology to enhance the NIR sensitivity of image sensors, such as Charge Coupled Devices (CCD).

  4. 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).

  5. Proposed Ultra-High Sensitivity High-Frequency Gravitational Wave Detector

    NASA Astrophysics Data System (ADS)

    Baker, Robert M. L.; Stephenson, Gary V.; Li, Fangyu

    2008-01-01

    The paper discusses the proposed improvement of a High-Frequency Relic Gravitational Wave (HFRGW) detector designed by Li, Baker, Fang, Stephenson and Chen in order to greatly improve its sensitivity. The improved detector is inspired by the Laser Interferometer Gravitational Observatory or LIGO, but is sensitive to the high-frequency end of the gravitational-wave spectrum. As described in prior papers it utilizes the Gertsenshtein effect, which introduces the conversion of gravitational waves to electromagnetic (EM) waves in the presence of a static magnetic field. Such a conversion, if it leads to photons moving in a direction perpendicular to the plane of the EM waves and the magnetic field, will allow for ultra-high sensitivity HFRGW detection. The use of sensitive microwave, single photon detectors such as a circuit QED and/or the Rydberg Atom Cavity Detector, or off-the-shelf detectors, could lead to such detection. When the EM-detection photons are focused at the microwave detectors by fractal-membrane reflectors sensitivity is also improved. Noise sources external to the HFRGW detector will be eliminated by placing a tight mosaic of superconducting tiles (e.g., YBCO) and/or fractal membranes on the interior surface of the detector's cryogenic containment vessel in order to provide a perfect Faraday cage. Internal thermal noise will be eliminated by means of a microwave absorbing (or reflecting) interior enclosure shaped to conform to a high-intensity continuous microwave Gaussian beam (GB), will reduce any background photon flux (BPF) noise radiated normal to the GB's axis. Such BPF will be further attenuated by a series of microwave absorbing baffles forming tunnels to the sensitive microwave detectors on each side of the GB and at right angles to the static magnetic field. A HFGW detector of bandwidth of 1 KHz to 10 KHz or less in the GHz band has been selected. It is concluded that the utilization of the new ultra-high-sensitivity microwave detectors

  6. A high sensitive fiber-optic strain sensor with tunable temperature sensitivity for temperature-compensation measurement

    NASA Astrophysics Data System (ADS)

    Hu, Jie; Huang, Hui; Bai, Min; Zhan, Tingting; Yang, Zhibo; Yu, Yan; Qu, Bo

    2017-02-01

    A high sensitive fiber-optic strain sensor, which consists of a cantilever, a tandem rod and a fiber collimator, was proposed. The tandem rod, which transfer the applied strain to the cantilever, was used for tuning the temperature sensitivity from ‑0.15 to 0.19 dB/°C via changing the length ratio of the rods. Moreover, due to the small beam divergence of the collimator, high strain sensitivity can be realized via incident-angle sensitive detection-mechanism. A strain detection-range of 1.1 × 103 με (with a sensing length of 21.5 mm), a detection limit of 5.7 × 10‑3 με, and a maximum operating frequency of 1.18 KHz were demonstrated. This sensor is promising for compensating the thermal-expansion of various target objects.

  7. 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.

  8. 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.

  9. Very high polarimetric sensitivity to strain of second order mode of highly birefringent microstructured fibre

    NASA Astrophysics Data System (ADS)

    Nasilowski, Tomasz; Skorupski, Krzysztof; Makara, Mariusz; Statkiewicz-Barabach, Gabriela; Mergo, Pawel; Marc, Pawel; Jaroszewicz, Leszek

    2011-05-01

    Microstructured fibres (MSF) or photonic crystal fibres (PCF) possess a number of unique properties enabling a wide range of novel applications either in the telecommunication or in the sensing domain. In this paper we show that highly birefringent (HB) MSF with a dedicated design that allows inscribing fibre Bragg gratings in the MSF core can serve as pressure or stress transducers with extremely large sensitivity of second order mode, while exhibiting a low sensitivity to temperature drifts. Therefore, Bragg gratings inscribed in such MSF may offer a viable alternative to traditional optical fibre sensors of much lower stress sensitivity that require temperature compensation mechanisms and that are not intrinsically capable of distinguishing stress and temperature.

  10. 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.

  11. High sensitivity imaging Thomson scattering for low temperature plasma

    SciTech Connect

    Meiden, H. J. van der; Al, R. S.; Barth, C. J.; Donne, A. J. H.; Goedheer, W. J.; Groot, B. de; Koppers, W. R.; Pol, M. J. van de; Prins, P. R.; Shumack, A. E.; Smeets, P. H. M.; Vijvers, W. A. J.; Westerhout, J.; Wright, G. M.; Rooij, G. J. van; Engeln, R.; Kleyn, A. W.; Lopes Cardozo, N. J.; Schram, D. C.

    2008-01-15

    A highly sensitive imaging Thomson scattering system was developed for low temperature (0.1-10 eV) plasma applications at the Pilot-PSI linear plasma generator. The essential parts of the diagnostic are a neodymium doped yttrium aluminum garnet laser operating at the second harmonic (532 nm), a laser beam line with a unique stray light suppression system and a detection branch consisting of a Littrow spectrometer equipped with an efficient detector based on a ''Generation III'' image intensifier combined with an intensified charged coupled device camera. The system is capable of measuring electron density and temperature profiles of a plasma column of 30 mm in diameter with a spatial resolution of 0.6 mm and an observational error of 3% in the electron density (n{sub e}) and 6% in the electron temperature (T{sub e}) at n{sub e}=4x10{sup 19} m{sup -3}. This is achievable at an accumulated laser input energy of 11 J (from 30 laser pulses at 10 Hz repetition frequency). The stray light contribution is below 9x10{sup 17} m{sup -3} in electron density equivalents by the application of a unique stray light suppression system. The amount of laser energy that is required for a n{sub e} and T{sub e} measurement is 7x10{sup 20}/n{sub e} J, which means that single shot measurements are possible for n{sub e}>2x10{sup 21} m{sup -3}.

  12. 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.

  13. 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.

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

    PubMed

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

    2010-01-15

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

  15. 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.

  16. 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

  17. Highly sensitive recognition element based on birefringent porous silicon layers

    NASA Astrophysics Data System (ADS)

    Gross, E.; Kovalev, D.; Künzner, N.; Timoshenko, V. Yu.; Diener, J.; Koch, F.

    2001-10-01

    Anisotropically nanostructured silicon layers exhibit a strong in-plane birefringence. Their optical anisotropy parameters are found to be extremely sensitive to the presence of dielectric substances inside of the pores. Polarization-resolved transmittance measurements provide an extremely sensitive tool to analyze the adsorption of various atoms and molecules in negligible quantities. A variation of the transmitted linearly polarized light intensity up to two orders of magnitude combined with a fast optical response in the range of seconds make these layers a good candidate for sensor applications.

  18. 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.

  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. 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)

  1. Sensitive, high-strain, high-rate bodily motion sensors based on graphene-rubber composites.

    PubMed

    Boland, Conor S; Khan, Umar; Backes, Claudia; O'Neill, Arlene; McCauley, Joe; Duane, Shane; Shanker, Ravi; Liu, Yang; Jurewicz, Izabela; Dalton, Alan B; Coleman, Jonathan N

    2014-09-23

    Monitoring of human bodily motion requires wearable sensors that can detect position, velocity and acceleration. They should be cheap, lightweight, mechanically compliant and display reasonable sensitivity at high strains and strain rates. No reported material has simultaneously demonstrated all the above requirements. Here we describe a simple method to infuse liquid-exfoliated graphene into natural rubber to create conducting composites. These materials are excellent strain sensors displaying 10(4)-fold increases in resistance and working at strains exceeding 800%. The sensitivity is reasonably high, with gauge factors of up to 35 observed. More importantly, these sensors can effectively track dynamic strain, working well at vibration frequencies of at least 160 Hz. At 60 Hz, we could monitor strains of at least 6% at strain rates exceeding 6000%/s. We have used these composites as bodily motion sensors, effectively monitoring joint and muscle motion as well and breathing and pulse.

  2. High-speed high-sensitivity infrared spectroscopy using mid-infrared swept lasers (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Childs, David T. D.; Groom, Kristian M.; Hogg, Richard A.; Revin, Dmitry G.; Cockburn, John W.; Rehman, Ihtesham U.; Matcher, Stephen J.

    2016-03-01

    Infrared spectroscopy is a highly attractive read-out technology for compositional analysis of biomedical specimens because of its unique combination of high molecular sensitivity without the need for exogenous labels. Traditional techniques such as FTIR and Raman have suffered from comparatively low speed and sensitivity however recent innovations are challenging this situation. Direct mid-IR spectroscopy is being speeded up by innovations such as MEMS-based FTIR instruments with very high mirror speeds and supercontinuum sources producing very high sample irradiation levels. Here we explore another possible method - external cavity quantum cascade lasers (EC-QCL's) with high cavity tuning speeds (mid-IR swept lasers). Swept lasers have been heavily developed in the near-infrared where they are used for non-destructive low-coherence imaging (OCT). We adapt these concepts in two ways. Firstly by combining mid-IR quantum cascade gain chips with external cavity designs adapted from OCT we achieve spectral acquisition rates approaching 1 kHz and demonstrate potential to reach 100 kHz. Secondly we show that mid-IR swept lasers share a fundamental sensitivity advantage with near-IR OCT swept lasers. This makes them potentially able to achieve the same spectral SNR as an FTIR instrument in a time x N shorter (N being the number of spectral points) under otherwise matched conditions. This effect is demonstrated using measurements of a PDMS sample. The combination of potentially very high spectral acquisition rates, fundamental SNR advantage and the use of low-cost detector systems could make mid-IR swept lasers a powerful technology for high-throughput biomedical spectroscopy.

  3. 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.

  4. Highly sensitive detection using Herriott cell for laser absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhao, Chongyi; Song, Guangming; Du, Yang; Zhao, Xiaojun; Wang, Wenju; Zhong, Liujun; Hu, Mai

    2016-11-01

    The tunable diode laser absorption spectroscopy combined with the long absorption path technique is a significant method to detect harmful gas. The long optical path could come true by Herriott cell reducing the size of the spectrometers. A 15 cm long Herriott cell with 28.8 m optical absorption path after 96 times reflection was designed that enhanced detection sensitivity of absorption spectroscopy. According to the theory data of calculation, Herriott cell is analyzed and simulated by softwares Matlab and Lighttools.

  5. Adaptive interferometry for high sensitivity optical fiber sensing

    NASA Astrophysics Data System (ADS)

    Peigné, A.; Bortolozzo, U.; Residori, S.; Molin, S.; Dolfi, D.; Huignard, J.-P.

    2015-09-01

    We report on the use of an adaptive holographic interferometer, based on a liquid crystal light valve, to achieve phase shift measurements in an optical fiber. Owing to the physical mechanisms involved, the interferometer adapts itself to slow phase variations. As a consequence, it is possible to use a multimode fiber for sensing, which improves the sensitivity. Moreover, a distributed architecture relying on phase-OTDR principle is presented and a localization experiment is performed.

  6. The strain-rate sensitivity of high-strength high-toughness steels.

    SciTech Connect

    Dilmore, M.F.; Crenshaw, Thomas B.; Boyce, Brad Lee

    2006-01-01

    The present study examines the strain-rate sensitivity of four high strength, high-toughness alloys at strain rates ranging from 0.0002 s-1 to 200 s-1: Aermet 100, a modified 4340, modified HP9-4-20, and a recently developed Eglin AFB steel alloy, ES-1c. A refined dynamic servohydraulic method was used to perform tensile tests over this entire range. Each of these alloys exhibit only modest strain-rate sensitivity. Specifically, the strain-rate sensitivity exponent m, is found to be in the range of 0.004-0.007 depending on the alloy. This corresponds to a {approx}10% increase in the yield strength over the 7-orders of magnitude change in strain-rate. Interestingly, while three of the alloys showed a concominant {approx}3-10% drop in their ductility with increasing strain-rate, the ES1-c alloy actually exhibited a 25% increase in ductility with increasing strain-rate. Fractography suggests the possibility that at higher strain-rates ES-1c evolves towards a more ductile dimple fracture mode associated with microvoid coalescence.

  7. High-performance and high-sensitivity applications of graphene transistors with self-assembled monolayers.

    PubMed

    Yeh, Chao-Hui; Kumar, Vinod; Moyano, David Ricardo; Wen, Shao-Hsuan; Parashar, Vyom; Hsiao, She-Hsin; Srivastava, Anchal; Saxena, Preeti S; Huang, Kun-Ping; Chang, Chien-Chung; Chiu, Po-Wen

    2016-03-15

    Charge impurities and polar molecules on the surface of dielectric substrates has long been a critical obstacle to using graphene for its niche applications that involve graphene's high mobility and high sensitivity nature. Self-assembled monolayers (SAMs) have been found to effectively reduce the impact of long-range scatterings induced by the external charges. Yet, demonstrations of scalable device applications using the SAMs technique remains missing due to the difficulties in the device fabrication arising from the strong surface tension of the modified dielectric environment. Here, we use patterned SAM arrays to build graphene electronic devices with transport channels confined on the modified areas. For high-mobility applications, both rigid and flexible radio-frequency graphene field-effect transistors (G-FETs) were demonstrated, with extrinsic cutoff frequency and maximum oscillation frequency enhanced by a factor of ~2 on SiO2/Si substrates. For high sensitivity applications, G-FETs were functionalized by monoclonal antibodies specific to cancer biomarker chondroitin sulfate proteoglycan 4, enabling its detection at a concentration of 0.01 fM, five orders of magnitude lower than that detectable by a conventional colorimetric assay. These devices can be very useful in the early diagnosis and monitoring of a malignant disease.

  8. 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.

  9. Analysis of Cyberbullying Sensitivity Levels of High School Students and Their Perceived Social Support Levels

    ERIC Educational Resources Information Center

    Akturk, Ahmet Oguz

    2015-01-01

    Purpose: The purpose of this paper is to determine the cyberbullying sensitivity levels of high school students and their perceived social supports levels, and analyze the variables that predict cyberbullying sensitivity. In addition, whether cyberbullying sensitivity levels and social support levels differed according to gender was also…

  10. 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.

  11. 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

  12. Development of a high sensitive MEMS hydrophone using PVDF

    NASA Astrophysics Data System (ADS)

    Varadan, Vijay K.; Zhu, Bei; K. A, Jose

    2002-05-01

    The design and experimental evaluation of a PVDF-based MEMS hydrophone is presented in this paper. The basic structure of the hydrophone was fabricated on a silicon wafer using standard NMOS process technology. A MOSFET with extended gate electrode was designed as the interface circuit to the sensing material, which is a piezoelectric polymer, polyvinylidene difluoride (PVDF). Acoustic impedance possessed by this piezoelectric material provides a reasonable match to water, which makes it very attractive for underwater applications. The electrical signal generated by the PVDF film was directly coupled to the gate of the MOSFET. To minimize the parasitic capacitance underneath the PVDF film and hence improve the device sensitivity, a thick photoresist was first employed as the dielectric layer under the extended gate electrode. For underwater operation, a waterproof Rho-C rubber encapsulated the hydrophone. A silicon nitride layer passivated the active device, which is a good barrier material to most mobile ions and solvents. The device after passivation also shows a lower noise level. The theoretical model developed to predict the sensitivity of the hydrophone shows a reasonable agreement between the theory and the experiment.

  13. Platinum decorated carbon nanotubes for highly sensitive amperometric glucose sensing

    NASA Astrophysics Data System (ADS)

    Xie, Jining; Wang, Shouyan; Aryasomayajula, L.; Varadan, V. K.

    2007-02-01

    Fine platinum nanoparticles (1-5 nm in diameter) were deposited on functionalized multi-walled carbon nanotubes (MWNTs) through a decoration technique. A novel type of enzymatic Pt/MWNTs paste-based mediated glucose sensor was fabricated. Electrochemical measurements revealed a significantly improved sensitivity (around 52.7 µA mM-1 cm-2) for glucose sensing without using any picoampere booster or Faraday cage. In addition, the calibration curve exhibited a good linearity in the range of 1-28 mM of glucose concentration. Transmission electron microscopy (TEM) and x-ray photoelectron spectroscopy (XPS) were performed to investigate the nanoscale structure and the chemical bonding information of the Pt/MWNTs paste-based sensing material, respectively. The improved sensitivity of this novel glucose sensor could be ascribed to its higher electroactive surface area, enhanced electron transfer, efficient enzyme immobilization, unique interaction in nanoscale and a synergistic effect on the current signal from possible multi-redox reactions.

  14. High-throughput, high-sensitivity analysis of gene expression in Arabidopsis.

    PubMed

    Kris, Richard Martin; Felder, Stephen; Deyholos, Michael; Lambert, Georgina M; Hinton, James; Botros, Ihab; Martel, Ralph; Seligmann, Bruce; Galbraith, David W

    2007-07-01

    High-throughput gene expression analysis of genes expressed during salt stress was performed using a novel multiplexed quantitative nuclease protection assay that involves customized DNA microarrays printed within the individual wells of 96-well plates. The levels of expression of the transcripts from 16 different genes were quantified within crude homogenates prepared from Arabidopsis (Arabidopsis thaliana) plants also grown in a 96-well plate format. Examples are provided of the high degree of reproducibility of quantitative dose-response data and of the sensitivity of detection of changes in gene expression within limiting amounts of tissue. The lack of requirement for RNA purification renders the assay particularly suited for high-throughput gene expression analysis and for the discovery of novel chemical compounds that specifically modulate the expression of endogenous target genes.

  15. Advanced Cd(II) complexes as high efficiency co-sensitizers for enhanced dye-sensitized solar cell performance.

    PubMed

    Gao, Song; Fan, Rui Qing; Wang, Xin Ming; Qiang, Liang Sheng; Wei, Li Guo; Wang, Ping; Yang, Yu Lin; Wang, Yu Lei

    2015-11-07

    This work reports on two new complexes with the general formula [Cd3(IBA)3(Cl)2(HCOO)(H2O)]n (1) and {[Cd1.5(IBA)3(H2O)6]·3.5H2O}n (2), which can be synthesized by the reaction of Cd(II) with rigid linear ligand 4-HIBA containing imidazolyl and carboxylate functional groups [4-HIBA = 4-(1H-imidazol-1-yl)benzoic acid]. Single-crystal X-ray diffraction analyses indicate that complex 1 is a 2D "wave-like" layer structure constructed from trinuclear units and complex 2 is just a mononuclear structure. Surprisingly, both complexes 1 and 2 appear as a 3D supramolecular network via intermolecular hydrogen bonding interactions. What's more, due to their strong UV-visible absorption, 1 and 2 can be employed as co-sensitizers in combination with N719 to enhance dye-sensitized solar cell (DSSC) performance. Both of them could overcome the deficiency of the ruthenium complex N719 absorption in the region of ultraviolet and blue-violet, and the charge collection efficiency is also improved when 1 and 2 are used as co-sensitizers, which are all in favor of enhancing the performance. The DSSC devices using co-sensitizers of 1/N719 and 2/N719 show an overall conversion efficiency of 8.27% and 7.73% with a short circuit current density of 17.48 mA cm(-2) and 17.39 mA cm(-2), and an open circuit voltage of 0.75 V and 0.74 V, respectively. The overall conversion efficiency is 27.23% and 18.92% higher than that of a device solely sensitized by N719 (6.50%). Consequently, the prepared complexes are high efficiency co-sensitizers for enhancing the performance of N719 sensitized solar cells.

  16. 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.

  17. 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.

  18. 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.

  19. Research on test technology of high sensitivity and high frame rate of far ultraviolet spectroscopy

    NASA Astrophysics Data System (ADS)

    Sun, Guang-wei; Sun, Hong-sheng; Wang, Jia-peng; Gao, Shu-min

    2015-10-01

    Importance of ultraviolet calibration is growing fast as ultraviolet payloads are wildly used in national space plan. Calibration device for UV radiation celestial body simulator is established especially for the calibration of instantaneous radiation parameters and high-sensitivity radiation parameters. Parameters such as spectral radiance, spectral irradiance can be calibrated from 200 nm to 400 nm. The uncertainty of spectral radiance is 15% (k=2 and the uncertainty of spectral irradiance is 20% (k=2 .The calibration device is perspective for its application in national defense system.

  20. Rapid qualitative and quantitative analysis of proanthocyanidin oligomers and polymers by UPLC-MS/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proanthocyanidins (PAs) are a structurally complex and bioactive group of tannins. Detailed analysis of PA concentration, composition, and structure typically requires the use of one or more time-consuming analytical methods. For example, the commonly employed thiolysis and phloroglucinolysis method...

  1. 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.

  2. 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.

  3. Carbon nanotube quantum dots as highly sensitive THz spectrometers

    NASA Astrophysics Data System (ADS)

    Rinzan, Mohamed; Jenkins, Greg; Drew, Dennis; Shafranjuk, Serhii; Barbara, Paola

    2012-02-01

    We show that carbon nanotube quantum dots (CNT-Dots) coupled to antennas are extremely sensitive, broad-band, terahertz quantum detectors. Their response is due to photon-assisted single-electron tunneling (PASET)[1], but cannot be fully understood with orthodox PASET models[2]. We consider intra-dot excitations and non-equilibrium cooling to explain the anomalous response. REFERENCES: [1] Y. Kawano, S. Toyokawa, T. Uchida and K. Ishibashi, THz photon assisted tunneling in carbon-nanotube quantum dots, Journal of Applied Physics 103, 034307 (2008). [2] P. K. Tien and J. P. Gordon, Multiphoton Process Observed in the Interaction of Microwave Fields with the Tunneling between Superconductor Films, Phys. Rev. 129, 647 (1963).

  4. 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.

  5. 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

  6. 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.

  7. A high sensitive fiber-optic strain sensor with tunable temperature sensitivity for temperature-compensation measurement

    PubMed Central

    Hu, Jie; Huang, Hui; Bai, Min; Zhan, TingTing; Yang, ZhiBo; Yu, Yan; Qu, Bo

    2017-01-01

    A high sensitive fiber-optic strain sensor, which consists of a cantilever, a tandem rod and a fiber collimator, was proposed. The tandem rod, which transfer the applied strain to the cantilever, was used for tuning the temperature sensitivity from −0.15 to 0.19 dB/°C via changing the length ratio of the rods. Moreover, due to the small beam divergence of the collimator, high strain sensitivity can be realized via incident-angle sensitive detection-mechanism. A strain detection-range of 1.1 × 103 με (with a sensing length of 21.5 mm), a detection limit of 5.7 × 10−3 με, and a maximum operating frequency of 1.18 KHz were demonstrated. This sensor is promising for compensating the thermal-expansion of various target objects. PMID:28205595

  8. 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

  9. Highly sensitive glucose biosensor based on Au-Ni coaxial nanorod array having high aspect ratio.

    PubMed

    Hsu, Che-Wei; Wang, Gou-Jen

    2014-06-15

    An effective glucose biosensor requires a sufficient amount of GOx immobilizing on the electrode surface. An electrode of a 3D nanorod array, having a larger surface-to-volume ratio than a 2D nanostructure, can accommodate more GOx molecules to immobilize onto the surface of the nanorods. In this study, a highly sensitive Au-Ni coaxial nanorod array electrode fabricated through the integration of nano electroforming and immersion gold (IG) method for glucose detection was developed. The average diameter of the as-synthesized Ni nanorods and that of the Au-Ni nanorods were estimated to be 150 and 250 nm, respectively; both had a height of 30 μm. The aspect ratio was 120. Compared to that of a flat Au electrode, the effective sensing area was enhanced by 79.8 folds. Actual glucose detections demonstrated that the proposed Au-Ni coaxial nanorod array electrode could operate in a linear range of 27.5 μM-27.5mM with a detection limit of 5.5μM and a very high sensitivity of 769.6 μA mM(-1)cm(-2). Good selectivity of the proposed sensing device was verified by sequential injections of uric acid (UA) and ascorbic acid (AA). Long-term stability was examined through successive detections over a period of 30 days.

  10. 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.

  11. Highly Sensitive and Robust Damage Detection of Periodic Structures with Piezoelectric Networking

    DTIC Science & Technology

    2008-05-01

    REPORT TYPE Final 3. DATES COVERED (From - To) December 15. 2006 to May 3 1. 2008 4. TITLE AND SUBTITLE Highly Sensitive and Robust Damage...localization characteristics of such periodic structures to enhance damage detection sensitivity and robustness through piezoelectric circuitry...ANSI Sid Z39 18 Adobe Professional 7.0 Highly Sensitive and Robust Damage Detection of Periodic Structures with Piezoelectric Networking GRANT

  12. 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

  13. Highly sensitive homogenous chemiluminescence immunoassay using gold nanoparticles as label

    NASA Astrophysics Data System (ADS)

    Luo, Jing; Cui, Xiang; Liu, Wei; Li, Baoxin

    2014-10-01

    Homogeneous immunoassay is becoming more and more attractive for modern medical diagnosis because it is superior to heterogeneous immunoassay in sample and reagent consumption, analysis time, portability and disposability. Herein, a universal platform for homogeneous immunoassay, using human immunoglobulin G (IgG) as a model analyte, has been developed. This assay relies upon the catalytic activity of gold nanoparticles (AuNPs) on luminol-AgNO3 chemiluminescence (CL) reaction. The immunoreaction of antigen and antibody can induce the aggregation of antibody-functionalized AuNPs, and after aggregation the catalytic activity of AuNPs on luminol-AgNO3 CL reaction is greatly enhanced. Without any separation steps, a CL signal is generated upon addition of a trigger solution, and the CL intensity is directly correlated to the quantity of IgG. The detection limit of IgG was estimated to be as low as 3 pg/mL, and the sensitivity was better than that of the reported AuNPs-based CL immunoassay for IgG.

  14. Achieving tunable sensitivity in composite high-energy density materials

    NASA Astrophysics Data System (ADS)

    Kuklja, Maija M.; Tsyshevsky, Roman V.; Rashkeev, Sergey

    2017-01-01

    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 point 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.

  15. High Sensitive Scintillation Observations At Very Low Frequencies

    NASA Astrophysics Data System (ADS)

    Konovalenko, A. A.; Falkovich, I. S.; Kalinichenko, N. N.; Olyak, M. R.; Lecacheux, A.; Rosolen, C.; Bougeret, J.-L.; Rucker, H. O.; Tokarev, Yu.

    The observation of interplanetary scintillations of compact radio sources is powerful method of solar wind diagnostics. This method is developed mainly at decimeter- meter wavelengths. New possibilities are opened at extremely low frequencies (decameter waves) especially at large elongations. Now this approach is being actively developed using high effective decameter antennas UTR-2, URAN and Nancay Decameter Array. New class of back-end facility like high dynamic range, high resolution digital spectral processors, as well as dynamic spectra determination ideology give us new opportunities for distinguishing of the ionospheric and interplanetary scintillations and for observations of large number of radio sources, whith different angular sizes and elongations, even for the cases of rather weak objects.

  16. 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

  17. 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.

  18. 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...

  19. 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

  20. 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.

  1. 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

  2. Highly sensitive temperature sensor based on an isopropanol-filled photonic crystal fiber long period grating

    NASA Astrophysics Data System (ADS)

    Du, Chao; Wang, Qi; Zhao, Yong; Li, Jin

    2017-03-01

    A high sensitivity measurement method for temperature has been proposed and investigated based on an isopropanol-filled photonic crystal fiber long period grating (PCF-LPG). Due to the high thermo-optic coefficient (TOC) of isopropanol, the sensitivity of the proposed temperature sensor could be effectively improved by filling isopropanol in the air waveguides of PCF. It can be found that the resonant dip will be split in two dips after filling isopropanol and the two dips have different sensitivities to surrounding temperature. Because of PCF-LPG is sensitive to the refractive index (RI) of internal filled liquid, the isopropanol-filled PCF-LPG temperature sensor has a high sensitivities of 1.356 nm/°C in the range of 20-50 °C. The simplicity and the excellent performance of our proposed device make it potential for the applications of high-precision temperature measurement is required.

  3. High Explosive Deonation Threshold Sensitivity Due to Multiple Fragment Impacts

    SciTech Connect

    Georgevich, V; Pincosy, P; Chase, J

    2004-01-07

    Fragments, bullets or projectiles can initiate a detonation in a high explosive (HE). For this to happen certain critical conditions need to be exceeded. For a given explosive, these critical conditions are the projectile velocity, the projectile size and shape, and the projectile material properties. A lot of work has been done in the area of metal shaped charge jets and individual fragments impacting the HE. One major gap in understanding initiation phenomena is the effect of multiple fragment impact. This study shows that multiple fragments can lower the fragment size and the kinetic energy thresholds.

  4. 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

  5. High sensitive and high resolution investigations of the Jovian S-burst emission modulation features

    NASA Astrophysics Data System (ADS)

    Litvinenko, G. V.; Konovalenko, A. A.; Rucker, H. O.; Lecacheux, A.; Vinogradov, V. V.

    2007-08-01

    In spite of the long history of studying, the Jovian S-burst radiation still represents an event which needs to be investigated in detail. Many questions concerning this complex phenomenon are opened. One of the interesting problems is the different modulation features appearing on the dynamic spectra in dependence on the time resolution achieved in the experiment and also on the visualization time scale. It seems that in every concrete case the physical mechanism of the modulation is different. In connection to this the following statistical sets need to be fully collected and analyzed for each modulation effects: 1) observed conditions: dependence or independence on Jupiter - Io - observer position, season time, day-night time, the Solar activity; 2) observed parameters: sign and value of the frequency drift, lane's curvature, modulation depth, distances between the nearest lanes and their variety, scale of the modulation; 3) polarization properties. During the last years the new high sensitive recording facilities, such as the digital spectro-polarimiter (DSP) and waveform receiver (WFR) were created and installed into the largest decameter band antenna array UTR-2 (Kharkov, Ukraine). It can be noted that in the present time this combination (antenna + equipments) gives the best sensitiveness, band of analysis, dynamic range, time and frequency resolutions. The using of mentioned above technique allowed detecting new time-frequency features of the Jovian S-bursts. Several bright new results concerning the modulations were obtained. With the creation of new giant low frequency antenna array (LOFAR) and low wavelength array (LWA) the new possibilities of high level study of the Jovian DAM emission will appear. For instance, the combination of LOFAR and already existing instruments (max base in order of 2000 km) will permit to determine the spatial parameters and localization of an emission source. Future results may prove useful for the general understanding of

  6. A compact high-sensitivity heterodyne interferometer for industrial metrology

    NASA Astrophysics Data System (ADS)

    Schuldt, Thilo; Gohlke, Martin; Weise, Dennis; Peters, Achim; Johann, Ulrich; Braxmaier, Claus

    2008-04-01

    For translation and tilt metrology, we developed a compact fiber-coupled polarizing heterodyne interferometer which is based on a highly symmetric design where both, measurement and reference beam have similar optical pathlengths and the same frequency and polarization. The method of differential wavefront sensing is implemented for tilt measurement. With this setup we reached noise levels below 5 pm/square root of Hz; Hz in translation and below 10 nrad/square root of Hz; in tilt measurement, both for frequencies above 10-2 Hz. While this setup is developed with respect to the requirements of the LISA (Laser Interferometer Space Antenna) space mission, we here present the current status of its adoption to industrial applications. We currently design a very compact and quasi-monolithic setup of the interferometer sensor head based on ultra-low expansion glass material. The resulting compact and robust sensor head can be used for nano-positioning control. We also plan to implement a scan of the measurement beam over the surface under investigation enabling high resolution 3D profilometry and surface property measurements (i. e. roughness, evenness and roundness). The dedicated low-noise (<=1nm/square root of Hz) piezo-electric actuator in the measurement beam of the interferometer will be realized using integrated micro-system technology and can either be implemented in one or two dimensions.

  7. Porous tungsten oxide nanoflakes for highly alcohol sensitive performance.

    PubMed

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

    2012-11-21

    Porous tungsten oxide (WO(3)) nanoflakes have been synthesized by a simple and green approach in an ambient environment. As a precursor solution a polycrystalline hydrated tungstite (H(2)WO(4)·H(2)O) nanoparticles colloid was first prepared by pulsed-laser ablation of a tungsten target in water. The H(2)WO(4)·H(2)O nanoflakes were produced by 72 h aging treatment at room temperature. Finally, porous WO(3) nanoflakes were synthesized by annealing at 800 °C for 4 h. Considering the large surface-to-volume ratio of porous nanoflakes, a porous WO(3) nanoflake gas sensor was fabricated, which exhibits an excellent sensor response performance to alcohol concentrations in the range of 20 to 600 ppm under low working temperature. This high response was attributed to the highly crystalline and porous flake-like morphology, which leads to effective adsorption and desorption, and provides more active sites for the gas molecules' reaction. These findings showed that the porous tungsten oxide nanoflake has great potential in gas-sensing performance.

  8. 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.

  9. High sensitivity, wide coverage, and high-resolution NIR non-cryogenic spectrograph, WINERED

    NASA Astrophysics Data System (ADS)

    Ikeda, Yuji; Kobayashi, Naoto; Kondo, Sohei; Otsubo, Shogo; Hamano, Satoshi; Sameshima, Hiroaki; Yoshikawa, Tomoshiro; Fukue, Kei; Nakanishi, Kenshi; Kawanishi, Takafumi; Nakaoka, Tetsuya; Kinoshita, Masaomi; Kitano, Ayaka; Asano, Akira; Takenaka, Keiichi; Watase, Ayaka; Mito, Hiroyuki; Yasui, Chikako; Minami, Atsushi; Izumu, Natsuko; Yamamoto, Ryo; Mizumoto, Misaki; Arasaki, Takayuki; Arai, Akira; Matsunaga, Noriyuki; Kawakita, Hideyo

    2016-08-01

    Near-infrared (NIR) high-resolution spectroscopy is a fundamental observational method in astronomy. It provides significant information on the kinematics, the magnetic fields, and the chemical abundances, of astronomical objects embedded in or behind the highly extinctive clouds or at the cosmological distances. Scientific requirements have accelerated the development of the technology required for NIR high resolution spectrographs using 10 m telescopes. WINERED is a near-infrared (NIR) high-resolution spectrograph that is currently mounted on the 1.3 m Araki telescope of the Koyama Astronomical Observatory in Kyoto-Sangyo University, Japan, and has been successfully operated for three years. It covers a wide wavelength range from 0.90 to 1.35 μm (the z-, Y-, and J-bands) with a spectral resolution of R = 28,000 (Wide-mode) and R = 80,000 (Hires-Y and Hires-J modes). WINERED has three distinctive features: (i) optics with no cold stop, (ii) wide spectral coverage, and (iii) high sensitivity. The first feature, originating from the Joyce proposal, was first achieved by WINERED, with a short cutoff infrared array, cold baffles, and custom-made thermal blocking filters, and resulted in reducing the time for development, alignment, and maintenance, as well as the total cost. The second feature is realized with the spectral coverage of Δλ/λ 1/6 in a single exposure. This wide coverage is realized by a combination of a decent optical design with a cross-dispersed echelle and a large format array (2k x 2k HAWAII- 2RG). The Third feature, high sensitivity, is achieved via the high-throughput optics (>60 %) and the very low noise of the system. The major factors affecting the high throughput are the echelle grating and the VPH cross-disperser with high diffraction efficiencies of 83 % and 86 %, respectively, and the high QE of HAWAII-2RG (83 % at 1.23 μm). The readout noise of the electronics and the ambient thermal background radiation at longer wavelengths could be

  10. 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.

  11. BCN nanotubes as highly sensitive torsional electromechanical transducers.

    PubMed

    Garel, Jonathan; Zhao, Chong; Popovitz-Biro, Ronit; Golberg, Dmitri; Wang, Wenlong; Joselevich, Ernesto

    2014-11-12

    Owing to their mechanically tunable electronic properties, carbon nanotubes (CNTs) have been widely studied as potential components for nanoelectromechanical systems (NEMS); however, the mechanical properties of multiwall CNTs are often limited by the weak shear interactions between the graphitic layers. Boron nitride nanotubes (BNNTs) exhibit a strong interlayer mechanical coupling, but their high electrical resistance limits their use as electromechanical transducers. Can the outstanding mechanical properties of BNNTs be combined with the electromechanical properties of CNTs in one hybrid structure? Here, we report the first experimental study of boron carbonitride nanotube (BCNNT) mechanics and electromechanics. We found that the hybrid BCNNTs are up to five times torsionally stiffer and stronger than CNTs, thereby retaining to a large extent the ultrahigh torsional stiffness of BNNTs. At the same time, we show that the electrical response of BCNNTs to torsion is 1 to 2 orders of magnitude higher than that of CNTs. These results demonstrate that BCNNTs could be especially attractive building blocks for NEMS.

  12. The development of a high sensitivity neutron displacement damage sensor

    DOE PAGES

    Tonigan, Andrew M.; Parma, Edward J.; Martin, William J.

    2016-11-23

    Here, the capability to characterize the neutron energy spectrum and fluence received by a test object is crucial to under-standing the damage effects observed in electronic components. For nuclear research reactors and high energy density physics fa-cilities this can pose exceptional challenges, especially with low level neutron fluences. An ASTM test method for characterizing neutron environments utilizes the 2N2222A transistor as a 1-MeV equivalent neutron fluence sensor and is applicable for environ-ments with 1 x 1012 - 1 x 1014 1-MeV(Si)-Eqv.-n/cm2. In this work we seek to extend the range of this test method to lower fluence environments utilizing themore » 2N1486 transistor. Here, the 2N1486 is shown to be an effective neutron displacement damage sensor as low as 1 x 1010 1-MeV(Si)-Eqv.-n/cm2.« less

  13. Determination of nine environmental phenols in urine by ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Chen, Minjian; Zhu, Pengfei; Xu, Bin; Zhao, Rencheng; Qiao, Shanlei; Chen, Xiaojiao; Tang, Rong; Wu, Di; Song, Ling; Wang, Shoulin; Xia, Yankai; Wang, Xinru

    2012-01-01

    A method was developed to determine nine environmental phenols, including bisphenol A, 2,3,4-trichlorophenol, 2,4,5-trichlorophenol, pentachlorophenol, triclosan (2,4,4'-trichloro-2'-hydroxyphenylether), 4-tert-octylphenol, 4-n-octylphenol, 4-n-nolyphenol and benzophenone-3 (2-hydroxy-4-methoxybenzophenone) in human urine using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). The analytes were extracted and preconcentrated with solid-phase extraction, and then quantified with UPLC-electrospray ionization (negative ion mode)-MS-MS using multiple reaction monitoring mode. Limits of detection of the nine phenols ranged from 0.02 to 0.90 ng/mL. This method was further validated by the determination of phenols in 325 human urine samples that generated data regarding the exposure of various phenols to Chinese adults without occupational exposure to phenols.

  14. The development of a high sensitivity neutron displacement damage sensor

    SciTech Connect

    Tonigan, Andrew M.; Parma, Edward J.; Martin, William J.

    2016-11-23

    Here, the capability to characterize the neutron energy spectrum and fluence received by a test object is crucial to under-standing the damage effects observed in electronic components. For nuclear research reactors and high energy density physics fa-cilities this can pose exceptional challenges, especially with low level neutron fluences. An ASTM test method for characterizing neutron environments utilizes the 2N2222A transistor as a 1-MeV equivalent neutron fluence sensor and is applicable for environ-ments with 1 x 1012 - 1 x 1014 1-MeV(Si)-Eqv.-n/cm2. In this work we seek to extend the range of this test method to lower fluence environments utilizing the 2N1486 transistor. Here, the 2N1486 is shown to be an effective neutron displacement damage sensor as low as 1 x 1010 1-MeV(Si)-Eqv.-n/cm2.

  15. 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.

  16. 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.

  17. 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.

  18. Enhanced laboratory sensitivity to variation of the fine-structure constant using highly charged ions.

    PubMed

    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 α. 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 α sensitivities seen in atomic systems.

  19. Sensory Processing Sensitivity: Factors of the Highly Sensitive Person Scale and Their relationships to Personality and Subjective Health Complaints.

    PubMed

    Listou Grimen, Hanne; Diseth, Åge

    2016-12-01

    The aim of the present study was to examine the factor structure of a Norwegian version of the Highly Sensitive Person Scale (HSPS) and to investigate how sensory processing sensitivity (SPS) is related to personality traits of neuroticism, extraversion, and openness and to subjective health complaints (SHC) in a sample of 167 undergraduate psychology students. The results showed that the variance in a shortened version of the HSPS was best described by three separate factors: ease of excitation (EOE), aesthetic sensitivity (AES), and low sensory threshold (LST). Furthermore, the result showed than an overall SPS factor (EOE, LST, and AES combined) was predicted positively by neuroticism and openness and negatively by extraversion. With respect to SHC, the results showed that EOE and LST were positively associated with psychological health complaints. However, the personality trait of neuroticism contributed more than the SPS factors as predictor of SHC. In conclusion, the present study supported a shortened version of the HSPS and its relation to personality factors and SHC.

  20. Highly sensitive surface plasmon resonance chemical sensor based on Goos-Hanchen effects

    NASA Astrophysics Data System (ADS)

    Yin, Xiaobo; Hesselink, Lambertus

    2006-08-01

    The resonance enhanced Goos-Hanchen shifts at attenuated total internal reflection enables the possibility for highly sensitive surface plasmon resonance sensor. The observed giant displacements result from the singular phase retardation at the resonance where the phase is continuous but changes dramatically. The phenomenon is proposed for chemical sensing and the superior sensitivity is demonstrated.

  1. 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.

  2. Improvement in the definition of anti-HLA antibody profile in highly sensitized patients.

    PubMed

    Irure, Juan; Asensio, Esther; Rodrigo, Emilio; Romón, Íñigo; Gómez, Javier; Arias, Manuel; López-Hoyos, Marcos; San Segundo, David

    2017-01-01

    The definition of anti-HLA antibody profile in highly sensitized patients on a waiting list is crucial when virtual crossmatch is used in organ allocation systems, but also when used to identify the true deleterious anti-HLA antibodies. Here we propose different levels of risk based on the results of anti-HLA antibody testing in neat serum (N) and after sera dilution (DIL) and C1q test in 18 highly sensitized patients. This group was heterogeneous in terms of anti-HLA antibody titers and their ability to fix complement. After dilution, 15 out of 18 patients (83.3%) showed a reduction of positive bead counts whereas 4 patients showed a prozone effect and complement fixation was demonstrated. The high dilution of sera and ascertaining the complement fixation allow the accurate definition of risk anti-HLA antibody profiles in highly sensitized patients, as demonstrated in 5 of the sensitized patients who were transplanted.

  3. Improvement in the definition of anti-HLA antibody profile in highly sensitized patients

    PubMed Central

    Irure, Juan; Asensio, Esther; Rodrigo, Emilio; Romón, Íñigo; Gómez, Javier; Arias, Manuel

    2017-01-01

    The definition of anti-HLA antibody profile in highly sensitized patients on a waiting list is crucial when virtual crossmatch is used in organ allocation systems, but also when used to identify the true deleterious anti-HLA antibodies. Here we propose different levels of risk based on the results of anti-HLA antibody testing in neat serum (N) and after sera dilution (DIL) and C1q test in 18 highly sensitized patients. This group was heterogeneous in terms of anti-HLA antibody titers and their ability to fix complement. After dilution, 15 out of 18 patients (83.3%) showed a reduction of positive bead counts whereas 4 patients showed a prozone effect and complement fixation was demonstrated. The high dilution of sera and ascertaining the complement fixation allow the accurate definition of risk anti-HLA antibody profiles in highly sensitized patients, as demonstrated in 5 of the sensitized patients who were transplanted. PMID:28158255

  4. Cavity-enhanced room-temperature high sensitivity optical Faraday magnetometry

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Lei, Yaohua; Fan, Shuangli; Zhang, Qiaolin; Guo, Hong

    2017-01-01

    We propose a cavity QED system with two-photon Doppler-free configuration for weak magnetic field detection with high sensitivity at room temperature based on cavity electromagnetically induced transparency. Owing to the destructive interference induced by the control and driving fields, two transparency channels are opened. The Faraday rotation within two transparency channels can be used to detect weak magnetic field with high sensitivity at room temperature. The sensitivity with single photon and multiphoton probe inputs is analyzed. With single photon measurement, our numerical calculations demonstrate that the sensitivity with 3.8nT/√{Hz} and 6.4nT/√{Hz} could be achieved. When we measure the magnetic field with multiphoton input, the sensitivity can be improved to 7.7fT/√{Hz} and 25.6fT/√{Hz} under the realistic experimental conditions.

  5. 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.

  6. Periodically Porous Top Electrodes on Vertical Nanowire Arrays for Highly Sensitive Gas Detection

    DTIC Science & Technology

    2011-08-01

    highly sensitive detection to both nitrogen dioxide (NO2) and ammonia (NH3) in humidified air. NO2 detection down to 10 parts per billion (ppb) is... humidified air. NO2 detection down to 10 parts per billion (ppb) is demonstrated and an order-of-magnitude improvement in sensor response time is shown in...controllable size and distribution. Fast and highly sensitive detection of ammonia and nitrogen dioxide in humidified air using the PTE nanowire array sensor

  7. Making sense of high sensitivity troponin assays and their role in clinical care.

    PubMed

    Daniels, Lori B

    2014-04-01

    Cardiac troponin assays have an established and undisputed role in the diagnosis and risk stratification of patients with acute myocardial infarction. As troponin assays gets more sensitive and more precise, the number of potential uses has rapidly expanded, but the use of this test has also become more complicated and controversial. Highly sensitive troponin assays can now detect troponin levels in most individuals, but accurate interpretation of these levels requires a clear understanding of the assay in the context of the clinical scenario. This paper provides a practical and up-to-date overview of the uses of highly sensitive troponin assays for diagnosis, prognosis, and risk stratification in clinical practice.

  8. High-sensitivity strain sensor based on inflated long period fiber grating.

    PubMed

    Zhong, Xiaoyong; Wang, Yiping; Qu, Junle; Liao, Changrui; Liu, Shen; Tang, Jian; Wang, Qiao; Zhao, Jing; Yang, Kaiming; Li, Zhengyong

    2014-09-15

    We demonstrated a high-sensitivity strain sensor based on an inflated long period fiber grating (I-LPFG). The I-LPFG was inscribed, for the first time to the best of our knowledge, by use of the pressure-assisted CO(2) laser beam scanning technique to inflate periodically air holes of a photonic crystal fiber. Such periodic inflations enhanced the sensitivity of the LPFG-based strain sensor to -5.62 pm/με. After high temperature annealing, the I-LPFG achieved a good repeatability and stability of temperature response with a sensitivity of 11.92 pm/°C.

  9. Highly sensitive biochemical sensor utilizing Bragg grating in submicron Si/SiO2 waveguides

    NASA Astrophysics Data System (ADS)

    Tripathi, Saurabh Mani; Kumar, Arun; Meunier, Jean-Pierre; Marin, Emmanuel

    2009-05-01

    We present a novel highly sensitive biochemical sensor based on a Bragg grating written in the cladding region of a submicron planar Si/SiO2 waveguide. Owing to the high refractive index contrast at the Si/SiO2 boundary the TM modal power is relatively high in low refractive index sensing region, leading to higher sensitivity in this configuration [1]. Waveguide parameters have been optimized to obtain maximum modal power in the sensing region (PSe) and an optimum core width corresponding to maximum sensitivity is found to exist while operating in TM mode configuration, as has been shown in Fig. 1. It has been found that operating in TM mode configuration at optimum core width the structure exhibits extremely high sensitivity, ~ 5×10-6 RIU - 1.35×10-6 RIU for the ambient refractive indices between 1.33 - 1.63. Such high sensitivities are typically attainable for Surface Plasmon Polariton (SPP) based biosensors and is much higher than any non SPP based sensors. Being free from any metallic layer or bulky prism the structure is easy to realize. Owing to its simple structure and small dimensions the proposed sensor can be integrated with planar lightwave circuits and could be used in handy lab-on-a-chip devices. The device may find application in highly sensitive biological/chemical sensing areas in civil and defense sectors where analyzing the samples at the point of need is required rather than sending it to some centralized laboratory.

  10. Enhance the optical absorptivity of nanocrystalline TiO2 film with high molar extinction coefficient ruthenium sensitizers for high performance dye-sensitized solar cells.

    PubMed

    Gao, Feifei; Wang, Yuan; Shi, Dong; Zhang, Jing; Wang, Mingkui; Jing, Xiaoyan; Humphry-Baker, Robin; Wang, Peng; Zakeeruddin, Shaik M; Grätzel, Michael

    2008-08-13

    We report two new heteroleptic polypyridyl ruthenium complexes, coded C101 and C102, with high molar extinction coefficients by extending the pi-conjugation of spectator ligands, with a motivation to enhance the optical absorptivity of mesoporous titania film and charge collection yield in a dye-sensitized solar cell. On the basis of this C101 sensitizer, several DSC benchmarks measured under the air mass 1.5 global sunlight have been reached. Along with an acetonitrile-based electrolyte, the C101 sensitizer has already achieved a strikingly high efficiency of 11.0-11.3%, even under a preliminary testing. More importantly, based on a low volatility 3-methoxypropionitrile electrolyte and a solvent-free ionic liquid electrolyte, cells have corresponding >9.0% and approximately 7.4% efficiencies retained over 95% of their initial performances after 1000 h full sunlight soaking at 60 degrees C. With the aid of electrical impedance measurements, we further disclose that, compared to the cell with an acetonitrile-based electrolyte, a dye-sensitized solar cell with an ionic liquid electrolyte shows a feature of much shorter effective electron diffusion lengths due to the lower electron diffusion coefficients and shorter electron lifetimes in the mesoporous titania film, explaining the photocurrent difference between these two type devices. This highlights the next necessary efforts to further improve the efficiency of cells with ionic liquid electrolytes, facilitating the large-scale production and application of flexible thin film mesoscopic solar cells.

  11. Comparison of different calibration approaches for chloramphenicol quantification in chicken muscle by ultra-high pressure liquid chromatography tandem mass spectrometry.

    PubMed

    Pan, Xiao-Dong; Jiang, Wei; Wu, Ping-Gu

    2015-01-07

    Matrix-dependent signal suppression often occurs in quantitative analysis by ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS). In this study, we investigated three calibration methods for compensation of signal suppression on chloramphenicol (CAP) quantification in chicken muscle. The data showed that the spiking recoveries by solvent standard calibration with a stable isotope labelled internal standard (SIL-IS) and matrix-matched standard calibration with a SIL-IS were significantly higher than by external matrix-matched standard calibration (P < 0.05). When the SIL-IS was used, standards prepared in the mobile phase solvent showed no significant difference as those prepared in the matrix (P > 0.05). The limit of detection (LOD) for external matrix matched standard calibration was 0.1 μg kg(-1), and that for SIL-IS calibration (including matrix matched and solvent dissolved standard) was 0.03 μg kg(-1).

  12. A multiresidue approach for the simultaneous quantification of antibiotics in macroalgae by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Leston, Sara; Freitas, Andreia; Rosa, João; Barbosa, Jorge; Lemos, Marco F L; Pardal, Miguel Ângelo; Ramos, Fernando

    2016-10-15

    Together with fish, algae reared in aquaculture systems have gained importance in the last years, for many purposes. Besides their use as biofilters of effluents, macroalgae's rich nutritional profiles have increased their inclusion in human diets but also in animal feeds as sources of fatty acids, especially important for the fish industry. Nonetheless, algae are continuously exposed to environmental contaminants including antibiotics and possess the ability for bioaccumulation of such compounds. Therefore, the present paper describes the development and validation of an ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of antibiotics in the green macroalgae Ulva lactuca. This multi-residue method enables the determination of 38 compounds distributed between seven classes and was fully validated according to EU Decision 2002/657/EC.

  13. 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.

  14. Fano resonance-based highly sensitive, compact temperature sensor on thin film lithium niobate.

    PubMed

    Qiu, Wentao; Ndao, Abdoulaye; Vila, Venancio Calero; Salut, Roland; Courjal, Nadège; Baida, Fadi Issam; Bernal, Maria-Pilar

    2016-03-15

    In this Letter, we report a Fano resonance-based highly sensitive and compact temperature sensor fabricated on thin film lithium niobate (TFLN) Suzuki phase lattice (SPL) photonic crystal. The experimental sensitivity is estimated to be 0.77 nm/°C with a photonic crystal size of only 25  μm × 24  μm. This sensitivity is 38 times larger than the intrinsic one of lithium niobate which is 0.02 nm/°C. The demonstrated sharp and high extinction ratio characteristics of the Fano lineshape resonance could be an excellent candidate in developing a high sensitivity temperature sensor, electric field sensor, etc.

  15. Highly sensitive electronic whiskers based on patterned carbon nanotube and silver nanoparticle composite films.

    PubMed

    Takei, Kuniharu; Yu, Zhibin; Zheng, Maxwell; Ota, Hiroki; Takahashi, Toshitake; Javey, Ali

    2014-02-04

    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.

  16. Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis.

    PubMed

    Masillo, A; Valmaggia, L R; Saba, R; Brandizzi, M; Lindau, J F; Solfanelli, A; Curto, M; Narilli, F; Telesforo, L; Kotzalidis, G D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

    2016-01-01

    A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals.

  17. 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.

  18. Proposed helmet PET geometries with add-on detectors for high sensitivity brain imaging.

    PubMed

    Tashima, Hideaki; Yamaya, Taiga

    2016-10-07

    For dedicated brain PET, we can significantly improve sensitivity for the cerebrum region by arranging detectors in a compact hemisphere. The geometrical sensitivity for the top region of the hemisphere is increased compared with conventional cylindrical PET consisting of the same number of detectors. However, the geometrical sensitivity at the center region of the hemisphere is still low because the bottom edge of the field-of-view is open, the same as for the cylindrical PET. In this paper, we proposed a helmet PET with add-on detectors for high sensitivity brain PET imaging for both center and top regions. The key point is the add-on detectors covering some portion of the spherical surface in addition to the hemisphere. As the location of the add-on detectors, we proposed three choices: a chin detector, ear detectors, and a neck detector. For example, the geometrical sensitivity for the region-of-interest at the center was increased by 200% by adding the chin detector which increased the size by 12% of the size of the hemisphere detector. The other add-on detectors gave almost the same increased sensitivity effect as the chin detector did. Compared with standard whole-body-cylindrical PET, the proposed geometries can achieve 2.6 times higher sensitivity for brain region even with less than 1/4 detectors. In addition, we conducted imaging simulations for geometries with a diameter of 250 mm and with high resolution depth-of-interaction detectors. The simulation results showed that the proposed geometries increased image quality, and all of the add-on detectors were equivalently effective. In conclusion, the proposed geometries have high potential for widespread applications in high-sensitivity, high-resolution, and low-cost brain PET imaging.

  19. Proposed helmet PET geometries with add-on detectors for high sensitivity brain imaging

    NASA Astrophysics Data System (ADS)

    Tashima, Hideaki; Yamaya, Taiga

    2016-10-01

    For dedicated brain PET, we can significantly improve sensitivity for the cerebrum region by arranging detectors in a compact hemisphere. The geometrical sensitivity for the top region of the hemisphere is increased compared with conventional cylindrical PET consisting of the same number of detectors. However, the geometrical sensitivity at the center region of the hemisphere is still low because the bottom edge of the field-of-view is open, the same as for the cylindrical PET. In this paper, we proposed a helmet PET with add-on detectors for high sensitivity brain PET imaging for both center and top regions. The key point is the add-on detectors covering some portion of the spherical surface in addition to the hemisphere. As the location of the add-on detectors, we proposed three choices: a chin detector, ear detectors, and a neck detector. For example, the geometrical sensitivity for the region-of-interest at the center was increased by 200% by adding the chin detector which increased the size by 12% of the size of the hemisphere detector. The other add-on detectors gave almost the same increased sensitivity effect as the chin detector did. Compared with standard whole-body-cylindrical PET, the proposed geometries can achieve 2.6 times higher sensitivity for brain region even with less than 1/4 detectors. In addition, we conducted imaging simulations for geometries with a diameter of 250 mm and with high resolution depth-of-interaction detectors. The simulation results showed that the proposed geometries increased image quality, and all of the add-on detectors were equivalently effective. In conclusion, the proposed geometries have high potential for widespread applications in high-sensitivity, high-resolution, and low-cost brain PET imaging.

  20. 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.

  1. Fully printed, highly sensitive multifunctional artificial electronic whisker arrays integrated with strain and temperature sensors.

    PubMed

    Harada, Shingo; Honda, Wataru; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu

    2014-04-22

    Mammalian-mimicking functional electrical devices have tremendous potential in robotics, wearable and health monitoring systems, and human interfaces. The keys to achieve these devices are (1) highly sensitive sensors, (2) economically fabricated macroscale devices on flexible substrates, and (3) multifunctions beyond mammalian functions. Although highly sensitive artificial electronic devices have been reported, none have been fabricated using cost-effective macroscale printing methods and demonstrate multifunctionalities of artificial electronics. Herein we report fully printed high-sensitivity multifunctional artificial electronic whiskers (e-whisker) integrated with strain and temperature sensors using printable nanocomposite inks. Importantly, changing the composition ratio tunes the sensitivity of strain. Additionally, the printed temperature sensor array can be incorporated with the strain sensor array beyond mammalian whisker functionalities. The sensitivity for the strain sensor is impressively high (∼59%/Pa), which is the best sensitivity reported to date (>7× improvement). As the proof-of-concept for a truly printable multifunctional artificial e-whisker array, two- and three-dimensional space and temperature distribution mapping are demonstrated. This fully printable flexible sensor array should be applicable to a wide range of low-cost macroscale electrical applications.

  2. High maltose sensitivity of sweet taste receptors in the Japanese macaque (Macaca fuscata)

    PubMed Central

    Nishi, Emiko; Tsutsui, Kei; Imai, Hiroo

    2016-01-01

    Taste sensitivity differs among animal species depending on feeding habitat. To humans, sucrose is one of the sweetest natural sugars, and this trait is expected to be similar in other primates. However, previous behavioral tests have shown that some primate species have equal preferences for maltose and sucrose. Because sweet tastes are recognized when compounds bind to the sweet taste receptor Tas1R2/Tas1R3, we evaluated the responses of human and Japanese macaque Tas1R2/Tas1R3 to various natural sugars using a heterologous expression system. Human Tas1R2/Tas1R3 showed high sensitivity to sucrose, as expected; however, Japanese macaque Tas1R2/Tas1R3 showed equally high sensitivity to maltose and sucrose. Furthermore, Japanese macaques showed equally high sensitivity to sucrose and maltose in a two-bottle behavioral experiment. These results indicate that Japanese macaques have high sensitivity to maltose, and this sensitivity is directly related to Tas1R2/Tas1R3 function. This is the first molecular biological evidence that for some primate species, sucrose is not the most preferable natural sugar, as it is for humans. PMID:27982108

  3. Numerical study on an application of subwavelength dielectric gratings for high-sensitivity plasmonic detection.

    PubMed

    Jung, Woo Kyung; Kim, Nak-Hyeon; Byun, Kyung Min

    2012-07-10

    Although subwavelength dielectric gratings can be employed to achieve a high sensitivity of the surface plasmon resonance (SPR) biosensor, the plasmonic interpretation verifying the resulting sensitivity improvement remains unclear. The aim of this study is to elucidate the effects of the grating's geometric parameters on the amplification of SPR responses and to understand the physical mechanisms associated with the enhancement. Our numerical results show that the proposed SPR substrate with a dielectric grating can provide a better sensitivity due to the combined effects of surface reaction area and field distribution at the binding region. An influence of adhesion layer on the sensor performance is also discussed. The obtained results will be promising in high-sensitivity plasmonic biosensing applications.

  4. Highly sensitive detection of dipicolinic acid with a water-dispersible terbium-metal organic framework.

    PubMed

    Bhardwaj, Neha; Bhardwaj, Sanjeev; Mehta, Jyotsana; Kim, Ki-Hyun; Deep, Akash

    2016-12-15

    The sensitive detection of dipicolinic acid (DPA) is strongly associated with the sensing of bacterial organisms in food and many types of environmental samples. To date, the demand for a sensitive detection method for bacterial toxicity has increased remarkably. Herein, we investigated the DPA detection potential of a water-dispersible terbium-metal organic framework (Tb-MOF) based on the fluorescence quenching mechanism. The Tb-MOF showed a highly sensitive ability to detect DPA at a limit of detection of 0.04nM (linear range of detection: 1nM to 5µM) and also offered enhanced selectivity from other commonly associated organic molecules. The present study provides a basis for the application of Tb-MOF for direct, convenient, highly sensitive, and specific detection of DPA in the actual samples.

  5. Green laser excited surface plasmon resonance biosensor utilizing highly sensitive phase interrogation detection

    NASA Astrophysics Data System (ADS)

    Chen, How-Foo; Hsu, Wei-Chen; Wang, Ya-Jung; Yen, Ta-Jen

    2010-04-01

    Surface plasmon resonance (SPR) biosensors have been widely used for dynamical analysis of molecular affinity, bacterium screening, and drug discovery due to its advantages of label-free detection, dynamic interaction analysis, small sample volume, and ultra sensitivity (feasibility of single molecular detection). Recently, SPR biosensing for cell imaging known as SPR microscopy (SPRM) has attracted great attention due to the characteristics of SPR biosensors. However, it is well known that the trends of sensitivity and spatial resolution are opposite to each other: Surface plasmon waves (SPWs) with shorter wavelength which provides higher spatial resolution has less sensitivity. It is known that the spatial resolution of SPRM is limited by the propagation length of surface plasmon wave (SPW) along the metaldielectric interface. SPW excited by 632.8 nm light has the propagation length of 3 um. This length becomes longer when a longer wavelength is selected. While most of SPR biosensors are built with 632.8 nm or longer wavelength for high sensitivity, using 532nm light to excite SPWs is desired for submicron resolution since the propagation length is around 150 nm. Different from current phase interrogation methods, the proposed phase interrogation method is highly sensitive and suitable for CCD imaging. Although it is generally believed that SPWs with wavelength 532nm has poor sensitivity, the experimental result showed that the setup can reach the sensitivity lower than 2×10-6 RIU when sucrose is used as the test sample.

  6. Biofunctionalized magnetic nanoparticles for high-sensitivity immunomagnetic detection of human C-reactive protein

    NASA Astrophysics Data System (ADS)

    Horng, H. E.; Yang, S. Y.; Hong, Chin-Yih; Liu, C. M.; Tsai, P. S.; Yang, H. C.; Wu, C. C.

    2006-06-01

    In this work, we developed immunomagnetic detection techniques for detecting human C-reactive protein (CRP). To enhance the technique's sensitivity to human CRP, biofunctionalized magnetic nanoparticles were used as markers, and a superconductive quantum interference device gradiometer system was adapted to measure the saturated magnetization of magnetically labeled CRP-anti-CRP immune complexes. Sensitivity for human CRP was found to be as high as 1ng in 0.1ml, i.e., 10ng/ml in concentration. This sensitivity is much higher than that of conventional enzyme linked immunosorbent assay by one order of magnitude.

  7. Numerical analysis of a side-hole birefringent photonic crystal fiber with high-pressure sensitivity

    NASA Astrophysics Data System (ADS)

    Li, Duanming; Zhang, Wei; Zhou, Guiyao

    2016-09-01

    A birefringent structured side-holes photonic crystal fiber (PCF) with high sensitivity is designed for pressure sensing. Simulation results show that the birefringence and relevant sensitivity are strongly influenced by the air-holes' sizes and the distance between the fiber core and side-hole. The modal birefringence and the polarimetric pressure sensitivity can be up to 3.943×10-3 and -3.67×10-5 MPa-1 at 1.55 μm, respectively. The proposed side-holes PCF possesses promising applications for pressure sensing.

  8. High sensitivity to variation in the proton-to-electron mass ratio in O2+

    NASA Astrophysics Data System (ADS)

    Hanneke, D.; Carollo, R. A.; Lane, D. A.

    2016-11-01

    Molecular vibrational transitions are prime candidates for model-independent searches for variation of the proton-to-electron mass ratio. Searches for present-day variation achieve the highest sensitivity with deep molecular potentials. We identify several high-sensitivity transitions in the deeply bound O2+ molecular ion. These transitions are electric-dipole forbidden and have narrow linewidths. The most sensitive transitions take advantage of an accidental degeneracy between vibrational states in different electronic potentials. We suggest experimentally feasible routes to a measurement with uncertainty below current limits on present-day variation in mp/me .

  9. Highly sensitive refractive index sensor based on cascaded microfiber knots with Vernier effect.

    PubMed

    Xu, Zhilin; Sun, Qizhen; Li, Borui; Luo, Yiyang; Lu, Wengao; Liu, Deming; Shum, Perry Ping; Zhang, Lin

    2015-03-09

    We propose and experimentally demonstrate a refractive index (RI) sensor based on cascaded microfiber knot resonators (CMKRs) with Vernier effect. Deriving from high proportional evanescent field of microfiber and spectrum magnification function of Vernier effect, the RI sensor shows high sensitivity as well as high detection resolution. By using the method named "Drawing-Knotting-Assembling (DKA)", a compact CMKRs is fabricated for experimental demonstration. With the assistance of Lorentz fitting algorithm on the transmission spectrum, sensitivity of 6523nm/RIU and detection resolution up to 1.533 × 10(-7)RIU are obtained in the experiment which show good agreement with the numerical simulation. The proposed all-fiber RI sensor with high sensitivity, compact size and low cost can be widely used for chemical and biological detection, as well as the electronic/magnetic field measurement.

  10. Highly sensitive refractive index sensor based on two cascaded microfiber knots with Vernier effect

    NASA Astrophysics Data System (ADS)

    Xu, Zhilin; Sun, Qizhen; Jia, Weihua; Shum, Perry Ping; Liu, Deming

    2014-05-01

    A highly sensitive refractive index (RI) sensor based on two cascaded microfiber knots with vernier effect is proposed and demonstrated by theoretical arithmetic. Deriving from high proportional evanescent field of microfiber and sharp spectrum fringes induced by vernier effect, a slight change of ambient RI will cause large variation of effective RI and significant wavelength shift of resonant peaks, indicating high sensitivity and resolution of the proposed compound resonator. Numerical analysis demonstrates a high sensitivity of 10000nm/RIU and a resolution of 5.57×10-5 RIU at the ambient RI around 1.33 for the fiber diameter of 1μm and cavity radii of R1 = 500μm, R2 = 547.62μm

  11. Highly asymmetrical porphyrins with enhanced push-pull character for dye-sensitized solar cells.

    PubMed

    Kurotobi, Kei; Toude, Yuuki; Kawamoto, Kyosuke; Fujimori, Yamato; Ito, Seigo; Chabera, Pavel; Sundström, Villy; Imahori, Hiroshi

    2013-12-09

    A porphyrin π-system has been modulated by enhancing the push-pull character with highly asymmetrical substitution for dye-sensitized solar cells for the first time. Namely, both two diarylamino moieties as a strong electron-donating group and one carboxyphenylethynyl moiety as a strong electron-withdrawing, anchoring group were introduced into the meso-positions of the porphyrin core in a lower symmetrical manner. As a result of the improved light-harvesting property as well as high electron distribution in the anchoring group of LUMO, a push-pull-enhanced, porphyrin-sensitized solar cell exhibited more than 10% power conversion efficiency, which exceeded that of a representative highly efficient porphyrin (i.e., YD2)-sensitized solar cell under optimized conditions. The rational molecular design concept based on highly asymmetric, push-pull substitution will open the possibilities of further improving cell performance in organic solar cells.

  12. 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.

  13. The Sensitivity of Adolescent School-Based Hearing Screens Is Significantly Improved by Adding High Frequencies

    ERIC Educational Resources Information Center

    Sekhar, Deepa L.; Zalewski, Thomas R.; Beiler, Jessica S.; Czarnecki, Beth; Barr, Ashley L.; King, Tonya S.; Paul, Ian M.

    2016-01-01

    High frequency hearing loss (HFHL), often related to hazardous noise, affects one in six U.S. adolescents. Yet, only 20 states include school-based hearing screens for adolescents. Only six states test multiple high frequencies. Study objectives were to (1) compare the sensitivity of state school-based hearing screens for adolescents to gold…

  14. 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.

  15. 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.

  16. 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.

  17. Highly sensitive ion-sensitive field-effect transistor sensor using fully transparent amorphous In–Ga–Zn–O thin-film transistors

    NASA Astrophysics Data System (ADS)

    Ahn, Min-Ju; Lim, Cheol-Min; Cho, Won-Ju

    2017-03-01

    In this study, a highly sensitive ion-sensitive field-effect transistor (ISFET) sensor was developed using fully transparent amorphous In–Ga–Zn–O thin-film transistors fabricated on a glass substrate. To overcome the issues associated with conventional ISFETs, such as low sensitivity and poor reliability, a dual-gate (DG) operating mode was employed, which is able to significantly amplify the sensitivity through capacitive coupling between the front and back gate dielectrics. As a result, when compared to the sensitivity in the single-gate mode, the DG mode exhibited a high sensitivity of 269.3 mV/pH, which is beyond the Nernst response limit.

  18. Highly adaptable and sensitive protease assay based on fluorescence resonance energy transfer.

    PubMed

    Zauner, Thomas; Berger-Hoffmann, Renate; Müller, Katrin; Hoffmann, Ralf; Zuchner, Thole

    2011-10-01

    Proteases are widely used in analytical sciences and play a central role in several widespread diseases. Thus, there is an immense need for highly adaptable and sensitive assays for the detection and monitoring of various proteolytic enzymes. We established a simple protease fluorescence resonance energy transfer (pro-FRET) assay for the determination of protease activities, which could in principle be adapted for the detection of all proteases. As proof of principle, we demonstrated the potential of our method using trypsin and enteropeptidase in complex biological mixtures. Briefly, the assay is based on the cleavage of a FRET peptide substrate, which results in a dramatic increase of the donor fluorescence. The assay was highly sensitive and fast for both proteases. The detection limits for trypsin and enteropeptidase in Escherichia coli lysate were 100 and 10 amol, respectively. The improved sensitivity for enteropeptidase was due to the application of an enzyme cascade, which leads to signal amplification. The pro-FRET assay is highly specific as even high concentrations of other proteases did not result in significant background signals. In conclusion, this sensitive and simple assay can be performed in complex biological mixtures and can be easily adapted to act as a versatile tool for the sensitive detection of proteases.

  19. The Design and Optimization of a Highly Sensitive and Overload-Resistant Piezoresistive Pressure Sensor.

    PubMed

    Meng, Xiawei; Zhao, Yulong

    2016-03-09

    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.

  20. 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.

  1. The Sensitivity of Adolescent School-Based Hearing Screens Is Significantly Improved by Adding High Frequencies.

    PubMed

    Sekhar, Deepa L; Zalewski, Thomas R; Beiler, Jessica S; Czarnecki, Beth; Barr, Ashley L; King, Tonya S; Paul, Ian M

    2016-12-01

    High frequency hearing loss (HFHL), often related to hazardous noise, affects one in six U.S. adolescents. Yet, only 20 states include school-based hearing screens for adolescents. Only six states test multiple high frequencies. Study objectives were to (1) compare the sensitivity of state school-based hearing screens for adolescents to gold standard sound-treated booth testing and (2) consider the effect of adding multiple high frequencies and two-step screening on sensitivity/specificity. Of 134 eleventh-grade participants (2013-2014), 43 of the 134 (32%) did not pass sound-treated booth testing, and 27 of the 43 (63%) had HFHL. Sensitivity/specificity of the most common protocol (1,000, 2,000, 4,000 Hz at 20 dB HL) for these hearing losses was 25.6% (95% confidence interval [CI] = [13.5, 41.2]) and 85.7% (95% CI [76.8, 92.2]), respectively. A protocol including 500, 1,000, 2,000, 4,000, 6,000 Hz at 20 dB HL significantly improved sensitivity to 76.7% (95% CI [61.4, 88.2]), p < .001. Two-step screening maintained specificity (84.6%, 95% CI [75.5, 91.3]). Adolescent school-based hearing screen sensitivity improves with high frequencies.

  2. Highly sensitive glucose sensors based on enzyme-modified whole-graphene solution-gated transistors.

    PubMed

    Zhang, Meng; Liao, Caizhi; Mak, Chun Hin; You, Peng; Mak, Chee Leung; Yan, Feng

    2015-02-06

    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.

  3. 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.

  4. Periodically porous top electrodes on vertical nanowire arrays for highly sensitive gas detection.

    PubMed

    In, Hyun Jin; Field, Christopher R; Pehrsson, Pehr E

    2011-09-02

    Nanowires of various materials and configurations have been shown to be highly effective in the detection of chemical and biological species. In this paper, we report a novel, nanosphere-enabled approach to fabricating highly sensitive gas sensors based on ordered arrays of vertically aligned silicon nanowires topped with a periodically porous top electrode. The vertical array configuration helps to greatly increase the sensitivity of the sensor while the pores in the top electrode layer significantly improve sensing response times by allowing analyte gases to pass through freely. Herein, we show highly sensitive detection to both nitrogen dioxide (NO(2)) and ammonia (NH(3)) in humidified air. NO(2) detection down to 10 parts per billion (ppb) is demonstrated and an order-of-magnitude improvement in sensor response time is shown in the detection of NH(3).

  5. Ringing phenomenon in chaotic microcavity for high-speed ultra-sensitive sensing

    PubMed Central

    Chen, Lei; Liu, Qian; Zhang, Wei-Gang; Chou, Keng C.

    2016-01-01

    The ringing phenomenon in whispering-gallery-mode (WGM) microcavities has demonstrated its great potential for highly-sensitive and high-speed sensing. However, traditional symmetric WGM microcavities have suffered from an extremely low coupling efficiency via free-space coupling because the emission of symmetric WGMs is non-directional. Here we report a new approach for high-speed ultra-sensitive sensing using the ringing phenomenon in a chaotic regime. By breaking the rotational symmetry of a WGM microcavity and introducing chaotic behaviors, we show that the ringing phenomenon in chaotic WGM microcavities extends over both the positive and the negative frequency detune, allowing the ringing phenomenon to interact with analytes over a much broader bandwidth with a reduced dead time. Because the coupling of the chaotic microcavity is directional, it produces a significantly higher signal output, which improves its sensitivity without the need of a fiber coupler. PMID:27966591

  6. 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.

  7. A Highly Sensitive CMOS Digital Hall Sensor for Low Magnetic Field Applications

    PubMed Central

    Xu, Yue; Pan, Hong-Bin; He, Shu-Zhuan; Li, Li

    2012-01-01

    Integrated CMOS Hall sensors have been widely used to measure magnetic fields. However, they are difficult to work with in a low magnetic field environment due to their low sensitivity and large offset. This paper describes a highly sensitive digital Hall sensor fabricated in 0.18 μm high voltage CMOS technology for low field applications. The sensor consists of a switched cross-shaped Hall plate and a novel signal conditioner. It effectively eliminates offset and low frequency 1/f noise by applying a dynamic quadrature offset cancellation technique. The measured results show the optimal Hall plate achieves a high current related sensitivity of about 310 V/AT. The whole sensor has a remarkable ability to measure a minimum ±2 mT magnetic field and output a digital Hall signal in a wide temperature range from −40 °C to 120 °C. PMID:22438758

  8. Wavelength-encoded fiber-optic temperature sensor with ultra-high sensitivity

    NASA Astrophysics Data System (ADS)

    Li, Enbang; Peng, Gang-Ding

    2008-12-01

    We present in this paper a wavelength-encoded fiber-optic temperature sensor with ultra-high sensitivity. The sensor consists of a segment of multimode fiber (MMF) with a polymer cladding spliced between two single mode fibers, forming a multimode fiber interferometer. For a temperature sensor with a 55 mm long MMF and a 45 mm long polymer cladding, a temperature sensitivity of -3.195 nm/°C has been achieved over a temperature range of 10 °C which is mainly limited by the spectral range of the light source used in the experiments. It has been found that the high temperature sensitivity is mainly attributed to the high thermo-optic coefficient of the polymer cladding. Other advantages of the temperature sensor reported here include its extremely simple structure and fabrication process, and hence a very low cost.

  9. 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.

  10. 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

    2015-12-07

    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.

  11. Ultra-high sensitivity photodetector arrays with integrated amplification and passivation nano-layers

    NASA Astrophysics Data System (ADS)

    Yao, Jie; Mokina, Irina A.; Liu, Feng; Wang, Sean; Zhou, Jack; Lange, Michael; Yang, Weiguo; Gardner, Patrick; Peltz, Leora; Frampton, Robert; Hunt, Jeffrey H.

    2010-02-01

    Miniaturized field-deployable spectrometers used for the rapid analysis of chemical and biological substances require high-sensitivity photo detectors. For example, in a Raman spectroscopy system, the receiver must be capable of high-gain, low-noise detection performance due to the intrinsically weak signals produced by the Raman effects of most substances. We are developing a novel, high-gain hetero-junction phototransistor (HPT) detector which employs two nano-structures simultaneously to achieve 100 times higher sensitivity than InGaAs avalanche photodiodes, the most sensitive commercially available photo-detector in the near infrared (NIR) wavelength range, under their normal operation conditions. Integrated into a detector array, this technology has application for Laser-Induced Breakdown Spectroscopy (LIBS), pollution monitoring, pharmaceutical manufacturing by reaction monitoring, chemical & biological transportation safety, and bio-chemical analysis in planetary exploration.

  12. A highly sensitive CMOS digital Hall sensor for low magnetic field applications.

    PubMed

    Xu, Yue; Pan, Hong-Bin; He, Shu-Zhuan; Li, Li

    2012-01-01

    Integrated CMOS Hall sensors have been widely used to measure magnetic fields. However, they are difficult to work with in a low magnetic field environment due to their low sensitivity and large offset. This paper describes a highly sensitive digital Hall sensor fabricated in 0.18 μm high voltage CMOS technology for low field applications. The sensor consists of a switched cross-shaped Hall plate and a novel signal conditioner. It effectively eliminates offset and low frequency 1/f noise by applying a dynamic quadrature offset cancellation technique. The measured results show the optimal Hall plate achieves a high current related sensitivity of about 310 V/AT. The whole sensor has a remarkable ability to measure a minimum ± 2 mT magnetic field and output a digital Hall signal in a wide temperature range from -40 °C to 120 °C.

  13. Optical transitions in highly charged californium ions with high sensitivity to variation of the fine-structure constant.

    PubMed

    Berengut, J C; Dzuba, V A; Flambaum, V V; Ong, A

    2012-08-17

    We study electronic transitions in highly charged Cf ions that are within the frequency range of optical lasers and have very high sensitivity to potential variations in the fine-structure constant, α. The transitions are in the optical range despite the large ionization energies because they lie on the level crossing of the 5f and 6p valence orbitals in the thallium isoelectronic sequence. Cf(16+) is a particularly rich ion, having several narrow lines with properties that minimize certain systematic effects. Cf(16+) has very large nuclear charge and large ionization energy, resulting in the largest α sensitivity seen in atomic systems. The lines include positive and negative shifters.

  14. Optical Transitions in Highly Charged Californium Ions with High Sensitivity to Variation of the Fine-Structure Constant

    NASA Astrophysics Data System (ADS)

    Berengut, J. C.; Dzuba, V. A.; Flambaum, V. V.; Ong, A.

    2012-08-01

    We study electronic transitions in highly charged Cf ions that are within the frequency range of optical lasers and have very high sensitivity to potential variations in the fine-structure constant, α. The transitions are in the optical range despite the large ionization energies because they lie on the level crossing of the 5f and 6p valence orbitals in the thallium isoelectronic sequence. Cf16+ is a particularly rich ion, having several narrow lines with properties that minimize certain systematic effects. Cf16+ has very large nuclear charge and large ionization energy, resulting in the largest α sensitivity seen in atomic systems. The lines include positive and negative shifters.

  15. Effects of intrinsic magnetostriction on tube-topology magnetoelectric sensors with high magnetic field sensitivity

    SciTech Connect

    Gillette, Scott M.; Fitchorov, Trifon; Obi, Ogheneyunume; Chen, Yajie Harris, Vincent G.; Jiang, Liping; Hao, Hongbo; Wu, Shuangxia

    2014-05-07

    Three quasi-one-dimensional magnetoelectric (ME) magnetic field sensors, each with a different magnetostrictive wire material, were investigated in terms of sensitivity and noise floor. Magnetostrictive Galfenol, iron-cobalt-vanadium, and iron-nickel wires were examined. Sensitivity profiles, hysteresis effects, and noise floor measurements for both optimally biased and zero-biased conditions are presented. The FeNi wire (FN) exhibits high sensitivity (5.36 mV/Oe) at bias fields below 22 Oe and an optimal bias of 10 Oe, whereas FeGa wire (FG) exhibits higher sensitivity (6.89 mW/Oe) at bias fields >22 Oe. The sensor of FeCoV wire (FC) presents relatively low sensitivity (2.12 mV/Oe), due to low magnetostrictive coefficient. Each ME tube-topology sensor demonstrates relatively high sensitivity at zero bias field, which results from a magnetic shape anisotropy and internal strain of the thin magnetostrictive wire.

  16. Highly Sensitive and Selective Ethanol Sensor Fabricated with In-Doped 3DOM ZnO.

    PubMed

    Wang, Zhihua; Tian, Ziwei; Han, Dongmei; Gu, Fubo

    2016-03-02

    ZnO is an important n-type semiconductor sensing material. Currently, much attention has been attracted to finding an effective method to prepare ZnO nanomaterials with high sensing sensitivity and excellent selectivity. A three-dimensionally ordered macroporous (3DOM) ZnO nanostructure with a large surface area is beneficial to gas and electron transfer, which can enhance the gas sensitivity of ZnO. Indium (In) doping is an effective way to improve the sensing properties of ZnO. In this paper, In-doped 3DOM ZnO with enhanced sensitivity and selectivity has been synthesized by using a colloidal crystal templating method. The 3DOM ZnO with 5 at. % of In-doping exhibits the highest sensitivity (∼88) to 100 ppm ethanol at 250 °C, which is approximately 3 times higher than that of pure 3DOM ZnO. The huge improvement to the sensitivity to ethanol was attributed to the increase in the surface area and the electron carrier concentration. The doping by In introduces more electrons into the matrix, which is helpful for increasing the amount of adsorbed oxygen, leading to high sensitivity. The In-doped 3DOM ZnO is a promising material for a new type of ethanol sensor.

  17. High open circuit voltages of solar cells based on quantum dot and dye hybrid-sensitization

    SciTech Connect

    Zhao, Yujie; Zhao, Wanyu; Chen, Jingkuo; Li, Huayang; Fu, Wuyou E-mail: fuwy56@163.com; Sun, Guang; Cao, Jianliang; Zhang, Zhanying; Bala, Hari E-mail: fuwy56@163.com

    2014-01-06

    A type of solar cell based on quantum dot (QD) and dye hybrid-sensitized mesoporous TiO{sub 2} film electrode was designed and reported. The electrode was consisted of a TiO{sub 2} nanoparticle (NP) thin film layer sensitized with CdS quantum dot (QD) and an amorphous TiO{sub 2} coated TiO{sub 2} NP thin film layer that sensitized with C106 dye. The amorphous TiO{sub 2} layer was obtained by TiCl{sub 4} post-treatment to improve the properties of solar cells. Research showed that the solar cells fabricated with as-prepared hybrid-sensitized electrode exhibited excellent photovoltaic performances and a fairly high open circuit voltage of 796 mV was achieved.

  18. High-sensitivity strain sensor based on in-fiber rectangular air bubble

    PubMed Central

    Liu, Shen; Yang, Kaiming; Wang, Yiping; Qu, Junle; Liao, Changrui; He, Jun; Li, Zhengyong; Yin, Guolu; Sun, Bing; Zhou, Jiangtao; Wang, Guanjun; Tang, Jian; Zhao, Jing

    2015-01-01

    We demonstrated a unique rectangular air bubble by means of splicing two sections of standard single mode fibers together and tapering the splicing joint. Such an air bubble can be used to develop a promising high-sensitivity strain sensor based on Fabry-Perot interference. The sensitivity of the strain sensor with a cavity length of about 61 μm and a wall thickness of about 1 μm was measured to be up to 43.0 pm/με and is the highest strain sensitivity among the in-fiber FPI-based strain sensors with air cavities reported so far. Moreover, our strain sensor has a very low temperature sensitivity of about 2.0 pm/°C. Thus, the temperature-induced strain measurement error is less than 0.046 με/°C. PMID:25557614

  19. Highly sensitive assay for phenylethanolamine N-methyltransferase in human brain

    SciTech Connect

    Burke, W.J.; Hanson, D.M.; Chung, H.D.

    1986-01-01

    A rapid, highly sensitive assay for phenylethanolamine N-methyltransferase in brain using the natural substrate, norepinephrine, is described. The method is based on the selective adsorption and elution of the reaction product, epinephrine, from alumina. A small but important further lowering of blanks and increase in sensitivity is attained by removal of the radiolabeled substrate, (methyl-/sup 3/H)-S-adenosylmethionine by precipitation as the reineckate prior to adsorption of norepinephrine to alumina. The assay has a sensitivity of 30 fmole and the PNMT activity could be measured in as little as 1 mg (wet wt) of human locus coeruleus tissue. The sensitivity is enhanced by homogenizing tissue in small volumes and removing potential inhibitors by dialysis. We report for the first time PNMT activity in specific regions of the human cerebral and cerebellar cortex.

  20. High-sensitivity strain sensor based on in-fiber rectangular air bubble.

    PubMed

    Liu, Shen; Yang, Kaiming; Wang, Yiping; Qu, Junle; Liao, Changrui; He, Jun; Li, Zhengyong; Yin, Guolu; Sun, Bing; Zhou, Jiangtao; Wang, Guanjun; Tang, Jian; Zhao, Jing

    2015-01-05

    We demonstrated a unique rectangular air bubble by means of splicing two sections of standard single mode fibers together and tapering the splicing joint. Such an air bubble can be used to develop a promising high-sensitivity strain sensor based on Fabry-Perot interference. The sensitivity of the strain sensor with a cavity length of about 61 μm and a wall thickness of about 1 μm was measured to be up to 43.0 pm/με and is the highest strain sensitivity among the in-fiber FPI-based strain sensors with air cavities reported so far. Moreover, our strain sensor has a very low temperature sensitivity of about 2.0 pm/°C. Thus, the temperature-induced strain measurement error is less than 0.046 με/°C.

  1. Environmental toxicology: population modeling of cod larvae shows high sensitivity to loss of zooplankton prey.

    PubMed

    Stige, Leif Christian; Ottersen, Geir; Hjermann, Dag Ø; Dalpadado, Padmini; Jensen, Louise K; Stenseth, Nils Chr

    2011-02-01

    Two factors determine whether pollution is likely to affect a population indirectly through loss of prey: firstly, the sensitivity of the prey to the pollutants, and secondly, the sensitivity of the predator population to loss of prey at the given life stage. We here apply a statistical recruitment model for Northeast Arctic cod to evaluate the sensitivity of cod cohorts to loss of zooplankton prey, for example following an oil spill. The calculations show that cod cohorts are highly sensitive to possible zooplankton biomass reductions in the distribution area of the cod larvae, and point to a need for more knowledge about oil-effects on zooplankton. Our study illustrates how knowledge about population dynamics may guide which indirect effects to consider in environmental impact studies.

  2. A small high sensitivity neutron detector using a wavelength shifting fiber.

    PubMed

    Yagi, T; Misawa, T; Pyeon, C H; Shiroya, S

    2011-01-01

    A small neutron detector using an optical fiber was previously developed for reaction rate measurements at research reactors and accelerator facilities. This detector can be inserted into narrow spaces and its spatial resolution is less than 1mm; however, its neutron sensitivity is low because of the small size of its detector. The purpose of this study is to develop a new optical fiber detector with high neutron sensitivity by using a wavelength shifting fiber. Through the measurement of the reaction rate distribution in a reactor core, we found that it is possible to increase the effective length of the detector, resulting in increased neutron sensitivity compared with a conventional optical fiber detector. Additionally, using a longer wavelength shifting fiber, the sensitivity can be increased until it is as large as that of a typical small BF(3) proportional counter, which means that this detector can be used for even low neutron flux fields.

  3. High-Sensitivity X-ray Polarimetry with Amorphous Silicon Active-Matrix Pixel Proportional Counters

    NASA Technical Reports Server (NTRS)

    Black, J. K.; Deines-Jones, P.; Jahoda, K.; Ready, S. E.; Street, R. A.

    2003-01-01

    Photoelectric X-ray polarimeters based on pixel micropattern gas detectors (MPGDs) offer order-of-magnitude improvement in sensitivity over more traditional techniques based on X-ray scattering. This new technique places some of the most interesting astronomical observations within reach of even a small, dedicated mission. The most sensitive instrument would be a photoelectric polarimeter at the focus of 2 a very large mirror, such as the planned XEUS. Our efforts are focused on a smaller pathfinder mission, which would achieve its greatest sensitivity with large-area, low-background, collimated polarimeters. We have recently demonstrated a MPGD polarimeter using amorphous silicon thin-film transistor (TFT) readout suitable for the focal plane of an X-ray telescope. All the technologies used in the demonstration polarimeter are scalable to the areas required for a high-sensitivity collimated polarimeter. Leywords: X-ray polarimetry, particle tracking, proportional counter, GEM, pixel readout

  4. Highly sensitive bending sensor based on multimode-multimode-coreoffset fiber structure

    NASA Astrophysics Data System (ADS)

    Qi, Yanhui; Ma, Lin; Sun, Jiang; Kang, Zexin; Bai, Yunlong; Jian, Shuisheng

    2015-12-01

    In this paper, we present a simple fiber optic bending sensor based on the multimode-multimode structure combining with the core-offset fiber structure. The multimode-multimode structure is composed of no core fiber (NCF) with hundreds of micrometers in length as a micro-lens for mode conversion, and single mode fiber (SMF) which can be seen as a section of special multimode fiber (MMF) when considered the cladding modes. The transmission spectrum in the experiment agrees well with the numerical model. The sensitivity of the structure can be achieved as high as 11.104 nm/m-1 in the measuring range. Meanwhile, the sensitivity of the neighboring resonance wavelength around 1546 nm exhibits approximately the same sensitivity which is 10.579 nm/m-1. Besides, the strain sensitivity is about -0.927 pm/με within the measuring strain range.

  5. Deep-UV-sensitive high-frame-rate backside-illuminated CCD camera developments

    NASA Astrophysics Data System (ADS)

    Dawson, Robin M.; Andreas, Robert; Andrews, James T.; Bhaskaran, Mahalingham; Farkas, Robert; Furst, David; Gershstein, Sergey; Grygon, Mark S.; Levine, Peter A.; Meray, Grazyna M.; O'Neal, Michael; Perna, Steve N.; Proefrock, Donald; Reale, Michael; Soydan, Ramazan; Sudol, Thomas M.; Swain, Pradyumna K.; Tower, John R.; Zanzucchi, Pete

    2002-04-01

    New applications for ultra-violet imaging are emerging in the fields of drug discovery and industrial inspection. High throughput is critical for these applications where millions of drug combinations are analyzed in secondary screenings or high rate inspection of small feature sizes over large areas is required. Sarnoff demonstrated in1990 a back illuminated, 1024 X 1024, 18 um pixel, split-frame-transfer device running at > 150 frames per second with high sensitivity in the visible spectrum. Sarnoff designed, fabricated and delivered cameras based on these CCDs and is now extending this technology to devices with higher pixel counts and higher frame rates through CCD architectural enhancements. The high sensitivities obtained in the visible spectrum are being pushed into the deep UV to support these new medical and industrial inspection applications. Sarnoff has achieved measured quantum efficiencies > 55% at 193 nm, rising to 65% at 300 nm, and remaining almost constant out to 750 nm. Optimization of the sensitivity is being pursued to tailor the quantum efficiency for particular wavelengths. Characteristics of these high frame rate CCDs and cameras will be described and results will be presented demonstrating high UV sensitivity down to 150 nm.

  6. Real-time, single-step bioassay using nanoplasmonic resonator with ultra-high sensitivity

    DOEpatents

    Zhang, Xiang; Ellman, Jonathan A; Chen, Fanqing Frank; Su, Kai-Hang; Wei, Qi-Huo; Sun, Cheng

    2014-04-01

    A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

  7. Highly Sensitive Colorimetric Detection of Ochratoxin A by a Label-Free Aptamer and Gold Nanoparticles

    PubMed Central

    Luan, Yunxia; Chen, Jiayi; Li, Cheng; Xie, Gang; Fu, Hailong; Ma, Zhihong; Lu, Anxiang

    2015-01-01

    A label-free aptamer-based assay for the highly sensitive and specific detection of Ochratoxin A (OTA) was developed using a cationic polymer and gold nanoparticles (AuNPs). The OTA aptamer was used as a recognition element for the colorimetric detection of OTA based on the aggregation of AuNPs by the cationic polymer. By spectroscopic quantitative analysis, the colorimetric assay could detect OTA down to 0.009 ng/mL with high selectivity in the presence of other interfering toxins. This study offers a new alternative in visual detection methods that is rapid and sensitive for OTA detection. PMID:26690477

  8. Highly Sensitive Colorimetric Detection of Ochratoxin A by a Label-Free Aptamer and Gold Nanoparticles.

    PubMed

    Luan, Yunxia; Chen, Jiayi; Li, Cheng; Xie, Gang; Fu, Hailong; Ma, Zhihong; Lu, Anxiang

    2015-12-10

    A label-free aptamer-based assay for the highly sensitive and specific detection of Ochratoxin A (OTA) was developed using a cationic polymer and gold nanoparticles (AuNPs). The OTA aptamer was used as a recognition element for the colorimetric detection of OTA based on the aggregation of AuNPs by the cationic polymer. By spectroscopic quantitative analysis, the colorimetric assay could detect OTA down to 0.009 ng/mL with high selectivity in the presence of other interfering toxins. This study offers a new alternative in visual detection methods that is rapid and sensitive for OTA detection.

  9. Seed oil polyphenols: rapid and sensitive extraction method and high resolution-mass spectrometry identification.

    PubMed

    Koubaa, Mohamed; Mhemdi, Houcine; Vorobiev, Eugène

    2015-05-01

    Phenolic content is a primary parameter for vegetables oil quality evaluation, and directly involved in the prevention of oxidation and oil preservation. Several methods have been reported in the literature for polyphenols extraction from seed oil but the approaches commonly used remain manually handled. In this work, we propose a rapid and sensitive method for seed oil polyphenols extraction and identification. For this purpose, polyphenols were extracted from Opuntia stricta Haw seed oil, using high frequency agitation, separated, and then identified using a liquid chromatography-high resolution mass spectrometry method. Our results showed good sensitivity and reproducibility of the developed methods.

  10. The coordination of allocation: Logistics of kidney organ allocation to highly sensitized patients.

    PubMed

    Lunz, John; Hinsdale, Lisa; King, Casey; Pastush, Robin; Buenvenida, Magnolia; Harmon, Michael

    2017-01-01

    Since implementation, the new UNOS OPTN kidney allocation system (KAS) has drastically expanded the pool of available kidneys to candidates that may have previously waited extended periods for an organ offer. This is particularly true for highly sensitized patients. The changes to the KAS have had ramifications throughout the transplant process, including for organ procurement organizations (OPO) and local transplant hospital call centers. Here, we will examine the impact of the new KAS on the organ donation process and highlight the necessary interactions between the OPO and transplant centers to best match donor kidneys and highly sensitized recipients.

  11. Real-Time, Single-Step Bioassay Using Nanoplasmonic Resonator With Ultra-High Sensitivity

    NASA Technical Reports Server (NTRS)

    Zhang, Xiang (Inventor); Ellman, Jonathan A. (Inventor); Chen, Fanqing Frank (Inventor); Su, Kai-Hang (Inventor); Wei, Qi-Huo (Inventor); Sun, Cheng (Inventor)

    2014-01-01

    A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

  12. Formation of High-Purity Indium Oxide Nanoparticles and Their Application to Sensitive Detection of Ammonia

    PubMed Central

    Bhardwaj, Sanjeev K.; Bhardwaj, Neha; Kukkar, Manil; Sharma, Amit L.; Kim, Ki-Hyun; Deep, Akash

    2015-01-01

    High-purity In2O3 nanoparticles were recovered from scrap indium tin oxide substrates in a stepwise process involving acidic leaching, liquid-liquid extraction with a phosphine oxide extractant, and combustion of the organic phase. The morphological and structural parameters of the recovered nanoparticles were investigated to support the formation of the desired products. These In2O3 nanoparticles were used for sensitive sensing of ammonia gas using a four-probe electrode device. The proposed sensor offered very quick response time (around 10 s) and highly sensitive detection of ammonia (at a detection limit of 1 ppm). PMID:26694415

  13. Depth-resolved holographic optical coherence imaging using a high-sensitivity photorefractive polymer device

    NASA Astrophysics Data System (ADS)

    Salvador, M.; Prauzner, J.; Köber, S.; Meerholz, K.; Jeong, K.; Nolte, D. D.

    2008-12-01

    We present coherence-gated holographic imaging using a highly sensitive photorefractive (PR) polymer composite as the recording medium. Due to the high sensitivity of the composite holographic recording at intensities as low as 5 mW/cm2 allowed for a frame exposure time of only 500ms. Motivated by regenerative medical applications, we demonstrate optical depth sectioning of a polymer foam for use as a cell culture matrix. An axial resolution of 18 μm and a transverse resolution of 30 μm up to a depth of 600 μm was obtained using an off-axis recording geometry.

  14. Localized brain differences in Arc expression between mice showing low vs. high propensity to ethanol sensitization.

    PubMed

    Nona, Christina N; Lam, Marcus; Nobrega, José N

    2016-03-01

    Behavioral sensitization to ethanol (EtOH) manifests as a progressive and enduring increase in locomotor activity with repeated drug exposure. However, not all mice sensitize to EtOH and the neuronal mechanisms mediating vulnerability and resistance to EtOH sensitization remain unclear. We examined regional brain expression of the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) in order to identify brain areas in which neuroplastic changes may contribute to the development and expression of EtOH sensitization. Male DBA/2J mice received 5 biweekly injections of EtOH (2.2g/kg, i.p.) or saline (SAL). They were categorized as high- (HS) or low-sensitized (LS) on the basis of final locomotor activity scores. In both LS and HS mice sacrificed after the last sensitization injection, Arc expression was decreased throughout the brain in comparison to SAL animals. A similar pattern was seen in mice sacrificed after an EtOH challenge two weeks after the last sensitization injection. However in this cohort, Arc expression was significantly increased in the central amygdala (CeA) in LS mice and in SAL mice receiving EtOH for the first time. No significant increases in Arc expression were seen in brains of sensitized (HS) animals. These results indicate an acute EtOH challenge results in different patterns of Arc expression in brains of LS, HS, and SAL mice. The dramatic increases in Arc expression in the CeA in LS and SAL mice showing little or no behavioral activation suggests that neural activity in this region may serve to inhibit the stimulant effects of EtOH. The observation that HS mice do not show increases in Arc expression with an EtOH challenge suggests the possibility that increased tolerance to the Arc-inducing effects of EtOH may be a factor in behavioral sensitization.

  15. Engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens

    NASA Astrophysics Data System (ADS)

    Seo, Youngmin; Kim, Ji-Eun; Jeong, Yoon; Lee, Kwan Hong; Hwang, Jangsun; Hong, Jongwook; Park, Hansoo; Choi, Jonghoon

    2016-01-01

    Many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. Given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Vaccinia virus) is highly desirable. Here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capturing antibodies against four different high-risk pathogens for simple and rapid isolation, and (2) genetically engineered apoferritin nanoparticles conjugated with multiple quantum dots and detection antibodies against four different high-risk pathogens for signal amplification. For each high-risk pathogen, we demonstrated at least 10-fold increase in sensitivity compared to traditional lateral flow devices that utilize enzyme-based detection methods. Multiplexed detection of high-risk pathogens in a sample was also successful by using the nanoconstructs harboring the dye molecules with fluorescence at different wavelengths. We ultimately envision the use of this novel nanoprobe detection platform in future applications that require highly sensitive on-site detection of high-risk pathogens.

  16. High-sensitivity sucrose erbium-doped fiber ring laser sensor

    NASA Astrophysics Data System (ADS)

    Khaleel, Wurood Abdulkhaleq; Al-Janabi, Abdul Hadi M.

    2017-02-01

    We investigate a high-sensitivity sucrose sensor based on a standard erbium-doped fiber ring laser incorporating a coreless fiber (CF). A single-mode-coreless-single mode (SCS) structure with a very low insertion loss has been constructed. The SCS fiber structure performed dual function as an intracavity fiber filter and/or a sensing element. The gain medium (erbium-doped fiber) is pumped by a 975-nm wavelength fiber coupled diode laser. Laser emission around 1537 nm with -2 dBm peak output power is obtained when a CF in SCS structure has a diameter of 125 μm. The 3-dB line-width of the laser is <0.14 nm, which is beneficial to high precision sensing. The sucrose concentration varied from 0% to 60%, and the relationship between the lasing wavelength and the sucrose concentration exhibited linear behavior (R2=0.996), with sensitivity of 0.16 nm/% was obtained. To improve the measurement sensitivity, the CF is etched by hydrofluoric acid. The splice joint of etched CF with SMF is a taper, which improves its sensitivity to sucrose changes. An average sensitivity of 0.57 nm/% and a high signal-to-noise ratio of 50 dB make the proposed sensor suitable for potential applications.

  17. Highly sensitive curvature sensor based on asymmetrical twin core fiber and multimode fiber

    NASA Astrophysics Data System (ADS)

    Wu, Yue; Pei, Li; Jin, Wenxing; Jiang, Youchao; Yang, Yuguang; Shen, Ya; Jian, Shuisheng

    2017-07-01

    A highly sensitive curvature sensor based on asymmetrical twin core fiber (TCF) and multimode fiber (MMF) is proposed and experimentally demonstrated. By applying the coupled-mode theory and equivalent refractive index model, we theoretically analyze the uncoupled feature of the TCF and the relationship between peak wavelength and the curvature. Two segments of MMF used as beam splitter and combiner are embedded on the two ends of the TCF, and the extinction ratio of the comb transmission spectrum is about 15 dB. The experimental result shows that the curvature sensitivity of the sensor can be achieved as high as 103.35 nm/m-1 ranging from 0.24 m-1 to 0.6 m-1, and the strain sensitivity is up to -4.01 pm/με in the range from 0 μεto 1400 με. The simultaneous detection of the curvature and strain can be realized. The temperature sensitivity is 0.431 nm/°C in the range from 40 °C to 70 °C. This fiber sensor exhibits the advantages of low cost, easy and repeated fabrication, and high sensitivity.

  18. High-speed and high-sensitivity parallel spectral-domain optical coherence tomography using a supercontinuum light source.

    PubMed

    Barrick, Jessica; Doblas, Ana; Gardner, Michael R; Sears, Patrick R; Ostrowski, Lawrence E; Oldenburg, Amy L

    2016-12-15

    The three most important metrics in optical coherence tomography (OCT) are resolution, speed, and sensitivity. Because there is a complex interplay between these metrics, no previous work has obtained the best performance in all three metrics simultaneously. We demonstrate that a high-power supercontinuum source, in combination with parallel spectral-domain OCT, achieves an unparalleled combination of resolution, speed, and sensitivity. This system captures cross-sectional images spanning 4  mm×0.5  mm at 1,024,000 lines/s with 2×14  μm resolution (axial×transverse) at a sensitivity of 113 dB. Imaging using the proposed system is demonstrated on highly differentiated human bronchial epithelial cells to capture and spatially localize ciliary dynamics.

  19. A novel light tracing system with high-precision and high-sensitivity sensors setup

    NASA Astrophysics Data System (ADS)

    Lin, Chern-Sheng; Wu, Pin Yi; Tsai, Jen Min; Tseng, Yu Hung; Chen, Hsin-Hung; Hwang, Jiann-Lih

    2013-11-01

    This paper presents a novel light source tracing system, which is comprised of a light-tracing board, with four photo-sensors of different incline angles, correspondingly disposed on its four edges, which are adjustable according to the movement range of the light source in order to achieve light-tracing purposes. This system introduces the algorithm of four-edge-sensors with servo motors in each site to improve sensor's sensitivity. The measurement values of light perception can be feedback to the programmable logic controller by wireless transceiver module. After proportional-integral-derivative operation, the system can obtain the situation of light source. In a normal mode, the light source movement range is large, the range of the incline angle of the light sensors are also set to large to obtain wide detection angle. But in a locking mode, the incline angle of the light sensing plane decreases, thus, the measurement range reduces, and the sensitivity is higher.

  20. The nature and nurture of high IQ: an extended sensitive period for intellectual development.

    PubMed

    Brant, Angela M; Munakata, Yuko; Boomsma, Dorret I; Defries, John C; Haworth, Claire M A; Keller, Matthew C; Martin, Nicholas G; McGue, Matthew; Petrill, Stephen A; Plomin, Robert; Wadsworth, Sally J; Wright, Margaret J; Hewitt, John K

    2013-08-01

    IQ predicts many measures of life success, as well as trajectories of brain development. Prolonged cortical thickening observed in individuals with high IQ might reflect an extended period of synaptogenesis and high environmental sensitivity or plasticity. We tested this hypothesis by examining the timing of changes in the magnitude of genetic and environmental influences on IQ as a function of IQ score. We found that individuals with high IQ show high environmental influence on IQ into adolescence (resembling younger children), whereas individuals with low IQ show high heritability of IQ in adolescence (resembling adults), a pattern consistent with an extended sensitive period for intellectual development in more-intelligent individuals. The pattern held across a cross-sectional sample of almost 11,000 twin pairs and a longitudinal sample of twins, biological siblings, and adoptive siblings.

  1. Surface plasmon resonance hydrogen sensor based on metallic grating with high sensitivity.

    PubMed

    Lin, Kaiqun; Lu, Yonghua; Chen, Junxue; Zheng, Rongsheng; Wang, Pei; Ming, Hai

    2008-11-10

    High sensitivity is obtained at larger resonant incident angle if negative diffraction order of metallic grating is used to excite the surface plasmon. A highly sensitive grating-based surface plasmon resonance (SPR) sensor is designed for the hydrogen detection. A thin palladium (Pd) film deposited on the grating surface is used as transducer. The influences of grating period and the thickness of Pd on the performance of sensor are investigated using rigorous coupled-wave analysis (RCWA) method. The sensitivity as well as the width of the SPR curves and reflective amplitude is considered simultaneously for designing the grating-based SPR hydrogen sensor, and a set of optimized structural parameters is presented. The performance of grating-based SPR sensor is also compared with that of conventional prism-based SPR sensor.

  2. A highly sensitive pressure sensor using conductive composite elastomers with wavy structures

    NASA Astrophysics Data System (ADS)

    Sun, Rujie; Zhang, Xiao-Chong; Rossiter, Jonathan; Scarpa, Fabrizio

    2016-05-01

    Flexible pressure sensors are crucial components for the next generation wearable devices to monitor human physiological conditions. In this paper, we present a novel resistive pressure sensor based on hybrid composites made from carbon nanotube (CNT) for the conductive coating layer and polydimethylsiloxane (PDMS) elastomers as the substrate. The high sensitivity of these sensors is attributed to the change of contact resistance caused by the variation of the contact areas between the wavy film and the electrodes. Porous electrodes were designed to increase the roughness of the interfaces, thus further enhancing the pressure sensitivity. The developed device was verified through a series of tests, and the sensor exhibited a high sensitivity of 2.05 kPa-1 under a low pressure of 35.6 Pa.

  3. Elucidation of high sensitivity of δ-HMX: New insight from first principles simulations

    NASA Astrophysics Data System (ADS)

    Kuklja, Maija M.; Tsyshevsky, Roman V.; Sharia, Onise

    2017-01-01

    Understanding of a significant difference in sensitivities of β and δ phases of cyclotetramethylene-tetranitramine (HMX) has been long one of the challenges in the field of high energy density materials. Despite many experimental and theoretical efforts to explain the high sensitivity of the δ phase, convincing reasons behind the HMX behavior remained unclear. We established that the presence of a polar surface in δ-HMX has fundamental implications for stability and overall chemical behavior of the material. A comparative quantum-chemical analysis of decomposition mechanisms in polar δ-HMX and nonpolar β-HMX discovered a considerable difference in dominating dissociation reactions, activation barriers, and reaction rates. The polarization-induced charge transfer offered a logical explanation for different sensitivity of β-HMX and δ-HMX polymorphs to detonation initiation. Our conclusions also removed long-standing contradictions and explained a large range of experimental data on thermal decomposition of HMX.

  4. A high sensitivity refractometer based on a tapered SCSMF structure and its application to biosensing

    NASA Astrophysics Data System (ADS)

    Wu, Qiang; Ma, Youqiao; Semenova, Yuliya; Yuan, Jinhui; Bo, Lin; Wang, Pengfei; Sang, Xinzhu; Teng, Mianzhen; Yu, Chongxiu; O'Mahony, Christy Charlton; Farrell, Gerald

    2014-05-01

    A high sensitivity refractive index (RI) sensor based on a tapered small core singlemode fibre (SCSMF) structure is proposed and developed. By tapering the SCSMF section, this sensor has very high sensitivity around the RI of water. Experimentally we have demonstrated a sensitivity of 1988.5 nm/RIU (RI unit) in the RI range from 1.3325 to 1.3407 by tapering a SCSMF section from a diameter of 125 μm to a diameter of 16 μm. The feasibility of using this type of sensor for biosensing application has also been verified by experiments. This was undertaken using a suitable Fibrinogen antigen surface functionalisation, which successfully showed that the sensor can in principle detect differences in the concentration of a Fibrinogen antibody.

  5. Highly soluble energy relay dyes for dye-sensitized solar cells.

    PubMed

    Margulis, George Y; Lim, Bogyu; Hardin, Brian E; Unger, Eva L; Yum, Jun-Ho; Feckl, Johann M; Fattakhova-Rohlfing, Dina; Bein, Thomas; Grätzel, Michael; Sellinger, Alan; McGehee, Michael D

    2013-07-21

    High solubility is a requirement for energy relay dyes (ERDs) to absorb a large portion of incident light and significantly improve the efficiency of dye-sensitized solar cells (DSSCs). Two benzonitrile-soluble ERDs, BL302 and BL315, were synthesized, characterized, and resulted in a 65% increase in the efficiency of TT1-sensitized DSSCs. The high solubility (180 mM) of these ERDs allows for absorption of over 95% of incident light at their peak wavelength. The overall power conversion efficiency of DSSCs with BL302 and BL315 was found to be limited by their energy transfer efficiency of approximately 70%. Losses due to large pore size, dynamic collisional quenching of the ERD, energy transfer to desorbed sensitizing dyes and static quenching by complex formation were investigated and it was found that a majority of the losses are caused by the formation of statically quenched ERDs in solution.

  6. High excitation transfer efficiency from energy relay dyes in dye-sensitized solar cells.

    PubMed

    Hardin, Brian E; Yum, Jun-Ho; Hoke, Eric T; Jun, Young Chul; Péchy, Peter; Torres, Tomás; Brongersma, Mark L; Nazeeruddin, Md Khaja; Grätzel, Michael; McGehee, Michael D

    2010-08-11

    The energy relay dye, 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM), was used with a near-infrared sensitizing dye, TT1, to increase the overall power conversion efficiency of a dye-sensitized solar cell (DSC) from 3.5% to 4.5%. The unattached DCM dyes exhibit an average excitation transfer efficiency (ETE) of 96% inside TT1-covered, mesostructured TiO(2) films. Further performance increases were limited by the solubility of DCM in an acetonitrile based electrolyte. This demonstration shows that energy relay dyes can be efficiently implemented in optimized dye-sensitized solar cells, but also highlights the need to design highly soluble energy relay dyes with high molar extinction coefficients.

  7. Mesoporous structured MIPs@CDs fluorescence sensor for highly sensitive detection of TNT.

    PubMed

    Xu, Shoufang; Lu, Hongzhi

    2016-11-15

    A facile strategy was developed to prepare mesoporous structured molecularly imprinted polymers capped carbon dots (M-MIPs@CDs) fluorescence sensor for highly sensitive and selective determination of TNT. The strategy using amino-CDs directly as "functional monomer" for imprinting simplify the imprinting process and provide well recognition sites accessibility. The as-prepared M-MIPs@CDs sensor, using periodic mesoporous silica as imprinting matrix, and amino-CDs directly as "functional monomer", exhibited excellent selectivity and sensitivity toward TNT with detection limit of 17nM. The recycling process was sustainable for 10 times without obvious efficiency decrease. The feasibility of the developed method in real samples was successfully evaluated through the analysis of TNT in soil and water samples with satisfactory recoveries of 88.6-95.7%. The method proposed in this work was proved to be a convenient and practical way to prepare high sensitive and selective fluorescence MIPs@CDs sensors.

  8. High IgE sensitization to maize and rice pollen in the highlands of Madagascar

    PubMed Central

    Ramavovololona; Sénéchal, Hélène; Andrianarisoa, Ange; Rakotoarimanana, Vololona; Godfrin, Dominique; Peltre, Gabriel; Poncet, Pascal; Sutra, Jean-Pierre

    2014-01-01

    Introduction Maize and rice are two crops constituting the main food supply in many under-developed and developing countries. Despite the large area devoted to the culture, the sensitization to the pollen from these plants is reported to be low and often considered as an occupational allergy. Methods Sixty five Malagasy pollen allergic patients were clinically and immunochemically investigated with regard to maize and rice pollen allergens. Pollen extracts were electrophoretically separated in 1 and 2 dimensions and IgE and IgG reactivities detected upon immunoblotting. Results When exploring the sensitization profile of Malagasy allergic patients to maize and rice pollen, it appears that a high proportion of these patients consulting during grass pollinating season were sensitized to both pollen as revealed by skin prick testing (62 vs. 59%) and IgE immunoblotting (85 vs. 40%). Several clinically relevant allergens were recognized by patients’ serum IgE in maize and rice pollen extracts. Conclusion The high levels of maize and rice pollen sensitization should be related, in this tropical region, to a specific environmental exposure including i) a proximity of the population to the allergenic sources and ii) a putative exacerbating effect of a highly polluted urban atmosphere on pollen allergenicity. Cross-reactivities between wild and cultivated grasses and also between rice and maize pollen are involved as well as some specific maize sensitizations. The presence of dense urban and peri-urban agriculture, in various African regions and worldwide, could be a high environmental risk factor for people sensitive to maize pollen. PMID:25870739

  9. Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis

    PubMed Central

    Schäfer, Miriam R.; Milleit, Berko; Langbein, Kerstin; Hipler, Uta-Christina; Milleit, Christine; Klier, Claudia M.; Schlögelhofer, Monika; Holub, Magdalena; Holzer, Ingrid; Berk, Michael; McGorry, Patrick D.; Sauer, Heinrich; Amminger, G. Paul

    2016-01-01

    Background Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. Methods We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics. Results Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. Conclusions Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated. PMID:26894921

  10. Highly sensitive and selective gold(I) recognition by a metalloregulator in Ralstonia metallidurans.

    PubMed

    Jian, Xing; Wasinger, Erik C; Lockard, Jenny V; Chen, Lin X; He, Chuan

    2009-08-12

    A MerR family metalloregulatory protein CupR selectively responds to gold stress in Ralstonia metallidurans. A distorted trigonal geometry appears to be used by CupR to achieve the highly sensitive (K(d) approximately 10(-35) M) and selective recognition of gold(I).

  11. Constructing a High-Sensitivity, Computer-Interfaced, Differential Thermal Analysis Device for Teaching and Research

    ERIC Educational Resources Information Center

    Martinez, L. M.; Videa, M.; Mederos, F.; Mesquita, J.

    2007-01-01

    The construction of a new highly-sensitive, computer-interfaced, differential thermal analysis (DTA) device, used for gathering different information about the chemical reactions, is described. The instrument provides a better understanding about the phase transitions, phase diagrams and many more concepts to the students.

  12. A New Kind of Laser Microphone Using High Sensitivity Pulsed Laser Vibrometer

    NASA Technical Reports Server (NTRS)

    Wang, Chen-Chia; Trivedi, Sudhir; Jin, Feng; Swaminathan, V.; Prasad, Narasimha S.

    2008-01-01

    We demonstrate experimentally a new kind of laser microphone using a highly sensitive pulsed laser vibrometer. By using the photo-electromotive-force (photo-EMF) sensors, we present data indicating the real-time detection of surface displacements as small as 4 pm.

  13. Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells.

    PubMed

    Shi, Qiuyan; Li, Yu; Bo, Shaowei; Li, Xiaofei; Zhao, Peng; Liu, Qi; Yang, Zhigang; Cong, Hengjiang; Deng, Hexiang; Chen, Mingnan; Chen, Shizhen; Zhou, Xin; Ding, Hong; Jiang, Zhong-Xing

    2016-04-14

    Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and (19)F MRI sensitivity was discovered as a novel theranostic agent.

  14. A very sensitive high-resolution NMR method for quadrupolar nuclei: SPAM-DQF-STMAS.

    PubMed

    Amoureux, Jean-Paul; Flambard, Alexandrine; Delevoye, Laurent; Montagne, Lionel

    2005-07-21

    We show that by combining the intrinsically larger (with respect to MQMAS) efficiency of Double-Quantum Filtered Satellite-Transition MAS (DQF-STMAS), with the large S/N gain of the Soft-Pulse Added Mixing (SPAM) concept, a new very sensitive high-resolution solid-state NMR method can be obtained for semi-integer quadrupolar nuclei.

  15. Luminescent metal-organic framework films as highly sensitive and fast-response oxygen sensors.

    PubMed

    Dou, Zhongshang; Yu, Jiancan; Cui, Yuanjing; Yang, Yu; Wang, Zhiyu; Yang, Deren; Qian, Guodong

    2014-04-16

    Luminescent metal-organic framework films, CPM-5⊃Tb(3+) and MIL-100(In)⊃Tb(3+), have been constructed by postfunctionalization of two porous indium-organic frameworks with different structures, respectively. The MIL-100(In)⊃Tb(3+) film shows high oxygen sensitivity (KSV = 7.59) and short response/recovery time (6 s/53 s).

  16. A Highly Sensitive Diketopyrrolopyrrole-Based Ambipolar Transistor for Selective Detection and Discrimination of Xylene Isomers.

    PubMed

    Wang, Bin; Huynh, Tan-Phat; Wu, Weiwei; Hayek, Naseem; Do, Thu Trang; Cancilla, John C; Torrecilla, Jose S; Nahid, Masrur Morshed; Colwell, John M; Gazit, Oz M; Puniredd, Sreenivasa Reddy; McNeill, Christopher R; Sonar, Prashant; Haick, Hossam

    2016-06-01

    An ambipolar poly(diketopyrrolopyrrole-terthiophene)-based field-effect transistor (FET) sensitively detects xylene isomers at low ppm levels with multiple sensing features. Combined with pattern-recognition algorithms, a sole ambipolar FET sensor, rather than arrays of sensors, can discriminate highly similar xylene structural isomers from one another.

  17. Carbonized Silk Fabric for Ultrastretchable, Highly Sensitive, and Wearable Strain Sensors.

    PubMed

    Wang, Chunya; Li, Xiang; Gao, Enlai; Jian, Muqiang; Xia, Kailun; Wang, Qi; Xu, Zhiping; Ren, Tianling; Zhang, Yingying

    2016-08-01

    A carbonized plain-weave silk fabric is fabricated into wearable and robust strain sensors, which can be stretched up to 500% and show high sensitivity in a wide strain range. This sensor can be assembled into wearable devices for detection of both large and subtle human activities, showing great potential for monitoring human motions and personal health.

  18. Highly efficient catalysts for Co(II/III) redox couples in dye-sensitized solar cells.

    PubMed

    Wang, Liang; Diau, Eric Wei-Guang; Wu, Mingxing; Lu, Hsueh-Pei; Ma, Tingli

    2012-03-07

    We developed several low-cost catalysts with high catalytic activity, which were used as counter electrodes in dye-sensitized solar cells (DSCs). They showed higher efficiencies than that of Pt. The efficiencies were improved by 18-42% for the DSCs composed of active carbon, niobium dioxide, ordered mesoporous carbon and commercial titanium carbide.

  19. The Anti-Matter Spectrometer for high sensitivity searches of anti-nuclei in space.

    NASA Astrophysics Data System (ADS)

    Wallraff, W.

    The apparent absence of antimatter (anti-helium, anti-carbon, etc.) in the universe is a major puzzle of particle physics. The Anti-Matter Spectrometer is a high resolution tracking detector under construction, that will improve the sensitivity for antimatter searches by a factor of more than 104, while orbiting around the Earth on the space station ISSA for >3 years.

  20. Real time detection of live microbes using a highly sensitive bioluminescent nitroreductase probe.

    PubMed

    Wong, Roger H F; Kwong, Thomas; Yau, Kwok-Hei; Au-Yeung, Ho Yu

    2015-03-14

    A highly sensitive and selective nitroreductase probe, showing a rapid and strong bioluminescence enhancement (>100-fold in 5 minutes), and its initial application in the real time detection of both Gram positive and Gram negative live bacteria and monitoring of their growth has been reported.