A novel bismuth-based lead-free piezoelectric transducer immunosensor for carbaryl quantification

[EN] A novel BNT-BKT-BT piezoelectric ceramic immunosensor, tested for quantification of the pesticide carbaryl is here presented. The measuring format was based on a competitive immunoassay of immobilized conjugate using monoclonal antibodies (MAbs) as specific immunoreagent. The immunosensor is able to detect concentrations of the analyte from one and up to three orders of magnitude below the reported values of high- and low- frequency quartz crystal commercial resonators (HFF-QCM and QCM), respectively. Furthermore, the minimum content of quantified carbaryl is 0.11 ¿g L-1, which is clearly lower than reported values of any commercial quartz-based biosensors. Such measurement characteristics are only possible due to the high electromechanical coupling factor (kt) of the Bi-based piezoelectric ceramic, approaching the commercial QCM, HFF-QCM and ELISA techniques and strongly enhancing the sensitivity of the immunoassay.This project received support from CONACYT (Grants Nr. CB-220734, FC 2015-2-896, LN 292686 and 293429). This work has been carried out at CENAPROT and LIDTRA national laboratories as well as at Center for Research and Innovation in Bioengineering (Ci2B) of Universitat Politecnica de Valencia.Fernández-Benavides, D.; Cervera-Chiner, L.; Jiménez Jiménez, Y.; Arias De Fuentes, O.; Montoya, Á.; Muñoz-Saldaña, J. (2019). A novel bismuth-based lead-free piezoelectric transducer immunosensor for carbaryl quantification. Sensors and Actuators B Chemical. 285:423-430. https://doi.org/10.1016/j.snb.2019.01.081S42343028

Data-driven reconstruction of chaotic dynamical equations: the H\'enon-Heiles type system

In this study, the classical two-dimensional potential $V_N=\frac{1}{2}\,m\,\omega^2\,r^2 + \frac{1}{N}\,r^N\,\sin(N\,\theta)$, $N \in {\mathbb Z}^+$, is considered. At $N=1,2$, the system is superintegrable and integrable, respectively, whereas for $N>2$ it exhibits a richer chaotic dynamics. For instance, at $N=3$ it coincides with the H\'enon-Heiles system. The periodic, quasi-periodic and chaotic motions are systematically characterized employing time series, Poincar\'e sections, symmetry lines and the largest Lyapunov exponent as a function of the energy $E$ and the parameter $N$. Concrete results for the lowest cases $N=3,4$ are presented in complete detail. This model is used as a benchmark system to estimate the accuracy of the Sparse Identification of Nonlinear Dynamical Systems (SINDy) method, a data-driven algorithm which reconstructs the underlying governing dynamical equations. We pay special attention at the transition from regular motion to chaos and how this influences the precision of the algorithm. In particular, it is shown that SINDy is a robust and stable tool possessing the ability to generate non-trivial approximate analytical expressions for periodic trajectories as well

Frequency-shift vs phase-shift characterization of in-liquid quartz crystal microbalance applications

The improvement of sensitivity in quartz crystal microbalance (QCM) applications has been addressed in the last decades by increasing the sensor fundamental frequency, following the increment of the frequencymass sensitivity with the square of frequency predicted by Sauerbrey. However, this sensitivity improvement has not been completely transferred in terms of resolution. The decrease of frequency stability due to the increase of the phase noise, particularly in oscillators, made impossible to reach the expected resolution. A new concept of sensor characterization at constant frequency has been recently proposed. The validation of the new concept is presented in this work. An immunosensor application for the detection of a low molecular weight contaminant, the insecticide carbaryl, has been chosen for the validation. An, in principle, improved version of a balanced-bridge oscillator is validated for its use in liquids, and applied for the frequency shift characterization of the QCM immunosensor application. The classical frequency shift characterization is compared with the new phase-shift characterization concept and system proposed. © 2011 American Institute of Physics.The authors are grateful to the Spanish Ministry of Science and Technology for the financial support to this research under contract reference AGL2009-13511, and to the company Advanced Wave Sensors S. L. (www.awsensors.com) for the help provided in the development of some parts of this work.Montagut Ferizzola, YJ.; García Narbón, JV.; Jiménez Jiménez, Y.; March Iborra, MDC.; Montoya Baides, Á.; Arnau Vives, A. (2011). Frequency-shift vs phase-shift characterization of in-liquid quartz crystal microbalance applications. Review of Scientific Instruments. 82(6):1-14. https://doi.org/10.1063/1.3598340S114826Sauerbrey, G. (1959). 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Biomacromolecules, 3(6), 1170-1178. doi:10.1021/bm0255490Höök, F., Ray, A., Nordén, B., & Kasemo, B. (2001). Characterization of PNA and DNA Immobilization and Subsequent Hybridization with DNA Using Acoustic-Shear-Wave Attenuation Measurements. Langmuir, 17(26), 8305-8312. doi:10.1021/la0107704Ben-Dov, I., Willner, I., & Zisman, E. (1997). Piezoelectric Immunosensors for Urine Specimens ofChlamydia trachomatisEmploying Quartz Crystal Microbalance Microgravimetric Analyses. Analytical Chemistry, 69(17), 3506-3512. doi:10.1021/ac970216sNirschl, M., Blüher, A., Erler, C., Katzschner, B., Vikholm-Lundin, I., Auer, S., … Mertig, M. (2009). Film bulk acoustic resonators for DNA and protein detection and investigation of in vitro bacterial S-layer formation. Sensors and Actuators A: Physical, 156(1), 180-184. doi:10.1016/j.sna.2009.02.021Fung, Y. S., & Wong, Y. Y. (2001). Self-Assembled Monolayers as the Coating in a Quartz Piezoelectric Crystal Immunosensor To Detect Salmonella in Aqueous Solution. Analytical Chemistry, 73(21), 5302-5309. doi:10.1021/ac010655yZhou, X., Liu, L., Hu, M., Wang, L., & Hu, J. (2002). Detection of hepatitis B virus by piezoelectric biosensor. Journal of Pharmaceutical and Biomedical Analysis, 27(1-2), 341-345. doi:10.1016/s0731-7085(01)00538-6Gabl, R., Green, E., Schreiter, M., Feucht, H. D., Zeininger, H., Primig, R., … Wersing, W. (s. f.). Novel integrated FBAR sensors: a universal technology platform for bio- and gas-detection. Proceedings of IEEE Sensors 2003 (IEEE Cat. No.03CH37498). doi:10.1109/icsens.2003.1279132Gabl, R., Feucht, H.-D., Zeininger, H., Eckstein, G., Schreiter, M., Primig, R., … Wersing, W. (2004). First results on label-free detection of DNA and protein molecules using a novel integrated sensor technology based on gravimetric detection principles. 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IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 53(11), 2095-2100. doi:10.1109/tuffc.2006.149Wingqvist, G., Bjurström, J., Liljeholm, L., Yantchev, V., & Katardjiev, I. (2007). Shear mode AlN thin film electro-acoustic resonant sensor operation in viscous media. Sensors and Actuators B: Chemical, 123(1), 466-473. doi:10.1016/j.snb.2006.09.028Wingqvist, G., Anderson, H., Lennartsson, C., Weissbach, T., Yantchev, V., & Lloyd Spetz, A. (2009). On the applicability of high frequency acoustic shear mode biosensing in view of thickness limitations set by the film resonance. Biosensors and Bioelectronics, 24(11), 3387-3390. doi:10.1016/j.bios.2009.04.021Harding, G. L. (2001). Mass sensitivity of Love-mode acoustic sensors incorporating silicon dioxide and silicon-oxy-fluoride guiding layers. Sensors and Actuators A: Physical, 88(1), 20-28. doi:10.1016/s0924-4247(00)00491-xWang, Z., Cheeke, J. D. N., & Jen, C. K. (1994). Sensitivity analysis for Love mode acoustic gravimetric sensors. Applied Physics Letters, 64(22), 2940-2942. doi:10.1063/1.111976Kalantar-Zadeh, K., Wlodarski, W., Chen, Y. Y., Fry, B. N., & Galatsis, K. (2003). Novel Love mode surface acoustic wave based immunosensors. Sensors and Actuators B: Chemical, 91(1-3), 143-147. doi:10.1016/s0925-4005(03)00079-0Ogi, H., Naga, H., Fukunishi, Y., Hirao, M., & Nishiyama, M. (2009). 170-MHz Electrodeless Quartz Crystal Microbalance Biosensor: Capability and Limitation of Higher Frequency Measurement. Analytical Chemistry, 81(19), 8068-8073. doi:10.1021/ac901267bA. Arnau, V. Ferrari, D. Soares, and H. Perrot, inPiezoelectric Transducers and Applications, edited by A. Arnau, 2nd ed. (Springer Verlag, Berlin Heidelberg, 2008), ch. 5, pp. 117–186.Eichelbaum, F., Borngräber, R., Schröder, J., Lucklum, R., & Hauptmann, P. (1999). Interface circuits for quartz-crystal-microbalance sensors. Review of Scientific Instruments, 70(5), 2537-2545. doi:10.1063/1.1149788Schröder, J., Borngräber, R., Lucklum, R., & Hauptmann, P. (2001). Network analysis based interface electronics for quartz crystal microbalance. Review of Scientific Instruments, 72(6), 2750-2755. doi:10.1063/1.1370560Doerner, S., Schneider, T., Schroder, J., & Hauptmann, P. (s. f.). Universal impedance spectrum analyzer for sensor applications. Proceedings of IEEE Sensors 2003 (IEEE Cat. No.03CH37498). doi:10.1109/icsens.2003.1279007Rodahl, M., & Kasemo, B. (1996). A simple setup to simultaneously measure the resonant frequency and the absolute dissipation factor of a quartz crystal microbalance. Review of Scientific Instruments, 67(9), 3238-3241. doi:10.1063/1.1147494Rodahl, M., & Kasemo, B. (1996). Frequency and dissipation-factor responses to localized liquid deposits on a QCM electrode. Sensors and Actuators B: Chemical, 37(1-2), 111-116. doi:10.1016/s0925-4005(97)80077-9Barnes, C. (1992). Some new concepts on factors influencing the operational frequency of liquid-immersed quartz microbalances. Sensors and Actuators A: Physical, 30(3), 197-202. doi:10.1016/0924-4247(92)80120-rWessendorf, K. O. (s. f.). The Lever oscillator for use in high resistance resonator applications. 1993 IEEE International Frequency Control Symposium. doi:10.1109/freq.1993.367466Borngraber, R., Schroder, J., Lucklum, R., & Hauptmann, P. (2002). Is an oscillator-based measurement adequate in a liquid environment? IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 49(9), 1254-1259. doi:10.1109/tuffc.2002.1041542Ehahoun, H., Gabrielli, C., Keddam, M., Perrot, H., & Rousseau, P. (2002). Performances and Limits of a Parallel Oscillator for Electrochemical Quartz Crystal Microbalances. Analytical Chemistry, 74(5), 1119-1127. doi:10.1021/ac010883sMartin, S. J., Spates, J. J., Wessendorf, K. O., Schneider, T. W., & Huber, R. J. (1997). Resonator/Oscillator Response to Liquid Loading. Analytical Chemistry, 69(11), 2050-2054. doi:10.1021/ac961194xFerrari, V., Marioli, D., & Taroni, A. (2001). Improving the accuracy and operating range of quartz microbalance sensors by a purposely designed oscillator circuit. IEEE Transactions on Instrumentation and Measurement, 50(5), 1119-1122. doi:10.1109/19.963169Arnau, A., Sogorb, T., & Jiménez, Y. (2002). Circuit for continuous motional series resonant frequency and motional resistance monitoring of quartz crystal resonators by parallel capacitance compensation. Review of Scientific Instruments, 73(7), 2724-2737. doi:10.1063/1.1484254Jakoby, B., Art, G., & Bastemeijer, J. (2005). Novel analog readout electronics for microacoustic thickness shear-mode sensors. IEEE Sensors Journal, 5(5), 1106-1111. doi:10.1109/jsen.2005.844330Ferrari, M., Ferrari, V., Marioli, D., Taroni, A., Suman, M., & Dalcanale, E. (2006). In-Liquid Sensing of Chemical Compounds by QCM Sensors Coupled With High-Accuracy ACC Oscillator. IEEE Transactions on Instrumentation and Measurement, 55(3), 828-834. doi:10.1109/tim.2006.873792Ferrari, M., Ferrari, V., & Kanazawa, K. K. (2008). Dual-harmonic oscillator for quartz crystal resonator sensors. Sensors and Actuators A: Physical, 145-146, 131-138. doi:10.1016/j.sna.2007.10.087Riesch, C., & Jakoby, B. (2007). Novel Readout Electronics for Thickness Shear-Mode Liquid Sensors Compensating for Spurious Conductivity and Capacitances. IEEE Sensors Journal, 7(3), 464-469. doi:10.1109/jsen.2007.891931Arnau, A., García, J. V., Jimenez, Y., Ferrari, V., & Ferrari, M. (2008). Improved electronic interfaces forAT-cut quartz crystal microbalance sensors under variable damping and parallel capacitance conditions. Review of Scientific Instruments, 79(7), 075110. doi:10.1063/1.2960571Barnes, C. (1991). Development of quartz crystal oscillators for under-liquid sensing. Sensors and Actuators A: Physical, 29(1), 59-69. doi:10.1016/0924-4247(91)80032-kAuge, J., Hauptmann, P., Eichelbaum, F., & Rösler, S. (1994). Quartz crystal microbalance sensor in liquids. Sensors and Actuators B: Chemical, 19(1-3), 518-522. doi:10.1016/0925-4005(93)00983-6Auge, J., Hauptmann, P., Hartmann, J., Rösler, S., & Lucklum, R. (1995). New design for QCM sensors in liquids. Sensors and Actuators B: Chemical, 24(1-3), 43-48. doi:10.1016/0925-4005(95)85010-4Chagnard, C., Gilbert, P., Watkins, A. N., Beeler, T., & Paul, D. W. (1996). An electronic oscillator with automatic gain control: EQCM applications. Sensors and Actuators B: Chemical, 32(2), 129-136. doi:10.1016/0925-4005(96)80121-3Rodriguez-Pardo, L., Fariña, J., Gabrielli, C., Perrot, H., & Brendel, R. (2004). Resolution in quartz crystal oscillator circuits for high sensitivity microbalance sensors in damping media. Sensors and Actuators B: Chemical, 103(1-2), 318-324. doi:10.1016/j.snb.2004.04.060Rodriguez-Pardo, L., Fariña, J., Gabrielli, C., Perrot, H., & Brendel, R. (2006). Quartz crystal oscillator circuit for high resolution microgravimetric sensors in fluids. Electronics Letters, 42(18), 1065. doi:10.1049/el:20061854Wessendorf, K. O. (s. f.). The active-bridge oscillator for use with liquid loaded QCM sensors. Proceedings of the 2001 IEEE International Frequncy Control Symposium and PDA Exhibition (Cat. No.01CH37218). doi:10.1109/freq.2001.956260E. Benes, M. Schmid, M. Gröschl, P. Berlinger, H. Nowotny, and K. C. Harms, Proceedings of the Joint Meeting of the European Frequency and Time Forum and the IEEE International Frequency Control Symposium, Vol. 2, p. 1023–1026 (1999).J. Rabe, S. Büttgenbach, B. Zimmermann, and P. Hauptmann, 2000 IEEE/EIA International Frequency Control Symposium and Exhibition, pp. 106–112 (2000).Uttenthaler, E., Schräml, M., Mandel, J., & Drost, S. (2001). Ultrasensitive quartz crystal microbalance sensors for detection of M13-Phages in liquids. Biosensors and Bioelectronics, 16(9-12), 735-743. doi:10.1016/s0956-5663(01)00220-2Zimmermann, B., Lucklum, R., Hauptmann, P., Rabe, J., & Büttgenbach, S. (2001). Electrical characterisation of high-frequency thickness-shear-mode resonators by impedance analysis. Sensors and Actuators B: Chemical, 76(1-3), 47-57. doi:10.1016/s0925-4005(01)00567-6Sagmeister, B. P., Graz, I. M., Schwödiauer, R., Gruber, H., & Bauer, S. (2009). User-friendly, miniature biosensor flow cell for fragile high fundamental frequency quartz crystal resonators. Biosensors and Bioelectronics, 24(8), 2643-2648. doi:10.1016/j.bios.2009.01.023Bustabad, E. A., Rose, D., Arnau, A., Garcia, G., Rodriguez-Pardo, L., Farina, J., … Lazerges, M. (2009). A biosensor for detection of DNA sequences based on a 50MHz QCM electronic oscillator circuit. 2009 IEEE Sensors. doi:10.1109/icsens.2009.5398346Arnau, A., Montagut, Y., García, J. V., & Jiménez, Y. (2009). A different point of view on the sensitivity of quartz crystal microbalance sensors. Measurement Science and Technology, 20(12), 124004. doi:10.1088/0957-0233/20/12/124004Martin, S. J., Granstaff, V. E., & Frye, G. C. (1991). Characterization of a quartz crystal microbalance with simultaneous mass and liquid loading. Analytical Chemistry, 63(20), 2272-2281. doi:10.1021/ac00020a015Keiji Kanazawa, K., & Gordon, J. G. (1985). The oscillation frequency of a quartz resonator in contact with liquid. Analytica Chimica Acta, 175, 99-105. doi:10.1016/s0003-2670(00)82721-xPax, M., Rieger, J., Eibl, R. H., Thielemann, C., & Johannsmann, D. (2005). Measurements of fast fluctuations of viscoelastic properties with the quartz crystal microbalance. The Analyst, 130(11), 1474. doi:10.1039/b504302fMontrose, M. I. (1998). EMC and the Printed Circuit Board. doi:10.1002/047172310xA. Montoya, A. Ocampo, and C. March, inPiezoelectric Transducers and Applications, edited by A. Arnau, 2nd ed. (Springer-Verlag, Berlin, Heidelberg, 2008), Ch 12, pp. 289–306.Abad, A., Primo, J., & Montoya, A. (1997). Development of an Enzyme-Linked Immunosorbent Assay to Carbaryl. 1. Antibody Production from Several Haptens and Characterization in Different Immunoassay Formats. Journal of Agricultural and Food Chemistry, 45(4), 1486-1494. doi:10.1021/jf9506904Soares, D. M. (1993). A quartz microbalance with the capability of viscoelasticity measurements for in situ electrochemical investigations. Measurement Science and Technology, 4(5), 549-553. doi:10.1088/0957-0233/4/5/001Fruböse, C., Doblhofer, K., & Soares, D. M. (1993). Impedance Analysis of the Quartz Micro-Balance Signal. Berichte der Bunsengesellschaft für physikalische Chemie, 97(3), 475-478. doi:10.1002/bbpc.1993097034

Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients

Introduction: In a previous study with 96 septic patients, we found that circulating platelets in 6-months surviving septic patients showed higher activity and quantity of cytochrome c oxidase (COX) normalized by citrate synthase (CS) activity at moment of severe sepsis diagnosis than non-surviving septic patients. The objective of this study was to estimate whether COX specific activity during the first week predicts 1-month sepsis survival in a larger cohort of patients.Methods: Using a prospective, multicenter, observational study carried out in six Spanish intensive care units with 198 severe septic patients, we determined COX activity per proteins (COXact/Prot) in circulating platelets at day 1, 4 and 8 of the severe sepsis diagnosis. Endpoints were 1-month and 6-months mortality.Results: Survivor patients (n = 130) showed higher COXact/Prot (P 0.30 mOD/min/mg at day 1 (P = 0.002), 4 (P = 0.006) and 8 (P = 0.02) was associated independently with 1-month mortality. Area under the curve of COXact/Prot at day 1, 4 and 8 to predict 30-day survival were 0.70 (95% CI = 0.63-0.76; P < 0.001), 0.71 (95% CI = 0.64-0.77; P < 0.001) and 0.71 (95% CI = 0.64-0.78; P < 0.001), respectively.Conclusions: The new findings of our study, to our knowledge the largest series reporting data about mitochondrial function during follow-up in septic patients, were that septic patients that survive 1-month have a higher platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week than non-survivors, and that platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week could be used as biomarker to predict the clinical outcome in septic patients

Drivers of the Ectoparasite Community and Co-Infection Patterns in Rural and Urban Burrowing Owls

We analyzed the ectoparasite community of a monomorphic and non-social bird, the burrowing owl, Athene cunicularia, breeding in rural and urban habitats. Such community was composed by two lice, one mite and one flea species. Rural individuals had more fleas and less mites than urban ones. Adult birds harbored less ectoparasites than young ones and females harbored more lice than males. The presence of lice was positively related to the presence of fleas. On the contrary, the presence of mites was negatively related to the presence of fleas and lice. The study of parasite communities in urban and rural populations of the same species can shed light on how urban stressor factors impact the physiology of wildlife inhabiting cities and, therefore, the host-parasite relationships. Urbanization creates new ecological conditions that can affect biodiversity at all levels, including the diversity and prevalence of parasites of species that may occupy these environments. However, few studies have compared bird-ectoparasite interactions between urban and rural individuals. Here, we analyze the ectoparasite community and co-infection patterns of urban and rural burrowing owls, Athene cunicularia, to assess the influence of host traits (i.e., sex, age, and weight), and environmental factors (i.e., number of conspecifics per nest, habitat type and aridity) on its composition. Ectoparasites of burrowing owls included two lice, one flea, and one mite. The overall prevalence for mites, lice and fleas was 1.75%, 8.76% and 3.50%, respectively. A clear pattern of co-infection was detected between mites and fleas and, to less extent, between mites and lice. Adult owls harbored fewer ectoparasites than nestlings, and adult females harbored more lice than males. Our results also show that mite and flea numbers were higher when more conspecifics cohabited the same burrow, while lice showed the opposite pattern. Rural individuals showed higher flea parasitism and lower mite parasitism than urban birds. Moreover, mite numbers were negatively correlated with aridity and host weight. Although the ectoparasitic load of burrowing owls appears to be influenced by individual age, sex, number of conspecifics per nest, and habitat characteristics, the pattern of co-infection found among ectoparasites could also be mediated by unexplored factors such as host immune response, which deserves further research

High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors

[EN] In spite of being widely used for in liquid biosensing applications, sensitivity improvement of conventional (5-20 MHz) quartz crystal microbalance (QCM) sensors remains an unsolved challenging task. With the help of a new electronic characterization approach based on phase change measurements at a constant fixed frequency, a highly sensitive and versatile high fundamental frequency (HFF) QCM immunosensor has successfully been developed and tested for its use in pesticide (carbaryl and thiabendazole) analysis. The analytical performance of several immunosensors was compared in competitive immunoassays taking carbaryl insecticide as the model analyte. The highest sensitivity was exhibited by the 100 MHz HFF-QCM carbaryl immunosensor. When results were compared with those reported for 9 MHz QCM, analytical parameters clearly showed an improvement of one order of magnitude for sensitivity (estimated as the I50 value) and two orders of magnitude for the limit of detection (LOD): 30 µg L-1 vs 0.66 µg L-1 I50 value and 11 µg L-1 vs 0.14 µg L-1 LOD, for 9 and 100 MHz, respectively. For the fungicide thiabendazole, I50 value was roughly the same as that previously reported for SPR under the same biochemical conditions, whereas LOD improved by a factor of 2. The analytical performance achieved by high frequency QCM immunosensors surpassed those of conventional QCM and SPR, closely approaching the most sensitive ELISAs. The developed 100 MHz QCM immunosensor strongly improves sensitivity in biosensing, and therefore can be considered as a very promising new analytical tool for in liquid applications where highly sensitive detection is required.We would like to acknowledge Federico Martin and Juan Antonio Buitrago for their excellent technical assistance. This work was supported by the Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (ERDF) (DETECTA IPT-2012-0154-300000 project).March Iborra, MDC.; García Narbón, JV.; Sánchez, Á.; Arnau Vives, A.; Jiménez Jiménez, Y.; García, P.; Manclus Ciscar, JJ.... (2015). High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors. Biosensors and Bioelectronics. (65):1-8. https://doi.org/10.1016/j.bios.2014.10.001S186

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses

New national and regional bryophyte records, 72

ABSTRACT: New record of Sphagnum palustre L. to Graciosa Island (Azores).info:eu-repo/semantics/publishedVersio

Plan piloto desarrollo de un programa de mentoría en el programa de doctorado “Formación en la Sociedad del Conocimiento” y creación de un espacio de trabajo colaborativo online

Memoria ID-027 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021