Innovative designs and applications of Janus micromotors with (photo)-catalytic and magnetic motion

El objetivo principal de esta Tesis Doctoral es el diseño y desarrollo de micromotores Janus biocompatibles y su aplicación en ámbitos relevantes de la salud y de la protección medioambiental. Los micromotores Janus son dispositivos en la microescala autopropulsados que tienen al menos dos regiones en su superficie con diferentes propiedades físicas y químicas, lo que les convierte en una clase distintiva de materiales que pueden combinar características ópticas, magnéticas y eléctricas en una sola entidad. Como la naturaleza del micromotor Janus -el dios romano de las dos caras- los objetivos de esta Tesis Doctoral presentan naturaleza dual y comprenden desarrollos de química fundamental y de química aplicada. En efecto, por una parte, el objetivo central aborda el diseño, síntesis y ensamblaje, así como la caracterización de micromotores Janus poliméricos propulsados por mecanismos (foto)-catalíticos y/o accionados por campos magnéticos. Por otra parte, el objetivo central implica la aplicación de los micromotores desarrollados para resolver desafíos sociales relevantes en los ámbitos químico-analítico, biomédico y ambiental. Partiendo de estas premisas, en la primera parte de la Tesis Doctoral, se sintetizaron micromotores Janus de policaprolactona propulsados químicamente integrando nanomateriales para el diseño de sensores móviles para la detección selectiva de endotoxinas bacterianas. De esta forma, el movimiento autónomo del micromotor mejora la mezcla de fluidos y la eficacia de las reacciones implicadas permitiendo detectar el analito en pocos minutos, incluso en muestras viscosas y medios donde la agitación no es posible. Además, esta autopropulsión es altamente compatible con su empleo en formatos ultra-miniaturizados para el desarrollo de futuros dispositivos portátiles en el marco de la tecnología point of care para aplicaciones clínicas y agroalimentarias. Con el fin de incrementar su biocompatibilidad para aplicaciones in vivo, en una segunda etapa de la Tesis Doctoral, se diseñaron micromotores Janus con propulsión autónoma utilizando luz visible para la eliminación de toxinas relevantes en procesos inflamatorios. El fenómeno autopropulsivo del micromotor y su capacidad de interacción con agentes tóxicos condujo a metodologías más rápidas y eficaces infiriéndose un futuro prometedor de estos micromotores para el tratamiento del shock séptico o intoxicación. En una tercera etapa, se sintetizaron micromotores propulsados por campos magnéticos. Estos micromotores utilizan una aproximación elegante de propulsión, exenta del empleo de combustibles químicos tóxicos como sucede en la propulsión catalítica y, en consecuencia, biocompatible. Asimismo, este mecanismo propulsivo permite controlar e incluso programar su trayectoria para aplicaciones que requieran de un guiado y de un control preciso de esta. De manera específica, estos micromotores han sido aplicados en esta Tesis Doctoral para la liberación controlada de fármacos en el tratamiento de cáncer pancreático y como elementos de remediación ambiental en la eliminación de agentes nerviosos en aguas contaminadas

Development and evaluation of novel biodegradable nanoparticles for vaccine delivery

The development and evaluation of a chitosan-dextran sulfate nanoparticulate vaccine delivery system, with incorporation of Immunoglobulin-A as an immunological adjuvant with M-cell targeting potential, are described in this thesis. This research project highlights the importance of nanoparticulate systems and novel adjuvants in the development of efficient and safe vaccines with an emphasis on defining a correlation between pharmaceutical formulation factors and in-vivo immunological responses

Nanomotors for Nucleic Acid, Proteins, Pollutants and Cells Detection

The development of nanomachines able to operate at the nanoscale, performing complex tasks such as drug delivery, precision surgery, or cell detection, constitutes one of the most important challenges in nanotechnology. The principles that rule the nanoscale are completely different from the ones which govern the macroscopic world and, therefore, the collaboration of scientists with expertise in different fields is required for the effective fabrication of these tiny machines. In this review, the most recent advances carried out in the synthesis and application of nanomachines for diagnosis applications will be presented in order to provide a picture of their potential in the detection of important biomolecules or pathogens in a selective and controlled manne

Enhancing photocatalytic degradation of the cyanotoxin microcystin-LR with the addition of sulfate-radical generating oxidants.

This study investigated the coupling of sulfate radical generating oxidants, (persulfate, PS and peroxymonosulfate, PMS) with TiO2 photocatalysis for the degradation of microcystin-LR (MC-LR). Treatment efficiency was evaluated by estimating the electrical energy per order (EEO). Oxidant addition at 10 mg/L reduced the energy requirements of the treatment by 60% and 12% for PMS and PS, respectively compared with conventional photocatalysis. Quenching studies indicated that both sulfate and hydroxyl radicals contributed towards the degradation of MC-LR for both oxidants, while Electron Paramagnetic Resonance (EPR) studies confirmed that the oxidants prolonged that lifetime of both radicals (concentration maxima shifted from 10 to 20min), allowing for bulk diffusion and enhancing cyanotoxin removal. Structural identification of transformation products (TPs) formed during all treatments, indicated that early stage degradation of MC-LR occurred mainly on the aromatic ring and conjugated carbon double bonds of the ADDA amino acid. In addition, simultaneous hydroxyl substitution of the aromatic ring and the conjugated double carbon bonds of ADDA (m/z= 1027.5) are reported for the first time. Oxidant addition also increased the rates of formation/degradation of TPs and affected the overall toxicity of the treated samples. The detoxification and degradation order of the treatments was UVA/TiO2/PMS > UVA/TiO2/PS>> UVA/TiO2

Microplastics effects in Scrobicularia plana

One of the most common plastics in the marine environment is polystyrene (PS) that can be broken down to micro sized particles. Marine organisms are vulnerable to the exposure to microplastics. This study assesses the effects of PS microplastics in tissues of the clam Scrobicularia plana. Clams were exposed to 1mgL-1(20μm) for 14days, followed by 7days of depuration. A qualitative analysis by infrared spectroscopy in diffuse reflectance mode period detected the presence of microplastics in clam tissues upon exposure, which were not eliminated after depuration. The effects of microplastics were assessed by a battery of biomarkers and results revealed that microplastics induce effects on antioxidant capacity, DNA damage, neurotoxicity and oxidative damage. S. plana is a significant target to assess the environmental risk of PS microplastics.info:eu-repo/semantics/publishedVersio

Mimicking tricks from nature with sensory organic-inorganic hybrid materials

Design strategies for (bio)chemical systems that are inspired by nature's accomplishments in system design and operation on various levels of complexity are increasingly gaining in importance. Within the broad field of biomimetic chemistry, this article highlights various attempts toward improved and sophisticated sensory materials that rely on the combination of supramolecular (bio)chemical recognition principles and nanoscopic solid structures. Examples range from more established concepts such as hybrid sensing ensembles with improved sensitivity and selectivity or for target analytes for which selectivity is hard to achieve by conventional methods, which were often inspired by protein binding pockets or ion channels in membranes, to very recent approaches relying on target-gated amplified signalling with functionalised mesoporous inorganic supports and the integration of native biological sensory species such as transmembrane proteins in spherically supported bilayer membranes. Besides obvious mimicry of recognition-based processes, selected approaches toward chemical transduction junctions utilizing artificially organized synapses, hybrid ensembles for improved antibody generation and uniquely colour changing systems are discussed. All of these strategies open up exciting new prospects for the development of sensing concepts and sensory devices at the interface of nanotechnology, smart materials and supramolecular (bio)chemistry. © 2011 The Royal Society of Chemistry.Martínez Mañez, R.; Sancenón Galarza, F.; Biyikal, M.; Hecht, M.; Rurack, K. (2011). Mimicking tricks from nature with sensory organic-inorganic hybrid materials. Journal of Materials Chemistry. 21(34):12588-12604. doi:10.1039/c1jm11210dS12588126042134Ma, M. (2007). Encoding Olfactory Signals via Multiple Chemosensory Systems. Critical Reviews in Biochemistry and Molecular Biology, 42(6), 463-480. doi:10.1080/10409230701693359Leinders-Zufall, T., Lane, A. P., Puche, A. C., Ma, W., Novotny, M. 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Biochemistry, 41(26), 8221-8228. doi:10.1021/bi0260839Lin, V. S.-Y., Lai, C.-Y., Huang, J., Song, S.-A., & Xu, S. (2001). Molecular Recognition Inside of Multifunctionalized Mesoporous Silicas:  Toward Selective Fluorescence Detection of Dopamine and Glucosamine. Journal of the American Chemical Society, 123(46), 11510-11511. doi:10.1021/ja016223mRadu, D. R., Lai, C.-Y., Wiench, J. W., Pruski, M., & Lin, V. S.-Y. (2004). Gatekeeping Layer Effect:  A Poly(lactic acid)-coated Mesoporous Silica Nanosphere-Based Fluorescence Probe for Detection of Amino-Containing Neurotransmitters. Journal of the American Chemical Society, 126(6), 1640-1641. doi:10.1021/ja038222vDescalzo, A. B., Rurack, K., Weisshoff, H., Martínez-Máñez, R., Marcos, M. D., Amorós, P., … Soto, J. (2005). Rational Design of a Chromo- and Fluorogenic Hybrid Chemosensor Material for the Detection of Long-Chain Carboxylates. Journal of the American Chemical Society, 127(1), 184-200. doi:10.1021/ja045683nComes, M., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Villaescusa, L. A., … Beltrán, D. (2004). Chromogenic Discrimination of Primary Aliphatic Amines in Water with Functionalized Mesoporous Silica. Advanced Materials, 16(20), 1783-1786. doi:10.1002/adma.200400143(s. f.). doi:10.1021/ol052298García-Acosta, B., Comes, M., Bricks, J. L., Kudinova, M. A., Kurdyukov, V. V., Tolmachev, A. I., … Amorós, P. (2006). Sensory hybrid host materials for the selective chromo-fluorogenic detection of biogenic amines. Chem. Commun., (21), 2239-2241. doi:10.1039/b602497aComes, M., Marcos, M. D., Martínez-Máñez, R., Millán, M. C., Ros-Lis, J. V., Sancenón, F., … Villaescusa, L. A. (2006). Anchoring Dyes into Multidimensional Large-Pore Zeolites: A Prospective Use as Chromogenic Sensing Materials. Chemistry - A European Journal, 12(8), 2162-2170. doi:10.1002/chem.200500932Comes, M., Rodríguez-López, G., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Beltrán, D. (2005). 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Journal of Materials Chemistry, 15(27-28), 2965. doi:10.1039/b501897hLee, S. J., Lee, J.-E., Seo, J., Jeong, I. Y., Lee, S. S., & Jung, J. H. (2007). Optical Sensor Based on Nanomaterial for the Selective Detection of Toxic Metal Ions. Advanced Functional Materials, 17(17), 3441-3446. doi:10.1002/adfm.200601202Palomares, E., Vilar, R., & Durrant, J. R. (2004). Heterogeneous colorimetric sensor for mercuric saltsElectronic supplementary information (ESI) available: Materials and methods. See http://www.rsc.org/suppdata/cc/b3/b314138a/. Chemical Communications, (4), 362. doi:10.1039/b314138aWang, Y., Li, B., Zhang, L., Liu, L., Zuo, Q., & Li, P. (2010). A highly selective regenerable optical sensor for detection of mercury(ii) ion in water using organic–inorganic hybrid nanomaterials containing pyrene. New Journal of Chemistry, 34(9), 1946. doi:10.1039/c0nj00039fLi, L.-L., Sun, H., Fang, C.-J., Xu, J., Jin, J.-Y., & Yan, C.-H. (2007). 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The Journal of Physical Chemistry C, 112(13), 5014-5022. doi:10.1021/jp7099948Gao, L., Wang, Y., Wang, J., Huang, L., Shi, L., Fan, X., … Li, Z. (2006). A Novel ZnII-Sensitive Fluorescent Chemosensor Assembled within Aminopropyl-Functionalized Mesoporous SBA-15. Inorganic Chemistry, 45(17), 6844-6850. doi:10.1021/ic0516562Balaji, T., Sasidharan, M., & Matsunaga, H. (2005). Naked eye detection of cadmium using inorganic–organic hybrid mesoporous material. Analytical and Bioanalytical Chemistry, 384(2), 488-494. doi:10.1007/s00216-005-0187-2Balaji, T., El-Safty, S. A., Matsunaga, H., Hanaoka, T., & Mizukami, F. (2006). Optical Sensors Based on Nanostructured Cage Materials for the Detection of Toxic Metal Ions. Angewandte Chemie International Edition, 45(43), 7202-7208. doi:10.1002/anie.200602453El-Safty, S. A., Ismail, A. A., Matsunaga, H., & Mizukami, F. (2007). Optical Nanosensor Design with Uniform Pore Geometry and Large Particle Morphology. Chemistry - A European Journal, 13(33), 9245-9255. doi:10.1002/chem.200700499El-Safty, S. A., Ismail, A. A., Matsunaga, H., Hanaoka, T., & Mizukami, F. (2008). Optical Nanoscale Pool-on-Surface Design for Control Sensing Recognition of Multiple Cations. Advanced Functional Materials, 18(10), 1485-1500. doi:10.1002/adfm.200701059Ros-Lis, J. V., Casasús, R., Comes, M., Coll, C., Marcos, M. D., Martínez-Máñez, R., … Rurack, K. (2008). A Mesoporous 3D Hybrid Material with Dual Functionality for Hg2+Detection and Adsorption. Chemistry - A European Journal, 14(27), 8267-8278. doi:10.1002/chem.200800632Lee, S. J., Bae, D. R., Han, W. S., Lee, S. S., & Jung, J. H. (2008). Different Morphological Organic–Inorganic Hybrid Nanomaterials as Fluorescent Chemosensors and Adsorbents for CuII Ions. European Journal of Inorganic Chemistry, 2008(10), 1559-1564. doi:10.1002/ejic.200701073Lee, H. Y., Bae, D. R., Park, J. C., Song, H., Han, W. S., & Jung, J. H. (2009). A Selective Fluoroionophore Based on BODIPY-functionalized Magnetic Silica Nanoparticles: Removal of Pb2+ from Human Blood. Angewandte Chemie International Edition, 48(7), 1239-1243. doi:10.1002/anie.200804714Haupt, K., & Mosbach, K. (2000). Molecularly Imprinted Polymers and Their Use in Biomimetic Sensors. Chemical Reviews, 100(7), 2495-2504. doi:10.1021/cr990099wWulff, G. (2002). Enzyme-like Catalysis by Molecularly Imprinted Polymers. Chemical Reviews, 102(1), 1-28. doi:10.1021/cr980039aSellergren, B. (1997). Noncovalent molecular imprinting: antibody-like molecular recognition in polymeric network materials. TrAC Trends in Analytical Chemistry, 16(6), 310-320. doi:10.1016/s0165-9936(97)00027-7D�az-Garc�a, M. E., & La�n�o, R. B. (2004). Molecular Imprinting in Sol-Gel Materials: Recent Developments and Applications. Microchimica Acta, 149(1-2), 19-36. doi:10.1007/s00604-004-0274-7Bossi, A., Bonini, F., Turner, A. P. F., & Piletsky, S. A. (2007). 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A Novel Approach to Formulation of Anticancer Drugs in Nanoparticles.

Many anticancer drugs, due to their hydrophilicity, have poor drug loading in nanoparticles. Charge-charge interactions may be effective for improving loading where charges in nanoparticles attract oppositely charged drug molecules. A new strategy, incorporation of charged hydrophobic excipients into nanoparticles followed by drug loading via incubation, may effectively increase drug loading. First, hydrophobic alkyl sulfates were tested for improved loading of a model hydrophilic drug, doxorubicin hydrochloride (doxHCl). Ion pairing between alkyl sulfates and doxHCl yielded hydrophobic complexes and indicated favorable incorporation into hydrophobic nanoparticle cores. However, encapsulation into nanoparticles failed due to poor complex solubility in organic solvents. A more hydrophobic series of borate-based anionic excipients was then studied. Solubility studies found ethyl acetate to be a suitable organic solvent for dissolving borate-based excipients at high concentrations. One of the excipients, potassium tetrakis(4-chlorophenyl) borate (KTpClPB), was the best as it had characteristics suitable for extraction of doxHCl into a hydrophobic phase. A new incubation loading strategy was utilized for drug uptake into nanoparticles. Optimization of this process found maximizing free acid number of polymers, amount of KTpClPB used, and drug:nanoparticle ratio increased drug loading. Increasing incubation temperature increased polymer strand rearrangements and promoted drug uptake. PEGylation of nanoparticles reduced nanoparticle aggregation to promote drug uptake. Using the optimized incubation loading procedure, another model drug, vinblastine sulfate, also achieved high drug loading, demonstrating that this procedure may be more broadly applicable. Comparison of incubation loading with traditional drug loading procedures (O/W or W/O/W emulsions), found traditional drug loading produced half the loading relative to incubation loading due to limited drug extraction into organic phase of O/W emulsions and limited inner aqueous phase volume of W/O/W emulsions. In vitro drug release profiles were similar for all nanoparticles, and the presence of KTpClPB, despite charge attractions, failed to slow drug release.Ph.D.Pharmaceutical SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61624/1/gux_1.pd

Advances in Microfluidic Technologies for Energy and Environmental Applications

Microfluidics have aroused a new surge of interest in recent years in environmental and energy areas, and inspired novel applications to tackle the worldwide challenges for sustainable development. This book aims to present readers with a valuable compendium of significant advances in applying the multidisciplinary microfluidic technologies to address energy and environmental problems in a plethora of areas such as environmental monitoring and detection, new nanofluid application in traditional mechanical manufacturing processes, development of novel biosensors, and thermal management. This book will provide a new perspective to the understanding of the ever-growing importance of microfluidics