Advances in colloidal manipulation and transport via hydrodynamic interactions

In this review article, we highlight many recent advances in the field of micromanipulation of colloidal particles using hydrodynamic interactions (HIs), namely solvent mediated long-range interactions. At the micrsocale, the hydrodynamic laws are time reversible and the flow becomes laminar, features that allow precise manipulation and control of colloidal matter. We focus on different strategies where externally operated microstructures generate local flow fields that induce the advection and motion of the surrounding components. In addition, we review cases where the induced flow gives rise to hydrodynamic bound states that may synchronize during the process, a phenomenon essential in different systems such as those that exhibit self-assembly and swarming

Enzyme Powered Nanomotors Towards Biomedical Applications

[eng] The advancements in nanotechnology enabled the development of new diagnostic tools and drug delivery systems based on nanosystems, which offer unique features such as large surface area to volume ratio, cargo loading capabilities, increased circulation times, as well as versatility and multifunctionality. Despite this, the majority of nanomedicines do not translate into clinics, in part due to the biological barriers present in the body. Synthetic nano- and micromotors could be an alternative tool in nanomedicine, as the continuous propulsion force and potential to modulate the medium may aid tissue penetration and drug diffusion across biological barriers. Enzyme-powered motors are especially interesting for biomedical applications, owing to their biocompatibility and use of bioavailable substrates as fuel for propulsion. This thesis aims at exploring the potential applications of urease-powered nanomotors in nanomedicine. In the first work, we evaluated these motors as drug delivery systems. We found that active urease- powered nanomotors showed active motion in phosphate buffer solutions, and enhanced in vitro drug release profiles in comparison to passive nanoparticles. In addition, we observed that the motors were more efficient in delivering drug to cancer cells and caused higher toxicity levels, due to the combination of boosted drug release and local increase of pH produced by urea breakdown into ammonia and carbon dioxide. One of the major goals in nanomedicine is to achieve localized drug action, thus reducing side-effects. A commonly strategy to attain this is the use moieties to target specific diseases. In our second work, we assessed the ability of urease-powered nanomotors to improve the targeting and penetration of spheroids, using an antibody with therapeutic potential. We showed that the combination of active propulsion with targeting led to a significant increase in spheroid penetration, and that this effect caused a decrease in cell proliferation due to the antibody’s therapeutic action. Considering that high concentrations of nanomedicines are required to achieve therapeutic efficiency; in the third work we investigated the collective behavior of urease-powered nanomotors. Apart from optical microscopy, we evaluated the tracked the swarming behavior of the nanomotors using positron emission tomography, which is a technique widely used in clinics, due to its noninvasiveness and ability to provide quantitative information. We showed that the nanomotors were able to overcome hurdles while swimming in confined geometries. We observed that the nanomotors swarming behavior led to enhanced fluid convection and mixing both in vitro, and in vivo within mice’s bladders. Aiming at conferring protecting abilities to the enzyme-powered nanomotors, in the fourth work, we investigated the use of liposomes as chassis for nanomotors, encapsulating urease within their inner compartment. We demonstrated that the lipidic bilayer provides the enzymatic engines with protection from harsh acidic environments, and that the motility of liposome-based motors can be activated with bile salts. Altogether, these results demonstrate the potential of enzyme-powered nanomotors as nanomedicine tools, with versatile chassis, as well as capability to enhance drug delivery and tumor penetration. Moreover, their collective dynamics in vivo, tracked using medical imaging techniques, represent a step-forward in the journey towards clinical translation.[spa] Recientes avances en nanotecnología han permitido el desarrollo de nuevas herramientas para el diagnóstico de enfermedades y el transporte dirigido de fármacos, ofreciendo propiedades únicas como encapsulación de fármacos, el control sobre la biodistribución de estos, versatilidad y multifuncionalidad. A pesar de estos avances, la mayoría de nanomedicinas no consiguen llegar a aplicaciones médicas reales, lo cual es en parte debido a la presencia de barreras biológicas en el organismo que limitan su transporte hacia los tejidos de interés. En este sentido, el desarrollo de nuevos micro- y nanomotores sintéticos, capaces de autopropulsarse y causar cambios locales en el ambiente, podrían ofrecer una alternativa para la nanomedicina, promoviendo una mayor penetración en tejidos de interés y un mejor transporte de fármacos a través de las barreras biológicas. En concreto, los nanomotores enzimáticos poseen un alto potencial para aplicaciones biomédicas gracias a su biocompatibilidad y a la posibilidad de usar sustancias presentes en el organismo como combustible. Los trabajos presentados en esta tesis exploran el potenical de nanomotores, autopropulsados mediante la enzima ureasa, para aplicaciones biomédicas, y investigan su uso como vehículos para transporte de fármacos, su capacidad para mejorar penetración de tejidos diana, su versatilidad y movimiento colectivo. En conjunto, los resultados presentados en esta tesis doctoral demuestran el potencial del uso de nanomotores autopropulsados mediante enzimas como herramientas biomédicas, ofreciendo versatilidad en su diseño y una alta capacidad para promover el transporte de fármacos y la penetración en tumores. Por último, su movimiento colectivo observado in vivo mediante técnicas de imagen médicas representan un significativo avance en el viaje hacia su aplicación en medicina

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

Micro Propulsion in Liquid by Oscillating Bubbles

A number of attempts have been made to fabricate microswimmers that possibly navigate in vivo including the artificial magnetic bacteria flagella, chemical microswimmers and natural organism based microswimmers. This paper presents another propelling mechanism in micron scale that works by oscillating microbubbles in acoustic field. First of all, the propulsion mechanism is proven by two-dimensional computational fluid dynamics (CFD) simulations. Then, the microswimmer device is made on a parylene structure by photolithography. The underwater propulsion in one-dimensional is demonstrated and the propulsion mechanism is also confirmed by experiments. The relation of the propulsion speed/bubble oscillation amplitude and the input acoustic signal is measured. It is shown that the propulsion will happen when the bubble oscillation amplitude (or Reynolds number) gets large enough which is close to the system acoustic resonance. Around this resonance frequency (about 11 kHz), the measured propulsion speed is up to 45 mm/s and payload-carrying ability is realized. The one-directional rotation acoustic turbo is also made with a speed of about 75 rpm. This acoustic frequency dependence also becomes the foundation for two-dimensional propulsion. Then, the bi-directional motion and two-dimensional steering motion are realized by microbubbles with different lengths based on their different acoustic resonances. First of all, the frequency behavior for long (about 760 μm average length) and short (about 300 μm average length) bubbles at about 6 kHz and 11 kHz are measured, including oscillation amplitude and generated microstreaming. By adjusting input acoustic frequency, specific bubbles could be activated selectively. Then, when the different microbubbles are arranged into opposite directions, the bi-directional propulsion can be realized, including back/forth motion and clockwise/counter-clockwise rotation. The bi-directional motion mechanism is also confirmed by three-dimensional CFD simulations and the net force is calculated. The concept is further developed into two-dimensional propulsion by arranging long and short bubbles into orthogonal directions on the same device. By switching the input acoustic frequency, the controlled steering propulsion is illustrated on a two-dimensional plane. Carrying of objects in a T-junction microchannel is shown as well. The last part of this thesis is focused on developing the microswimmer into a biodegradable device, including long- and short-tem. The long-term biodegradable device is fabricated by polycaprolactone (PCL) by a simple dipping method, and propulsion in a minitube is shown. The short-term biodegradable device is fabricated by rolling up magnesium film based on building stress mismatch mechanically with help of a stretcher. The method could also be applied to aluminium and parylene film rollups. At last, the propulsion and biodegradable abilities of magnesium microtube are demonstrated

Micromotors for Environmental Applications

[eng] Scarce supply of clean water and rising water pollution are key global challenges for water sustainability. Much of the wastewater generated by human agricultural and industrial activity is left untreated. Nanotechnological materials and systems have emerged as new tools for improving the efficiency of water treatment. Among those, self-propelled micromotors have shown several advantageous characteristics. Micromotors are autonomously propelled systems which either use chemical energy present in their environment or are propelled via external force fields. Diverse designs, materials composition and mechanisms of propulsion are reported for micromotors found in the literature. Among them, bubble-propelled micromotors, which move due to the generation and release of gas bubbles from their surface, are the main type of motors used for water remediation applications. In addition to the motion in fluids, the bubbles generated by the motors, also contribute with additional mixing of the fluid and enhance the mass transfer between active material and pollutant at the microscale. Additionally, the structure of micromotors can be modified to target a wide variety of pollutants, almost on demand. The micromotors that we synthesized during the research work for this thesis can remove organic and heavy metal pollutants, as well as exhibit bactericidal activity. We studied Iron/Platinum (Fe/Pt) micromotors for their reusability, effect of sizes, swimming behaviors and catalytic properties. These micromotors were fabricated by spontaneous roll-up of iron and platinum nanomembranes, deposited on the pre-fabricated patterns of a photoresist substrate. The iron layer present as the outer surface of these micromotors can degrade organic pollutants via Fenton-like reaction and the inner platinum layer acts as the engine decomposing hydrogen peroxide to oxygen for bubble propulsion. We observed that Fe/Pt micromotors can swim continuously for hours, and can be stored for weeks before reuse, without sacrificing much of their activity. The results suggested that Fe/Pt micromotors act as a heterogeneous catalyst due to in situ generated iron oxide species on the surface, without leaching high concentration of iron in the media. We developed graphene oxide-based micromotors (GOx-micromotors) for heavy metal removal, consisting of nanosized multilayers of graphene oxide, nickel, and platinum. These micromotors can capture, transfer, and remove heavy metals (i.e. lead) from contaminated water. GOx-micromotors are synthesized by electrodepositions of electro-reducible graphene oxide, nickel and platinum layers in the polycarbonate porous templates. The outer layer of graphene oxide captures lead on their surface, and the inner layer of platinum provides self-propulsion in hydrogen peroxide, while the middle layer of nickel enables external magnetic control of the micromotors. We observed that the mobile GOx-micromotors can remove lead 10 times more efficiently than non-motile GOx-micromotors, cleaning water from 1000 ppb down to below 50 ppb. We have demonstrated control of their motion and directionality in a proof of concept microfluidic system. Silver nanoparticles (AgNPs) decorated Magnesium Janus micromotors were designed for disinfection and remove of Escherichia coli (E. coli) bacteria from contaminated water. Magnesium present in the micromotors functions as both, the template for the spherical shape and propulsion source by producing hydrogen bubbles while in contact with water. The inner layer of iron provides functionality for the magnetic remote guidance, and an outer AgNP coated gold layer facilitates adhesion of bacteria and gives bactericidal properties to the micromotors. We observed that the AgNPs-coated Au cap of the micromotors shows dual capabilities, capturing bacteria and killing them. In our efforts to develop multifunctional micromotors and scalable synthesis methods, we developed two types of micromotors. (i) Mesoporous silica-based micromotors with manganese dioxide (MnO2) layer on the inner surface and coated with γ-Fe2O3 nanoparticles (FeSiMnOx micromotors). These micromotors can remove both organic and heavy metal pollutants, and they are synthesized using only template-assisted chemical methods. (ii) Cobalt ferrite micromotors (CFO micromotors) synthesized by template-free chemical synthesis approach. They are made up of aggregated cobalt ferrite nanoparticles, which act as the catalyst for propulsion and for Fenton-like reactions. We qualitatively measured the generation of hydroxyl radicals by CFO micromotors and studied the effect of surfactants on the degradation efficiency of CFO micromotors. We hope that such approach of synthesizing micromotors via relatively facile methods will push the use of micromotors towards commercially practical solutions for water treatment. Overall, our results show that the multifunctional self-propelled micromotors have potential to become an effective tool for water remediation in the near future.[spa] El escaso suministro de agua limpia y el aumento de la contaminación del agua son desafíos globales clave para la sostenibilidad del agua, sobre todo teniendo en cuenta que gran parte del agua residual generada por la actividad agrícola e industrial humana no se trata. Los materiales y sistemas nanotecnológicos han surgido como nuevas herramientas para mejorar la eficiencia del tratamiento de aguas. Entre ellos, los micromotores autopropulsados han mostrado varias características ventajosas. Los micromotores son sistemas de propulsión autónoma que utilizan energía química presente en su entorno o pueden también ser propulsadas a través de campos de fuerzas aplicadas externamente. Varios diseños, composición de materiales y mecanismos de propulsión se han sido reportados en el campo de los micromotores. Entre ellos, principalmente los micromotores propulsados por burbujas, los cuales se mueven debido a la generación y liberación de burbujas de gas de su superficie, se utilizan como una herramienta para aplicaciones de remediación de aguas. Esto se debe a la eficacia añadida de la transferencia de masa a la microescala, que se origina a partir de su movimiento y el movimiento de las burbujas liberadas. Además, la estructura de los micromotores se puede modificar para dirigirse a una amplia variedad de contaminantes, según los requerimientos. Los micromotores que sintetizamos durante el trabajo de investigación para esta tesis pueden eliminar contaminantes orgánicos y metales pesados, así como exhibir actividad anti bactericida. Estudiamos micromotores de hierro / platino (Fe / Pt) por su reutilización, efecto de tamaños, su comportamiento durante su movimiento y propiedades catalíticas. Estos micromotores se fabricaron mediante enrollamiento espontáneo de nanomembranas de hierro y platino, depositadas en los patrones prefabricados definidos en una capa sacrificial fotorresistente. La capa de hierro presente como superficie externa de estos micromotores puede degradar los contaminantes orgánicos a través de la reacción tipo Fenton y la capa interna de platino actúa como el motor, siendo el catalizador que descompone el peróxido de hidrógeno en oxígeno para generar una propulsión por burbujas. Observamos que los micromotores Fe / Pt pueden nadar continuamente durante horas y pueden almacenarse durante semanas antes de volver a ser usados, sin que esto repercuta de manera significativa en su actividad. Los resultados de nuestros experimentos sobre el análisis de superficie de micromotores, estudio de nanoindentación y liberación de hierro sugirieron que los micromotores Fe / Pt actúan como un catalizador heterogéneo debido a las especies de óxido de hierro generadas in situ en la superficie, sin lixiviación de alta concentración de hierro en los medios. Desarrollamos micromotores basados en óxido de grafeno (micromotores GOx) para la eliminación de metales pesados que consisten en multicapas nanométricas de óxido de grafeno, níquel y platino. Estos micromotores pueden capturar, transferir y eliminar metales pesados (es decir, plomo) del agua contaminada. Los micromotores GOx se sintetizan mediante electrodeposiciones de capas de óxido de grafeno, níquel y platino, los cuales son electroreducidos en la parte interior de membranas de policarbonato porosas. La capa externa de óxido de grafeno captura el plomo en su superficie, y la capa interna de platino proporciona autopropulsión en presencia de peróxido de hidrógeno, mientras que la capa intermedia de níquel permite el control magnético externo de los micromotores. Observamos que los micromotores móviles GOx pueden eliminar el plomo hasta 10 veces más que los micromotores GOx no móviles (Figura 1B), limpiando el plomo en agua de 1000 ppb a menos de 50 ppb en menos de 60 min. Hemos demostrado el control de su movimiento y direccionalidad en un sistema microfluídico como prueba de concepto. Diseñamos también micromotores tipo Janus decorados con nanopartículas de plata (AgNP) para la desinfección y eliminación de la bacteria Escherichia coli (E. coli) en agua contaminada. Los micromotores Janus se sintetizaron recubriendo un lado de una micro-partícula de magnesio con capas de hierro y oro, las cuales posteriormente se funcionalizaron con AgNP. El magnesio presente en los micromotores funciona no sólo como estructura principal para conseguir una forma esférica, sino también como fuente de propulsión mediante la producción de burbujas de hidrógeno al entrar en contacto con el agua. La capa interna de hierro proporciona la funcionalidad requerida para el posterior control magnético externo, mientras que la capa de oro externa decorada con AgNPs promueve la adhesión de bacterias y dota de propiedades bactericidas a los micromotores. En nuestro esfuerzo por desarrollar micromotores multifuncionales y métodos de síntesis escalables, desarrollamos dos tipos de micromotores. (i) Micromotores mesoporosos basados en sílice con una capa de dióxido de manganeso (MnO2) en la superficie interna y recubiertos con nanopartículas γ-Fe2O3 (micromotores FeSiMnOx). Estos micromotores pueden eliminar contaminantes orgánicos y metales pesados, y se sintetizan utilizando solo métodos químicos asistidos por un molde (por ejemplo, una membrana porosa). (ii) Los micromotores de ferrita de cobalto (micromotores CFO) fueron sintetizados sin necesidad de utilizar ningún molde. Están formados por nanopartículas de ferrita de cobalto agregadas, que actúan como catalizadores para la propulsión y para reacciones tipo Fenton. Medimos cualitativamente la generación de radicales hidroxilos por micromotores CFO y estudiamos el efecto de los tensioactivos sobre la eficiencia de degradación de los micromotores CFO. Esperamos que la síntesis de micromotores a través de métodos relativamente fáciles empuje la implementación de micromotores en soluciones comercialmente prácticas para el tratamiento del agua. En general, nuestros resultados muestran que los micromotores autopropulsados multifuncionales tienen el potencial de convertirse en una herramienta efectiva para la limpieza de aguas en el futuro

Motility study of shaped active colloids: Bacteria and Janus Particles

Incomin

Optical trapping in micro- and nanoconfinement systems: Role of thermo-fluid dynamics and applications

In this mini-review, recent advances on the role of a focused laser in micro- and nanofluidic systems is widely introduced with special interest in thermo-fluid dynamical aspects and their importance in optical manipulation. As a brief introduction to microfluidic systems, we describe the advantages and challenges of the use of micro- and nanoscale confinement in optical trapping, as well as standard fabrication techniques for micro- and nanofluidic systems. From thermo-fluid dynamical viewpoints, various phenomena that accompany a laser irradiation to fluidic devices, are explained in detail. These phenomena can affect the optical trapping of target materials significantly, and are classified into two categories: one that induces the fluid flow around the target and another that directly acts on it as an external force. These classes are reviewed by shedding light on some recent cutting-edge researches for optical manipulation. Some applications using thermo-fluid dynamics in microfluidic systems for the measurement of optical forces and for the separation, measurement, and detection of target materials are also introduced

Microswimmers with heat delivery capacity for 3D cell spheroid penetration

Micro- and nanoswimmers are a fast emerging concept that changes how colloidal and biological systems interact. They can support drug delivery vehicles, assist in crossing biological barriers, or improve diagnostics. We report microswimmers that employ collagen, a major extracellular matrix (ECM) constituent, as fuel and that have the ability to deliver heat via incorporated magnetic nanoparticles when exposed to an alternating magnetic field (AMF). Their assembly and heating properties are outlined followed by the assessment of their calcium-triggered mobility in aqueous solution and collagen gels. It is illustrated that the swimmers in collagen gel in the presence of a steep calcium gradient exhibit fast and directed mobility. The experimental data are supported with theoretical considerations. Finally, the successful penetration of the swimmers into 3D cell spheroids is shown, and upon exposure to an AMF, the cell viability is impaired due to the locally delivered heat. This report illustrates an opportunity to employ swimmers to enhance tissue penetration for cargo delivery via controlled interaction with the ECM.Xunta de Galicia | Ref. ED431C 2016-034Ministerio de Economía y Competitividad | Ref. CTM2014-58481-RXunta de Galicia | Ref. 2017 ED481AUniversidade de Vig

Nanoparticles in polyelectrolyte multilayer layer-by-layer (LbL) films and capsules : key enabling components of hybrid coatings

Originally regarded as auxiliary additives, nanoparticles have become important constituents of polyelectrolyte multilayers. They represent the key components to enhance mechanical properties, enable activation by laser light or ultrasound, construct anisotropic and multicompartment structures, and facilitate the development of novel sensors and movable particles. Here, we discuss an increasingly important role of inorganic nanoparticles in the layer-by-layer assembly—effectively leading to the construction of the so-called hybrid coatings. The principles of assembly are discussed together with the properties of nanoparticles and layer-by-layer polymeric assembly essential in building hybrid coatings. Applications and emerging trends in development of such novel materials are also identified