79 research outputs found

    Advanced medical micro-robotics for early diagnosis and therapeutic interventions

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    Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome

    Analysis, Design and Fabrication of Micromixers, Volume II

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    Micromixers are an important component in micrototal analysis systems and lab-on-a-chip platforms which are widely used for sample preparation and analysis, drug delivery, and biological and chemical synthesis. The Special Issue "Analysis, Design and Fabrication of Micromixers II" published in Micromachines covers new mechanisms, numerical and/or experimental mixing analysis, design, and fabrication of various micromixers. This reprint includes an editorial, two review papers, and eleven research papers reporting on five active and six passive micromixers. Three of the active micromixers have electrokinetic driving force, but the other two are activated by mechanical mechanism and acoustic streaming. Three studies employs non-Newtonian working fluids, one of which deals with nano-non-Newtonian fluids. Most of the cases investigated micromixer design

    Robot-Assisted Full Automation Interface: Touch-Response On Zebrafish Larvae

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    Self-assembled artificial cilia actuator

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    Department of Mechanical EngineeringSlender hair-like cilia are observed in many living organisms. Cilia carry out important roles, such as locomotion, fluid control, fluid diffusion, and cleaning, owing to their high aspect ratio structure. Inspired by cilia in nature, artificial cilia actuators are being extensively developed. An artificial cilia actuator can generate shape morphing and actuation under external stimuli, such as pneumatic, electric-field, light, thermal, and chemical stimuli as well as a magnetic field. Pneumatic cilia actuators have a large driving force compared to their weight and are easy to manufacture. However, they cannot be miniaturized to a microscale, like cilia in nature, because additional components such as pumps and cables are essential. Electric cilia can be manufactured on a microscale and can actuate dynamicallyhowever, their applications are limited owing to their high voltage requirements. Light, chemical, and thermal stimuli-based cilia actuators can also be miniaturized on a microscale, but they have slow response times and do not easily generate the desired actuation. On the other hand, magnetic actuators can be miniaturized, controlled precisely, are non-invasive, and can be driven immediately. Owing to these advantages, cilia actuators based on magnetic fields have been intensively investigated. Magnetic cilia actuators are mainly constructed using a top-down approach. In this approach, a template mold with a lithographically defined hole array is replicated with a magnetic-particle mixture solution, which enables the reliable fabrication of magnetic cilia with controlled geometry. However, with this technique, synthetic cilia with nanoscopic diameters that are nearly the size of biological cilia are difficult to access owing to the limited pattern resolution of the lithographically prepared template and high viscosity of the composite solution. In addition, the aspect ratio of cilia is limited because the cilia may structurally collapse during a demolding step of the molding process. The self-assembly approach has emerged as a solution to the limitations of the top-down approach. This approach fabricates a desired structure by manipulating a driving force that moves particles, and it has strong potential for constructing a cilia array with a nanoscale size and high aspect ratio structure. The Langmuir???Blodgett conventional self-assembly technique can precisely control particles. However, this technique typically produces close-packed two-dimensional monolayer or three-dimensional lattice structures. Recently, spray-based and DNA-based self-assembly techniques were conducted to construct a vertical structure. However, spray-based self-assembly has random spatial distributions without controllability of the array geometry. DNA-based self-assembly has a complex processtherefore, obtaining a high aspect ratio is challenging. We propose a programmable self-assembly strategy that can direct magnetic particles into a highly ordered responsive artificial cilia actuator. The resulting cilia display several structural features, such as diameters of single-particle resolution, controllable diameters and lengths spanning from nanometers to micrometers, and accurate positioning. The proposed strategy is based on the vapor state, which minimizes intermolecular interaction, and precise magnetic-field control using a Ni island. The self-assembled artificial cilia can maintain their structural integrity through interparticle interactions. Interestingly, the cilia can exhibit a field-responsive actuation motion through ???rolling and sliding??? between assembled particles instead of bending the entire ciliary beam. We demonstrate that oleic acid used to coat the particles acts as a lubricating bearing and enables the rolling/sliding-based actuation of the cilia. We further demonstrate that both magnetic nanocilia and microcilia can dynamically and immediately actuate in response to modulated magnetic fields while providing different stroke ranges and actuation torques.ope

    Biohybrid robotics: From the nanoscale to the macroscale

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    Biohybrid robotics is a field in which biological entities are combined with artificial materials in order to obtain improved performance or features that are difficult to mimic with hand-made materials. Three main level of integration can be envisioned depending on the complexity of the biological entity, ranging from the nanoscale to the macroscale. At the nanoscale, enzymes that catalyze biocompatible reactions can be used as power sources for self-propelled nanoparticles of different geometries and compositions, obtaining rather interesting active matter systems that acquire importance in the biomedical field as drug delivery systems. At the microscale, single enzymes are substituted by complete cells, such as bacteria or spermatozoa, whose self-propelling capabilities can be used to transport cargo and can also be used as drug delivery systems, for in vitro fertilization practices or for biofilm removal. Finally, at the macroscale, the combinations of millions of cells forming tissues can be used to power biorobotic devices or bioactuators by using muscle cells. Both cardiac and skeletal muscle tissue have been part of remarkable examples of untethered biorobots that can crawl or swim due to the contractions of the tissue and current developments aim at the integration of several types of tissue to obtain more realistic biomimetic devices, which could lead to the next generation of hybrid robotics. Tethered bioactuators, however, result in excellent candidates for tissue models for drug screening purposes or the study of muscle myopathies due to their three-dimensional architecture

    Implementación de plataformas biosensoras ópticas basadas en nuevos elementos de reconocimiento selectivo para la monitorización de inmunosupresores en muestras sanguíneas

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    Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 14-07-2022Cada año aumenta la demanda de trasplantes de órganos en todo el mundo, y según los datos del Observatorio Mundial de Donación y Trasplante y de la Organización Mundial de la Salud, en 2019 se realizaron más de 153,800 intervenciones en 84 países. El éxito del trasplante y la correcta recuperación del paciente dependen, en gran parte, de que se controlen en el paciente los niveles adecuados de medicamentos inmunosupresores (ISDs) tras el trasplante, los cuales presentan ventanas terapéuticas estrechas y grandes variaciones de absorción inter e intraindividuo (dando origen aniveles impredecibles en la sangre). Por ello, uno de los objetivos fundamentales de las autoridades de la Salud Pública es la monitorización farmacoterapéutica de estos medicamentos, para asegurar la máxima respuesta terapéutica con los mínimos efectos adversos. Actualmente, en los laboratorios clínicos se emplea mayoritariamente la cromatografía líquida acoplada a diferentes detectores (ej. matriz de diodos, fluorescencia o espectrometría de masas) para la determinación de ISDs. Si bien todas estas técnicas proporcionan métodos sensibles y reproducibles, requieren personal debidamente entrenado, en algunos casos su coste es elevado y, en ocasiones, se requieren etapas adicionales de extracción y derivatización, aumentando los tiempos de análisis y la irreproducibilidad del método. Además, estos métodos no son adecuados para la monitorización semicontinua en dispositivos de análisis in situ (POC, del inglés point-of care)o para el cribado de alto rendimiento...The demand for organ transplantation increases worldwide every year and, according to the Global Observatory on Donation and Transplantation and the World Health Organization, more than 153,800 transplants were performed in 84 countries in 2019. The success of transplantation and correct recovery of the patient depends, to a large extent, on the control of adequate levels of immunosuppressive drugs (ISDs) in blood, as they present narrow therapeutic windows and large inter- and intra-individual absorption variations (that may result in unpredictable levels). Therefore, one of the main objectives of Public Health authorities is to ensure the adequate pharmacotherapeutic monitoring of immunosuppressants in organ recipients to ensure a maximum therapeutic response with the minimum adverse effects. Currently, liquid chromatography coupled to different detectors (e.g. diode array, fluorescence or mass spectrometry) is widely applied for the control of ISDs in clinical laboratories. Although all these techniques allow the development of sensitive and reproducible analytical methods, they require properly trained personnel and, in most cases, complex sample pretreatment steps that increase irreproducibility, the analysis time and the cost per assay. Furthermore, these methods are not suitable for semicontinuous monitoring in point-of-care (POC) devices or for high-throughput screening...Fac. de Ciencias QuímicasTRUEunpu

    Bacterial Biohybrid Microswimmers

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    Over millions of years, Nature has optimized the motion of biological systems at the micro and nanoscales. Motor proteins to motile single cells have managed to overcome Brownian motion and solve several challenges that arise at low Reynolds numbers. In this review, we will briefly describe naturally motile systems and their strategies to move, starting with a general introduction that surveys a broad range of developments, followed by an overview about the physical laws and parameters that govern and limit motion at the microscale. We characterize some of the classes of biological microswimmers that have arisen in the course of evolution, as well as the hybrid structures that have been constructed based on these, ranging from Montemagno's ATPase motor to the SpermBot. Thereafter, we maintain our focus on bacteria and their biohybrids. We introduce the inherent properties of bacteria as a natural microswimmer and explain the different principles bacteria use for their motion. We then elucidate different strategies that have been employed for the coupling of a variety of artificial microobjects to the bacterial surface, and evaluate the different effects the coupled objects have on the motion of the 'biohybrid.' Concluding, we give a short overview and a realistic evaluation of proposed applications in the field

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

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    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

    Transport and Microrheology of Active Colloids

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    Active colloids are micron-sized particles that self-propel through viscous fluids by converting energy extracted from their environment into mechanical motion. The origin or mechanism of their locomotion can be either biological or synthetic ranging from motile bacteria to artificial phoretic particles. Owing to their ability to self-propel, active colloids are out of thermodynamic equilibrium and exhibit interesting macroscopic or collective dynamics. In particular, active colloids exhibit accumulation at confining boundaries, upstream swimming in Poiseuille flow, and a reduced or negative apparent shear viscosity. My work has been focused on a theoretical and computational understanding of the dynamics of active colloids under the influence of confinement and external fluid flows, which are ubiquitous in biological processes. I consider the transport of active colloids in channel flows, the microrheology of active colloids, and lastly I propose and study a vesicle propulsion system based on the learned principles. A generalized Taylor dispersion theory is developed to study the transport of active colloids in channel flows. I show that the often-observed upstream swimming can be explained by the biased upstream reorientation due to the flow vorticity. The longitudinal dispersion of active colloids includes the classical shear-enhanced dispersion and an active swim diffusivity. Their coupling results in a non-monotonic variation of the dispersivity as a function of the flow speed. To understand the effect of particle shape on the transport of active colloids, a simulation algorithm is developed that is able to faithfully resolve the inelastic collision between an ellipsoidal particle and the channel walls. I show that the collision-induced rotation for active ellipsoids can suppress upstream swimming. I then investigate the particle-tracking microrheology of active colloids. I show that active colloids exhibit a swim-thinning microrheology and a negative microviscosity can be observed when certain hydrodynamic effects are considered. I show that the traditional constant-velocity probe model is not suitable for the quantification of fluctuations in the suspension. To resolve this difficulty, a generalized microrheology model that closely mimics the experimental setup is developed. I conclude by proposing a microscale propulsion system in which active colloids are encapsulated in a vesicle with a semi-permeable membrane that allows water to pass through. By maintaining an asymmetric number density distribution, I show that the vesicle can self-propel through the surrounding viscous fluid.</p
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