36 research outputs found
Current status and future application of electrically controlled micro/nanorobots in biomedicine
Using micro/nanorobots (MNRs) for targeted therapy within the human body is an emerging research direction in biomedical science. These nanoscale to microscale miniature robots possess specificity and precision that are lacking in most traditional treatment modalities. Currently, research on electrically controlled micro/nanorobots is still in its early stages, with researchers primarily focusing on the fabrication and manipulation of these robots to meet complex clinical demands. This review aims to compare the fabrication, powering, and locomotion of various electrically controlled micro/nanorobots, and explore their advantages, disadvantages, and potential applications
The study of renal function and toxicity using zebrafish (Danio rerio) larvae as a vertebrate model
Zebrafish (Danio rerio) is a powerful model in biomedical and pharmaceutical sciences. The zebrafish model was introduced to toxicological sciences in 1960, followed by its use in biomedical sciences to investigate vertebrate gene functions. As a consequence of many research projects in this field, the study of human genetic diseases became instantly feasible. Consequently, zebrafish have been intensively used in developmental biology and associated disciplines. Due to the simple administration of medicines and the high number of offspring, zebrafish larvae became widely more popular in pharmacological studies in the following years. In the past decade, zebrafish larvae were further established as a vertebrate model in the field of pharmacokinetics and nanomedicines. In this PhD thesis, zebrafish larvae were investigated as an earlystage in vivo vertebrate model to study renal function, toxicity, and were applied in drug-targeting projects using nanomedicines.
The first part focused on the characterization of the renal function of three-to four-dayold zebrafish larvae. Non-renal elimination processes were additionally described. Moreover, injection techniques, imaging parameters, and post-image processing scripts were established to serve as a toolbox for follow-up projects.
The second part analyzed the impact of gentamicin (a nephrotoxin) on the morphology of the pronephros of zebrafish larvae. Imaging methodologies such as fluorescent-based laser scanning microscopy and X-ray-based microtomography were applied. A profound comparison study of specimens acquired with different laboratory X-ray-based microtomography devices and a radiation facility was done to promote the use of X-ray-based microtomography for broader biomedical applications.
In the third part, the toxicity of nephrotoxins on mitochondria in renal epithelial cells of proximal tubules was assessed using the zebrafish larva model. Findings were compared with other teleost models such as isolated renal tubules of killifish (Fundulus heteroclitus). In view of the usefulness and high predictability of the zebrafish model, it was applied to study the pharmacokinetics of novel nanoparticles in the fourth part. Various in vivo pharmacokinetic parameters such as drug release, transfection of mRNA/pDNA plasmids, macrophage clearance, and the characterization of novel drug carriers that were manipulated with ultrasound were assessed in multiple collaborative projects.
Altogether, the presented zebrafish model showed to be a reliable in vivo vertebrate model to assess renal function, toxicity, and pharmacokinetics of nanoparticles. The application of the presented model will hopefully encourage others to reduce animal experiments in preliminary studies by fostering the use of zebrafish larvae
Analysis, Design and Fabrication of Micromixers, Volume II
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
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
New Trends and Applications in Femtosecond Laser Micromachining
This book contains the scientific contributions to the Special Issue entitled: "New Trends and Applications in Femtosecond Laser Micromachining". It covers an array of subjects, from the basics of femtosecond laser micromachining to specific applications in a broad spectra of fields such biology, photonics and medicine
The development of optical nanomachines for studying molecules : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Mechatronics Engineering at Massey University, Palmerston North, New Zealand
Chapter 3 is ©2020 IEEE. Accepted manuscript is reprinted, with permission, from 2020 IEEE/ASME International Conference on Advanced Intelligent Mechatronics (AIM). Chapter 5 is ©2022 IEEE. Accepted manuscript is reprinted, with permission, from 2022 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS).Optical tweezers have been used for a number of applications since their invention by Arthur Ashkin in 1986, and are particularly useful for biological and biophysical studies due to their exceptionally high spatial and force-based resolution. The same intense laser focus that allows light to be used as a tool for micro-nanoscale manipulation also has the potential to damage the objects being studied, and the extremely high force resolution is coupled with the limitation of very low forces. There is potential to overcome these drawbacks of optical manipulation through making use of another laser based technique: two-photon absorption polymerisation (TPAP). This thesis has brought these together to demonstrate the uses of optical nanomachines as helpful tools for optical tweezer studies. The project was highly interdisciplinary, concerning the intersection of optical trapping, 3D micromachine design and development, and DNA stretching. The thesis was based around the strategy of first developing microrobots and demonstrating their manipulation using optical tweezers, then adjusting the design for specific applications. Microlevers were developed for lever-assisted DNA stretching and amplification of optical forces. The influence of design features and TPAP parameters on microlever functionality was investigated; particularly the influence of overlapping area and presence of supports, and the effects of differently shaped "trapping handles". These features were important as lever functionality was tested in solutions of different ionic strength, and stable trapping of the levers was required for force amplification. DNA stretching was chosen as a target application for distanced-application of optical forces due to its status as a well-known and characterised example of single-molecule studies with optical tweezers. Amplification of optical forces was also seen as an application that could demonstrate the utility of optical micromachines, and microlevers with a 2:1 lever arm ratio were developed to produce consistent, two-fold amplification of optical forces, in a first for unsupported, pin-jointed optical microrobotics. It is hoped that in the future fully-remote, micromachine-assisted studies will extend optical tweezer studies of laser-sensitive subjects, as well as increasing the forces that can be applied, and the results obtained in this thesis are encouraging. All in all, the thesis confirms the potential of optical micromachines for aiding studies using optical tweezers, and demonstrates concrete progress in both design and application
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High-performance artificial micro/nanomachines and their bioapplications
Artificial micro/nanomachines are micrometer or nanometer scale mechanical devices that convert diverse energy sources into controlled mechanical motions. The development and applications of these micro/nanomachines are among the most pressing challenges in the research field of nanoscience and nanotechnology. In this dissertation, we report innovative designs and operations of artificial micro/nanomachines for bioapplications in biochemical sensing, biomolecule capture, drug delivery and release. Based on the electric tweezers, innovative rotary nanomotors are bottom-up assembled with high efficiency from nanoscale building blocks, which are massively fabricated and less than 1 μm in all dimensions. After assembling, the rotary nanomotors achieve an ultrafast speed up to 18,000 rpm, an ultradurable operation lifetime of 80 hours, and over 1.1 million rotation cycles. To explore diverse alternative energy inputs for nanomotors, we also applied electric tweezers in the guided manipulation of chemical nanomotors: the motions of chemical nanomotors are aligned along the direction of AC electric fields and their speeds are modulated by the DC electric fields. The prowess of the manipulation of chemical nanomotors by the electric tweezers is demonstrated for applications in cargo delivery to designated microdocks and assembling of chemical nanomotors for powering rotary nanoelectromechanical system (NEMS) devices. To integrate the function of Raman sensing on the micro/nanomachines, plasmonic nanomotors and bio-photonic-plasmonic micromotors with silver (Ag) nanoparticle coating are designed and fabricated, which provide ultrasensitive detection of biochemicals by Surface-enhanced Raman spectroscopy (SERS). The plasmonic nanomotors are designed with nanoporous superstructures, providing high capacities of drug loading and large numbers of hotspots. The plasmonic nanomotors also actively manipulate molecules and tune the release rate in electric fields due to the induced electrokinetic effect. The bio-photonic-plasmonic micromotors based on biosilica diatom frustules are applied in the capture and detection of DNA molecules, which are significantly accelerated during the rotation of the micromotors. The fundamental mechanism is investigated and attributed to the reduction of Nernst diffusion layer caused by the rotation. The innovations of artificial micro/nanomachines including concept, design, fabrication, manipulation, and bioapplications in this dissertation, are expected to inspire various research areas including NEMS, nanorobotics, microfluidics, biochemical delivery, and diagnostic sensingMaterials Science and Engineerin