Magnetically Driven Micro and Nanorobots

Manipulation and navigation of micro and nanoswimmers in different fluid environments can be achieved by chemicals, external fields, or even motile cells. Many researchers have selected magnetic fields as the active external actuation source based on the advantageous features of this actuation strategy such as remote and spatiotemporal control, fuel-free, high degree of reconfigurability, programmability, recyclability, and versatility. This review introduces fundamental concepts and advantages of magnetic micro/nanorobots (termed here as "MagRobots") as well as basic knowledge of magnetic fields and magnetic materials, setups for magnetic manipulation, magnetic field configurations, and symmetry-breaking strategies for effective movement. These concepts are discussed to describe the interactions between micro/nanorobots and magnetic fields. Actuation mechanisms of flagella-inspired MagRobots (i.e., corkscrew-like motion and traveling-wave locomotion/ciliary stroke motion) and surface walkers (i.e., surface-assisted motion), applications of magnetic fields in other propulsion approaches, and magnetic stimulation of micro/nanorobots beyond motion are provided followed by fabrication techniques for (quasi)spherical, helical, flexible, wire-like, and biohybrid MagRobots. Applications of MagRobots in targeted drug/gene delivery, cell manipulation, minimally invasive surgery, biopsy, biofilm disruption/eradication, imaging-guided delivery/therapy/surgery, pollution removal for environmental remediation, and (bio)sensing are also reviewed. Finally, current challenges and future perspectives for the development of magnetically powered miniaturized motors are discussed

Electrochemistry: A basic and powerful tool for micro- and nanomotor fabrication and characterization

Electrochemistry, although an ancient field of knowledge, has become of paramount importance in the synthesis of materials at the nanoscale, with great interest not only for fundamental research but also for practical applications. One of the promising fields in which electrochemistry meets nanoscience and nanotechnology is micro/nanoscale motors. Micro/nano motors, which are devices able to perform complex tasks at the nanoscale, are commonly multifunctional nanostructures of different materials - metals, polymers, oxides- and shapes -spheres, wires, helices- with the ability to be propelled in fluids. Here, we first introduce the topic of micro/nanomotors and make a concise review of the field up to day. We have analyzed the field from different points of view (e.g. materials science and nanotechnology, physics, chemistry, engineering, biology or environmental science) to have a broader view of how the different disciplines have contributed to such exciting and impactful topic. After that, we focus our attention on describing what electrochemical technology is and how it can be successfully used to fabricate and characterize micro/nanostructures composed of different materials and showing complex shapes. Finally, we will review the micro and nanomotors fabricated using electrochemical techniques with applications in biomedicine and environmental remediation, the two main applications investigated so far in this field. Thus, different strategies have thus been shown capable of producing core-shell nanomaterials combining the properties of different materials, multisegmented nanostructures made of, for example, alternating metal and polymer segments to confer them with flexibility or helicoidal systems to favor propulsion. Moreover, further functionalization and interaction with other materials to form hybrid and more complex objects is also shown

Elastic Tail Propulsion at Low Re

The use of microswimmers, or microscopic swimming robots, in the medical field is becoming more sought after for applications such as targeted drug delivery and microsurgery. While such microswimmers do not yet exist for use on patients, many researchers are working on this front to make them a reality. One of the main challenges in making these microswimmers a reality is creating propulsion in a low Reynolds number environment. This project aims to create and test a prototype of a swimmer which employs 3D circular movement of its tail for propulsion in a very viscous fluid, mimicking a low Reynolds environment in the macroscale. To create a successful proof of concept of 3D circular propulsion, simulations, prototyping, and experimental evaluation of the prototype were conducted during the course of this project. Finite element analysis using the commercial software COMSOL was conducted to design a swimmer tail that would generate a positive thrust force, and a velocity at an order of magnitude consistent with the analytical prediction. Guided by the simulation results, a prototype was fully realized, and testing was conducted resulting in a speed of 0.5 mm/s, which matched with the order of magnitude of the speed obtained from the simulations. The data collected from testing accompanied by simulations confirmed our proof of concept. Lastly, additional simulations were performed to find optimal parameters that can be implemented in the swimmer design for future testing. In essence, this report will provide an overview of the design, construction, and testing of a scaled-up experimental platform to examine the principle of elastic propulsion in highly viscous fluid

Light controlled motility of Escherichia coli. Characterization and applications

Characterization of wild type E. coli motility in response to light stimuli. Gene editing of bacteria to implement specifc functions (e.g. photokinesis). The engineered strain has been used to demonstrate that density modulation of photokinetic bacteria can be obtained by projecting spatially structured light on the sample. Additionally these bacteria have been also used as propelling units in microfabricated structures

Modelling the transport of nanoparticles across the blood-brain barrier using an agent-based approach

Diseases affecting the Central Nervous System (CNS), consisting of the brain and spinal cord, will account for an estimated 11.84% of all deaths by 2015, with few effective treatment options. This is partly a consequence of poor penetrance of blood-borne molecules, including almost all therapeutics, into the CNS. This is due to the existence of a blood-brain barrier, severely limiting potential therapeutic intervention. Nanoparticles are diverse nanoscale particles that have recently been demonstrated to be able to improve drug penetrance across the blood-brain barrier, by targeting endogenous transport systems. However, further methods to improve their general delivery to the CNS and specific delivery to different regions of the CNS are required. Here, agent-based modelling has been utilised to simulate blood flow in a capillary at the blood-brain barrier. This modelling approach has demonstrated the importance of a number of biological, physiological and physical factors that affect nanoparticle uptake to the CNS. This model was used to demonstrate how the fluid dynamics in capillaries enhances nanoparticle distribution to the vessel wall interface. These simulations have demonstrated that by tuning nanoparticle properties, including ligand density, receptor-ligand affinity and size, general delivery by transcytosis can be improved. Moreover, particular nanoparticle formulations can target high levels, but not low levels, of receptor expression at the blood-brain barrier thus providing a method to improve specific delivery into particularly CNS regions. Furthermore, nanoparticles can be formulated to stabilise nanoparticle binding under different flow conditions. In particular during regional blood flow increases, called functional hyperaemia, which aid access of nutrients to that region of the CNS. It is predicted from these simulations that this could be harnessed to further improve specificity of delivery. Finally, chemotactic nanoparticles are shown to have an improved distribution to the vessel wall interface and penetration through the CNS tissue

Flowing matter

This open access book, published in the Soft and Biological Matter series, presents an introduction to selected research topics in the broad field of flowing matter, including the dynamics of fluids with a complex internal structure -from nematic fluids to soft glasses- as well as active matter and turbulent phenomena.Flowing matter is a subject at the crossroads between physics, mathematics, chemistry, engineering, biology and earth sciences, and relies on a multidisciplinary approach to describe the emergence of the macroscopic behaviours in a system from the coordinated dynamics of its microscopic constituents.Depending on the microscopic interactions, an assembly of molecules or of mesoscopic particles can flow like a simple Newtonian fluid, deform elastically like a solid or behave in a complex manner. When the internal constituents are active, as for biological entities, one generally observes complex large-scale collective motions. Phenomenology is further complicated by the invariable tendency of fluids to display chaos at the large scales or when stirred strongly enough. This volume presents several research topics that address these phenomena encompassing the traditional micro-, meso-, and macro-scales descriptions, and contributes to our understanding of the fundamentals of flowing matter.This book is the legacy of the COST Action MP1305 “Flowing Matter”

Nanosistemas híbridos para la administración de agentes terapéuticos como tratamiento de enfermedades complejas

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Química en Ciencias Farmacéuticas, leída el 05-07-2021The overall objective of this doctoral thesis has been the design of various nanomaterials with the aim of addressing distinct approaches to treat cancer and fibrosis, as well as overcoming some of the biological barriers that restrict nanomedicine-based therapies.These biological restrictions entail important limitations in the fight against cancer based on nanomedicines. Some of them are the sequestration of nanoparticles by the mononuclear phagocytic system, the lack of selectivity of conventional chemotherapy, which generates undesirable side-effects and disfunctions in organs or tissues, or the scarce penetration of nanoparticles within the target diseased tissue. Recent interest in the design of nanosystems that overcome these constraints is generating new tools for the effective treatment of cancer, as well as other pathologies...El objetivo general de esta tesis doctoral ha sido el diseño de varios nanomateriales con el fin de abordar distintos enfoques para tratar el cáncer y la fibrosis, así como superar algunas de las barreras biológicas que restringen las terapias basadas en el uso de nanomedicinas. Estas restricciones biológicas suponen importantes limitaciones en la lucha contra el cáncer basada en nanomedicinas. Algunas de ellas son el secuestro de las nanopartículas por el sistema fagocítico mononuclear, la falta de selectividad de la quimioterapia convencional, que genera efectos secundarios y disfunciones en órganos o tejidos, o la escasa penetración de las nanopartículas en el tejido enfermo objetivo. El reciente interés en el diseño de nanosistemas que superen estas restricciones está generando nuevas herramientas para el tratamiento eficaz del cáncer, así como también de otras patologías...Fac. de FarmaciaTRUEunpu

Emergent structure formation of the actin cytoskeleton

Anders als menschengemachte Maschinen verfügen Zellen über keinen festgeschriebenen Bauplan und die Positionen einzelner Elemente sind häufig nicht genau festgelegt, da die Moleküle diffusiven Zufallsbewegungen unterworfen sind. Darüber hinaus sind einzelne Bauteile auch nicht auf eine einzelne Funktion festgelegt, sondern können parallel in verschiedene Prozesse einbezogen sein. Basierend auf Selbstorganisation und Selbstassemblierung muß die Organisation von Anordnung und Funktion einer lebenden Zelle also bereits in ihren einzelnen Komponenten inhärent enthalten sein. Die intrazelluläre Organisation wird zum großen Teil durch ein internes Biopolymergerüst reguliert, das Zytoskelett. Biopolymer-Netzwerke und –Fasern durchdringen die gesamte Zelle und sind verantworlich für mechanische Integrität und die funktionale Architektur. Unzählige essentielle biologische Prozesse hängen direkt von einem funktionierenden Zytoskelett ab. Die vorliegende Arbeit zielt auf ein besser Verständnis und den Nachbau zweier verschiedener funktionaler Module lebender Zellen anhand stark reduzierter Modellsysteme. Als zentrales Element wurde Aktin gewählt, da dieses Biopolymer eine herausragende Rolle in nahezu allen eukaryotischen Zellen spielt. Mit dem ersten Modellsystem wird der bewegliche Aktin-Polymerfilm an der Vorderkante migrierender Zellen betrachtet. Die wichtigsten Elemente dieser hochdynamischen Netzwerke sind bereits bekannt und wurden in dieser Arbeit benutzt um ein experimentelles Modellsystem zu etablieren. Vor allem aber lieferten detailierte Computersimulationen und ein mathematisches Modell neue Erkenntnisse über grundlegende Organisationsprinzipien dieser Aktinnetzwerke. Damit war es nicht nur möglich, experimentelle Daten erfolgreich zu reproduzieren, sondern das Entstehen von Substrukturen und deren Charakteristika auf proteinunabhängige, generelle Mechanismen zurückzuführen. Das zweite studierte System betrachtet die Selbstassemblierung von Aktinnetzwerken durch entropische Kräfte. Aktinfilamente aggregieren hierbei durch Kondensation multivalenter Ionen oder durch Volumenausschluss hochkonzentrierter inerter Polymere. Ein neu entwickelter Experimentalaufbau bietet die Möglichkeit in gut definierten zellähnlichen Volumina, Konvektionseinflüsse zu umgehen und Aggregationseffekte gezielt einzuschalten. Hierbei wurden neuartige, regelmäßige Netzwerkstrukturen entdeckt, die bislang nur im Zusammenhang mit molekularen Motoren bekannt waren. Es konnte ferner gezeigt werden, dass die Physik der Flüssigkristalle entscheidend zu weiteren Variationen dieser Netzwerke beiträgt. Dabei wird ersichtlich, dass entstehende Netzwerke in ihrer Architektur direkt die zuvor herrschenden Anisotropien der Filamentlösung widerspiegeln.:1 Introduction 1 2 General background 7 2.1 General concepts 7 2.1.1 Coarse-graining as hierarchical reduction 8 2.1.2 Functional modules and redundancies 10 2.1.3 Emergence 11 2.1.4 Self-organization and self-assembly 13 2.1.5 Bottom-up and top-down 13 2.2 The cytoskeleton 15 2.2.1 From actin monomers to filaments 16 2.2.2 Accessory proteins and actin networks 21 2.3 Biopolymer pattern formation 25 2.3.1 Random networks and nematic phases 25 2.3.2 Linker and motor induced networks 28 3 Lamellipodial actin network formation 33 3.1 Background: crawling cell migration 33 3.1.1 Leading edge actin structures 35 3.1.2 Lamellipodial self-organization into oriented branches? 40 3.1.3 Lamellipodial modeling 41 3.1.4 Beyond the lamellipodium: adhesion and network contraction 42 3.2 Methods: lamellar treadmilling model 45 3.2.1 Assumptions 45 3.2.2 Choice of model parameters 51 3.2.3 Computer simulation (implementation) 52 3.2.4 Mathematical modeling 56 3.3 Modeling results 63 3.3.1 Reproduction of motile cell characteristics 64 3.3.2 Self-organization into lamellipodium and lamellum 65 3.3.3 Filament severing and annealing influence network properties 70 3.3.4 Unconfined network growth 74 3.4 Feasible model extensions 76 3.4.1 Alternative nucleation mechanisms 77 3.4.2 Convergence zone through myosin-driven network contraction 80 3.5 Experimental bottom-up approach 82 3.6 Discussion: Arp2/3 induced actin networks 87 4 Actin network patterns in confined systems 91 4.1 Background: counterion condensation and depletion forces 91 4.1.1 Actin, a polyelectrolyte: counterion condensation 92 4.1.2 Actin and molecular crowding: depletion forces 95 4.2 Methods: Experimental design and data analysis 97 4.2.1 Protein purification and handling 98 4.2.2 Droplet formation 98 4.2.3 Volume monitoring and pattern analysis 100 4.3 Actin pattern formation 105 4.3.1 Counterion-induced network formation 105 4.3.2 Depletion force induced network formation 111 4.4 First modeling attempts: bundling simulation 116 4.4.1 Model concept and assumptions 116 4.5 Discussion: Counterion and depletion-based network assembly 119 5 Discussion & Outlook 125 Appendix 129 A. Variation of filament orientation 129 B. Analytical solution of the mathematical model 131 C. Pre-alignment of filaments 132 D. Protocols 134 d1. Acetone Powder Prep 134 d2. Actin prep 135 d3. Actin labling with rhodamine dye 137 Bibliography 141 Acknowledgements 15

Synthesis of new pyrazolium based tunable aryl alkyl ionic liquids and their use in removal of methylene blue from aqueous solution

In this study, two new pyrazolium based tunable aryl alkyl ionic liquids, 2-ethyl-1-(4-methylphenyl)-3,5- dimethylpyrazolium tetrafluoroborate (3a) and 1-(4-methylphenyl)-2-pentyl-3,5-dimethylpyrazolium tetrafluoroborate (3b), were synthesized via three-step reaction and characterized. The removal of methylene blue (MB) from aqueous solution has been investigated using the synthesized salts as an extractant and methylene chloride as a solvent. The obtained results show that MB was extracted from aqueous solution with high extraction efficiency up to 87 % at room temperature at the natural pH of MB solution. The influence of the alkyl chain length on the properties of the salts and their extraction efficiency of MB was investigated