Design and Implementation of Electromagnetic Actuation System to Actuate Micro/NanoRobots in Viscous Environment

The navigation of Micro/Nanorobots (MNRs) with the ability to track a selected trajectory accurately holds significant promise for different applications in biomedicine, providing methods for diagnoses and treatments inside the human body. The critical challenge is ensuring that the required power can be generated within the MNR. Furthermore, ensuring that it is feasible for the robot to travel inside the human body with the necessary power availability. Currently, MNRs are widely driven either by exogenous power sources (light energy, magnetic fields, electric fields, acoustics fields, etc.) or by endogenous energy sources, such as chemical interaction energy. Various driving techniques have been established, including piezoelectric as a driving source, thermal driving, electro-osmotic force driven by biological bacteria, and micro-motors powered by chemical fuel. These driving techniques have some restrictions, mainly when used in biomedicine. External magnetic fields are another potential power source of MNRs. Magnetic fields can permeate deep tissues and be safe for human organisms. As a result, magnetic fields’ magnetic forces and moments can be applied to MNRs without affecting biological fluids and tissues. Due to their features and characteristics of magnetic fields in generating high power, they are naturally suited to control the electromagnetically actuated MNRs in inaccessible locations due to their ability to go through tiny spaces. From the literature, it can be inferred from the available range of actuation technologies that magnetic actuation performs better than other technologies in terms of controllability, speed, flexibility of the working environment, and far less harm may cause to people. Also, electromagnetic actuation systems may come in various configurations that offer many degrees of freedom, different working mediums, and controllability schemes. Although this is a promising field of research, further simulation studies, and analysis, new smart materials, and the development and building of new real systems physically, and testing the concepts under development from different aspects and application requirements are required to determine whether these systems could be implemented in natural clinical settings on the human body. Also, to understand the latest development in MNRs and the actuation techniques with the associated technologies. Also, there is a need to conduct studies and comparisons to conclude the main research achievements in the field, highlight the critical challenges waiting for answers, and develop new research directions to solve and improve the performance. Therefore, this thesis aims to model and analyze, simulate, design, develop, and implement (with complete hardware and software integration) an electromagnetic actuation (EMA) system to actuate MNRs in the sixdimensional (6D) motion space inside a relatively large region of interest (ROI). The second stage is a simulation; simulation and finite element analysis were conducted. COMSOL multi-physics software is used to analyze the performance of different coils and coil pairs for Helmholtz and Maxwell coil configurations and electromagnetic actuation systems. This leads to the following.: • Finite element analysis (FEA) demonstrates that the Helmholtz coils generate a uniform and consistent magnetic field within a targeted ROI, and the Maxwell coils generate a uniform magnetic gradient. • The possibility to combine Helmholtz and Maxwell coils in different space dimensions. With the ability to actuate an MNR in a 6D space: 3D as a position and 3D as orientation. • Different electromagnetic system configurations are proposed, and their effectiveness in guiding an MNR inside a mimicked blood vessel environment was assessed. • Three pairs of Helmholtz coils and three pairs of coils of Maxwell coils are combined to actuate different size MNRs inside a mimicked blood vessel environment and in 6D. Based on the modeling results, a magnetic actuation system prototype that can control different sizes MNRs was conceived. A closed-loop control algorithm was proposed, and motion analysis of the MNR was conducted and discussed for both position and orientation. Improved EMA location tracking along a chosen trajectory was achieved using a PID-based closed-loop control approach with the best possible parameters. Through the model and analysis stage, the developed system was simulated and tested using open- and closed-loop circumstances. Finally, the closedloop controlled system was concluded and simulated to verify the ability of the proposed EMA to actuate an MN under different trajectory tracking examples with different dimensionality and for different sizes of MNRs. The last stage is developing the experimental setup by manufacturing the coils and their base in-house. Drivers and power supplies are selected according to the specifications that actuate the coils to generate the required magnetic field. Three digital microscopes were integrated with the electromagnetic actuation system to deliver visual feedback aiming to track in real-time the location of the MNR in the 6D high viscous fluidic environment, which leads to enabling closed-loop control. The closed-loop control algorithm is developed to facilitate MNR trajectory tracking and minimize the error accordingly. Accordingly, different tests were carried out to check the uniformity of the magnetic field generated from the coils. Also, a test was done for the digital microscope to check that it was calibrated and it works correctly. Experimental tests were conducted in 1D, 2D plane, and 3D trajectories with two different MNR sizes. The results show the ability of the proposed EMA system to actuate the two different sizes with a tracking error of 20-45 µm depending on the axis and the size of the MNR. The experiments show the ability of the developed EMA system to hold the MNR at any point within the 3D fluidic environment while overcoming the gravity effects. A comparison was made between the results achieved (in simulation and physical experiments) and the results deduced from the literature. The comparison shows that the thesis’s outcomes regarding the error and MNR size used are significant, with better performance relative to the MNR size and value of the error

Self-powered mobile sensor for in-pipe potable water quality monitoring

Traditional stationary sensors for potable-water quality monitoring in a wireless sensor network format allow for continuous data collection and transfer. These stationary sensors have played a key role in reporting contamination events in order to secure public health. We are developing a self-powered mobile sensor that can move with the water flow, allowing real-time detection of contamination in water distribution pipes, with a higher temporal resolution. Functionality of the mobile sensor was tested for detecting and monitoring pH, Ca2+, Mg2+, HCO3-/CO32-, NH4+, and Clions. Moreover, energy harvest and wireless data transmission capabilities are being designed for the mobile sensor

DNA Origami Nanopores for Protein Biosensing

There is an increasing demand in biomedicine for rapid diagnostic testing. This is fuelled by the improved knowledge of the proteome and genome and a drive towards personalised medicine. Furthermore, many new potential biomarkers for diseases are being identified. Portable, point-of-care biosensors can meet these demands and take advantage of the recent biomedical developments. In this thesis, we investigate the creation of a biosensor element, including a design that allows the detection of protein biomarkers via an electrical label-free method. The use of nanopores for single molecule sensing has led to the development of commercially viable, portable, label-free DNA sequencing devices.1 However, the use of nanopores for detection of protein analytes is yet to reach the same viability. A reason for this is the inability for current nanopore materials to combine both atomically precise structural definition and tuneable nanopore size of the widths needed to accommodate protein analytes. In this thesis’s main project a route to overcome these limitations is described, by using the DNA origami technique. Multiple layers of DNA duplexes are interlinked to form a nanopore structure with a defined, predetermined central channel. The pore described can transport proteins with a higher fidelity than previously published work. Small DNA nanopores have shown promise for the transport of some small molecule analytes2,3,4. A secondary project looks at the use of a single loop of duplex associated with a lipid bilayer as a simplistic nanopore to induce ion transport through a membrane. Although consistent current steps were not demonstrated, the DNA loop was shown to associate with and cause some disruption and ion transport through the bilayer. Large DNA origami rings have been shown to template the formation of liposomes of a defined size5 . These rings, initially functionalised with lipid nucleation sites, were hypothesised to be adaptable for bilayer association and use in a nanopore sensing set up by replacing lipid nucleation sites with cholesterol molecules (lipid | 3 anchors) to induce bilayer association. Out of several anchor arrangements investigated one arrangement, with anchors located on the outside of the ring in the plane of the ring, was shown to be the most viable. By and large, only conductance values of a small magnitude were observed when single channel current recordings were conducted with the DNA origami rings in a Dphpc membrane. This suggested that association of the rings with the bilayer does not lead to the formation of a channel of the desired size. The origami funnel nanopore designed as the main aim of this thesis is of a form which is robust and versatile for further use. The DNA nanopore designed can be easily modified with additional functionalizations and is shown to associate with, and span, lipid bilayers. The nanopore can be used as a template from which further applications and advances in nanopore sensing research can be established

DNA-based artificial systems for mimicking membrane-related mechanisms and targeted delivery

Im Laufe der letzten zehn Jahre hat sich DNA durch die Selbstorganisation komplementärer Sequenz als sehr vielseitiges Baumaterial auf der Nanometer Skala bewährt. Die Struktur der DNA erlaubt die Konstruktion von beliebig geformten, nanometergroßen Objekten und die Modifizierung mit einer Vielzahl an (Bio-)Molekülen mit Nanometer Genauigkeit, definierter Orientierung und kontrollierbarer Stöchiometrie. In dieser Dissertation wurden DNA-basierte Nanostrukturen für die Nachahmung membranbedingter biologischer Ereignisse und zielgerichteter Transportapplikationen vorgestellt. Im ersten Teil der Arbeit wurden das Potenzial zur gezielten Verabreichung und die Stabilität der entworfenen DNA-Nanostrukturen in zellulärer Umgebung untersucht. Zu diesem Zweck wurden DNA-Nanoröhren durch ein einzelsträngiges DNA-Kachel-Anordnungs hergestellt und mit Folat-Molekülen und siRNA funktionalisiert um spezifisch Gene in Krebszellen, die den Folatrezeptor überexprimieren abzuschalten. In dieser Studie beobachteten wir, dass DNA-Nanoröhrchen zum Endosom geleitet wurden, aber nicht zum Cytosol der Krebszellen. Übereinstimmend mit dieser Beobachtung, konnte kein Abschalten der Zielgene detektiert werden. Darüber hinaus stießen wir auf einige Herausforderungen hinsichtlich der Stabilität der Strukturen, die bei der Anwendung in vivo berücksichtigt werden müssen. Im zweiten Teil wurde die hierarchische Anordnung von membrangebundenen DNA- Origami-Strukturen untersucht. Dazu wurden dreischichtige DNA-Origami-Blockstrukturen über Cholesterin-Moleküle an die Lipiddoppelschichten gebunden, die frei auf den Membranen diffundierten. Eindimensionale Polymere und zweidimensionale Gitter wurden durch programmierten Selbstorganisation der Strukturen auf den Membranen unter Verwendung verschiedener Sätze von Verbindungsoligonukleotiden gebildet. Weiterhin wurden DNA-Origami-Triskelione zu sechseckigen Gittern zusammengebaut, die der Bildung von Clathrin- Vesikeln während der Endozytose glichen. Darüber hinaus führt die Gitterbildung zu einer Verformung der Lipidmembranen, die auf das Potential des Systems für eine kontrollierbare Formgebung der Membranen aufzeigt. Die Studie zeigte, dass selbstorganisierte DNA-Origami-Strukturen die hierarchische Assemblierung von Multiproteinkomplexen auf zytoplasmatischen Membranen nachahmen könnte. Im letzten Teil wurde die Verwendung von DNA-Nanoröhrchen untersucht, eine Immunreaktion in vivo zu induzieren oder zu unterdrücken. In der ersten Studie wurden DNA-Nanoröhren mit unmethylierten Cytosin-Phosphat-Guanin-Oligodesoxynukleotiden (CpG-ODNs) funktionalisiert und in den Skelettmuskel anästhesierter Mäuse injiziert, um eine Immunstimulation gezielt herbeizuführen. Wir beobachteten, dass DNA-Nanoröhren durch gewebsständige Makrophagen internalisiert wurden und in den Endosomen akkumulierten. Nur Mikroinjektion von CpG-funktionalisierten DNA-Nanoröhren, aber nicht undekorierte Nanoröhren oder CpG-ODNs induzierte eine signifikante Rekrutierung von Leukozyten zur Injektionsstelle sowie eine Aktivierung des NF-κB-Signalweges. In der zweiten Studie wurden DNA-Nanoröhren mit dem anti-inflammatorischem Wirkstoff Dexamethason über i-Motivsequenz funktionalisiert. Wir haben gezeigt, dass die Strukturen die Leukozyten-Rekrutierung in das entzündete Gewebe aufgrund der i-Motiv-abhängigen Freisetzung von Dexamethason hemmen.!Over the last decade, DNA has proven to be an extremely versatile building material through the self-assembly of complementary oligonucleotides. The structure of DNA allows the construction of arbitrarily shaped objects in nanoscale which can be modified with a variety of (bio)molecules with nanometer precision, defined orientation and fully controlled stoichiometry. In this dissertation, DNA-based nanostructures were demonstrated for mimicking membrane-related biological events and targeted delivery applications. In the first part of the thesis, targeted delivery and the stability of the designed DNA nanostructures in the cellular environment were investigated. For this purpose, DNA nanotubes were produced via the single-stranded tile assembly method and functionalized with folate molecules and siRNA to specifically silence genes in folate receptor over- expressing cancer cells. In this study, we observed that DNA nanotubes reached to the endosome but not to the cytosol of the cancer cells.! Consistent with this observation, no silencing of the targeted gene could be detected. Furthermore, we encountered several challenges concerning the stability of the structures that have to be taken into account during in vivo delivery applications. In the second part, the hierarchical assembly of membrane-bound DNA origami structures was investigated. For this, three-layer DNA origami block structures were attached to the lipid bilayers via cholesterol molecules and diffused freely on the membranes. One-dimensional polymers and two-dimensional lattices were formed upon the programmed self-assembly of the structures on the membranes using different sets of connector oligonucleotides. DNA origami triskelions further assembled into hexagonal lattices that resembled the formation of clathrin-coated pits during endocytosis. Moreover, the lattice formation leads to deformation of the lipid membranes that indicates the potential of the system towards controllable sculpting of the membranes. The study demonstrated that self-assembled DNA origami structures could mimic the hierarchical assembly of multi-protein complexes on cytoplasmic membranes. In the last part, we investigated the use of DNA nanotubes to induce or suppress the immune reactions in vivo. In the first study, DNA nanotubes were functionalized with unmethylated cytosine-phsophate-guanine oligodeoxynucleotides (CpG ODNs) and microinjected into the skeletal muscle of anesthetized mice to induce immune stimulation. We observed that DNA nanotubes were internalized by tissue-resident macrophages and accumulated in their endosomes. Only microinjection of CpG functionalized DNA nanotubes but not of plain nanotubes or unfolded CpG ODNs induced the significant recruitment of leukocytes to the injection site as well as the activation of the NF-κB pathway. In the second study, DNA nanotubes were functionalized with the anti-inflammatory drug dexamethasone via an i-motif sequence. We demonstrated that these structures inhibited the leukocyte recruitment into the inflammed tissue due to the i-motif dependent release of dexamethasone.

Nucleic Acid Architectures for Therapeutics, Diagnostics, Devices and Materials

Nucleic acids (RNA and DNA) and their chemical analogs have been utilized as building materials due to their biocompatibility and programmability. RNA, which naturally possesses a wide range of different functions, is now being widely investigated for its role as a responsive biomaterial which dynamically reacts to changes in the surrounding environment. It is now evident that artificially designed self-assembling RNAs, that can form programmable nanoparticles and supra-assemblies, will play an increasingly important part in a diverse range of applications, such as macromolecular therapies, drug delivery systems, biosensing, tissue engineering, programmable scaffolds for material organization, logic gates, and soft actuators, to name but a few. The current exciting Special Issue comprises research highlights, short communications, research articles, and reviews that all bring together the leading scientists who are exploring a wide range of the fundamental properties of RNA and DNA nanoassemblies suitable for biomedical applications

Bio-Inspired Soft Artificial Muscles for Robotic and Healthcare Applications

Soft robotics and soft artificial muscles have emerged as prolific research areas and have gained substantial traction over the last two decades. There is a large paradigm shift of research interests in soft artificial muscles for robotic and medical applications due to their soft, flexible and compliant characteristics compared to rigid actuators. Soft artificial muscles provide safe human-machine interaction, thus promoting their implementation in medical fields such as wearable assistive devices, haptic devices, soft surgical instruments and cardiac compression devices. Depending on the structure and material composition, soft artificial muscles can be controlled with various excitation sources, including electricity, magnetic fields, temperature and pressure. Pressure-driven artificial muscles are among the most popular soft actuators due to their fast response, high exertion force and energy efficiency. Although significant progress has been made, challenges remain for a new type of artificial muscle that is easy to manufacture, flexible, multifunctional and has a high length-to-diameter ratio. Inspired by human muscles, this thesis proposes a soft, scalable, flexible, multifunctional, responsive, and high aspect ratio hydraulic filament artificial muscle (HFAM) for robotic and medical applications. The HFAM consists of a silicone tube inserted inside a coil spring, which expands longitudinally when receiving positive hydraulic pressure. This simple fabrication method enables low-cost and mass production of a wide range of product sizes and materials. This thesis investigates the characteristics of the proposed HFAM and two implementations, as a wearable soft robotic glove to aid in grasping objects, and as a smart surgical suture for perforation closure. Multiple HFAMs are also combined by twisting and braiding techniques to enhance their performance. In addition, smart textiles are created from HFAMs using traditional knitting and weaving techniques for shape-programmable structures, shape-morphing soft robots and smart compression devices for massage therapy. Finally, a proof-of-concept robotic cardiac compression device is developed by arranging HFAMs in a special configuration to assist in heart failure treatment. Overall this fundamental work contributes to the development of soft artificial muscle technologies and paves the way for future comprehensive studies to develop HFAMs for specific medical and robotic requirements

EUROSENSORS XVII : book of abstracts

Fundação Calouste Gulbenkien (FCG).Fundação para a Ciência e a Tecnologia (FCT)

Ideas Exchange: Design and the post bio-tech-body

This thesis situates speculative design as a valuable tool for thinking about design issues and the body. Bringing together historical, theoretical criticism and practice to show that speculative design is intimately linked with the body. The thesis’ arguments build on the basis that both the body and design have gone through a processes of anatomisation: they have been dissected, separated and segmented into parts and terms. Those parts and terms are then ordered in a fashion which may not necessarily be advantageous intra-disciplinarily, that is for collaborations and discussions within a discipline. A different anatomisation is proposed for more contemporary models of design where the frequent use of relative points of reference is evident, in particular in respect to speculative design. This model in which speculative design is considered as adjunct allows designers to more freely share resources with other disciplines at their converging membranes and through doing so that design itself in these new iterations may be considered a useful investigative instrument for exchanging ideas. Taking a ‘research through design’ approach, the text is informed by a portfolio of practice-based works that reveal the complex continuing relationship between design and the body. The eight original design works made for this thesis present body imaginaries influenced by technological change. The methods used to create the design outputs involved collaborative research and residencies which ultimately advocates the refinement of particular communicative tactics in speculative design. These tactics are outlined as a way to develop a sensibility for myself and those wishing to engage with the current zeitgeist of models of the body and design that may eventually be useful in fostering an ongoing exchange between them so that new forms may evolve in both body and design criticism