Characterization and control of artificial magnetotactic tetrahymena pyriformis

Micro-scale robotic systems have drawn a great deal of interest from researchers for their potential applications. Emerging areas, such as micromanufacturing and biosensing, look to integrate micro-scale robotics with biofactory-on-a-chip systems to solve engineering problems. To accomplish this goal, robots must be developed to work in a variety of micro-scale environments. This has led to the creation of artificial and biological microrobots. Artificial microrobots are expensive and challenging to produce as well as power. Alternatively, biological microrobots employ microorganisms that are easily and inexpensively cultured. Microorganisms also draw chemical energy from their surround environment eliminating the need for a power source. This makes microorganisms, such as Tetrahymena pyriformis (T. pyriformis), an appealing choice to use as microrobots.In this thesis, the utilization of T. pyriformis as a microrobot or cellular robot is demonstrated. The technique for culturing and fabricating magnetotactic cells is described. The experimental setup allowing for observation and control of T. pyriformis using magnetotaxis is presented. T. pyriformis swimming parameters are then characterized and applied to control the cells for engineering tasks. This work shows that T. pyriformis is a great candidate to be used as a cellular robot.M.S., Mechanical Engineering -- Drexel University, 201

MRI-Based Tumour Targeting Enhancement with Magnetotactic Bacterial Carriers

RÉSUMÉ Le cancer constitue la première cause de mortalité au Québec, avec 20,000 décès estimés par année. Parmi tous les patients atteints du cancer, une grande proportion pourrait profiter de l’avancement technologique en ce qui concerne le transport de médicaments. En effet, l’un des meilleurs moyens d’augmenter l’efficacité d’un médicament contre le cancer, tout en réduisant sa toxicité sur les cellules saines, est de le diriger vers la tumeur et de le maintenir à cet endroit jusqu’à ce qu’un effet thérapeutique se produise. Le transport ciblé de médicaments vers la tumeur peut considérablement améliorer l’efficacité thérapeutique, surtout si le transporteur est capable d’atteindre les zones nécrotiques et se répartir uniformément dans la zone à traiter. Les bactéries, de par leur motilité, sont d’excellents candidats pour une telle application, surtout qu’elles peuvent aussi être facilement fonctionnalisées. Ainsi, la recherche sur le traitement du cancer utilisant des bactéries s’est imposée comme une approche prometteuse surtout qu’elle pallie à une limitation majeure de la chimiothérapie et de la radiothérapie en permettant le traitement des zones anaérobies. Alors que des laboratoires à travers le monde tentent de fabriquer des systèmes miniatures en se basant sur le modèle bactérien, nous avons opté pour l’utilisation des bactéries qui existent dans la nature. Notre stratégie a été de trouver un système biologique ayant les caractéristiques essentielles (e.x. diamètre total de moins de deux micromètres, force de poussée de plus de 4 pN, etc.) et de concentrer nos efforts à identifier une interface et une méthode permettant son contrôle pour des fins de ciblages thérapeutiques dans les lésions tumorales. Nous avons identifié les bactéries magnétotactiques de type MC-1 comme le meilleur transporteur potentiel de médicaments pour le ciblage du cancer. Les MC-1 sont à la fois dirigeables par champs magnétiques et anaérobies, ce qui leur donne un grand avantage par rapport aux bactéries traditionnellement utilisées pour le ciblage du cancer. Le ciblage du cancer avec des bactéries exploite le plus souvent l’affinité des bactéries anaérobies à la région nécrotique faible en oxygène de la tumeur. Certes, ce ciblage manque de spécificité et un des problèmes le plus reconnu est la nécessité d’injecter une forte dose de bactéries pour assurer une croissance de celles-ci à l’intérieur de la tumeur. Ceci n’est pas le cas avec les MC-1 car elles sont à la fois anaérobies et magnétotactiques grâce à une chaîne de nanoparticules d’environ 70 nanomètres de diamètre, formant une sorte de « nano-boussole » magnétique à----------ABSTRACT Magnetotactic Bacteria (MTB) are being explored as potential drug transporters to solid tumours. The MTB’s active motility combined with magnetotaxism (their ability to swim following the direction of a magnetic field) offer new and potentially more accurate solutions in delivering drugs to tumours. In fact, the flagella bundles of the MC-1 bacteria (with an overall ideal cell diameter of approximately 50% the diameter of the tiniest human blood vessels) provide 4.0 to 4.7pN of thrust force for propulsion (roughly 10 times the value of many other well-known flagellated bacteria). Since there are no existing methods or technologies capable of inducing an equivalent force on a carrier of appropriate size for traveling inside a tumour’s microvasculature, live microorganisms are considered as a viable option. Many of the parameters in a tumour microenvironment, such as malformed angiogenesis capillaries, heterogeneous blood flow, and high interstitial pressure, hinder the delivery of blood-borne drugs to the affected area. Active motility might prove to be helpful in bypassing these limitations and may facilitate the uniform distribution of the drug in the targeted area. An MTB navigation technique that allows targeting without prior knowledge of the exact architecture of the vessels network has been developed. This navigation technique exploits both the ability of the MTB to swim following an imposed magnetic field and their random, continuous motion at low magnetic fields. Firstly, a focused magnetic field on the target sets the overall direction of the bacteria. Then, as the bacteria approach the targeted zone, the intensity of the magnetic field is decreased, which allows better bacteria repartition by exploiting their free motion. An additional approach that enhances MTB targeting relies on modulating the magnetic field direction in time, while keeping the magnetic field lines pointed toward the target. Navigation experiments in complex micro-channel networks highlight this process, where the successful targeting of bacteria is demonstrated when an appropriate magnetic field algorithm is applied, especially when it takes into account the nature of the channel network. Tridimensional control and navigation of MTB is also possible with the same technique through proper powering of the magnetic coils. In fact, by controlling their magnetic environment, it is possible to form a swarm of MTB, control its size and position within a given volume using a computer program

MRI-Based Communication with Untethered Intelligent Medical Microrobots

RESUME Les champs magnétiques présent dans un système clinique d’Imagerie par Résonance Magnétique (IRM) peuvent être exploités non seulement, afin d’induire une force de déplacement sur des microrobots magnétiques tout en permettant l’asservissement de leur position - une technique connue sous le nom de Navigation par Résonance Magnétique (NRM), mais aussi pour mettre en œuvre un procédé de communication. Pour des microrobots autonomes équipés de senseurs ayant un certain niveau d'intelligence et opérant à l'intérieur du corps humain, la puissance de transmission nécessaire pour communiquer des informations à un ordinateur externe par des méthodes présentement connues est insuffisante. Dans ce travail, une technique est décrite où une telle perte de puissance d'émission en raison de la mise à l'échelle de ces microrobots peut être compensée par le scanner IRM agissant aussi comme un récepteur très sensible. La technique de communication prend la forme d'une modification de la fréquence du courant électrique circulant le long d'une bobine miniature incorporé dans un microrobot. La fréquence du courant électrique peut être réglée à partir d'une entrée de seuil prédéterminée du senseur mis en place sur le microrobot. La fréquence devient alors corrélée à l’information de l’état du senseur recueilli par le microrobot et elle est déterminée en utilisant l'IRM. La méthode proposée est indépendante de la position et l'orientation du microrobot et peut être étendue à un grand nombre de microrobots pour surveiller et cartographier les conditions physiologiques spécifiques dans une région plus vaste à n’importe quelle profondeur à l'intérieur du corps.----------ABSTRACT The magnetic environment provided by a clinical Magnetic Resonance Imaging (MRI) scanner can be exploited to not only induce a displacement force on magnetic microrobots while allowing MR-tracking for serving control purpose or positional assessment - a technique known as Magnetic Resonance Navigation (MRN), but also for implementing a method of communication with intelligent microrobots. For untethered sensory microrobots having some level of intelligence and operating inside the body, the transmission power necessary to communicate information to an external computer via known methods is insufficient. In this work, a technique is described where such loss of transmission power due to the scaling of these microrobots can be compensated by the same MRI scanner acting as a more sensitive receiver. A communication scheme is implemented in the form of a frequency alteration in the electrical current circulating along a miniature coil embedded in a microrobot. The frequency of the electrical current could be regulated from a predetermined sensory threshold input implemented on the microrobot. Such a frequency provides information on the level of sensory information gathered by the microrobot, and it is determined using MR imaging. The proposed method is independent of the microrobot's position and orientation and can be extended to a larger number of microrobots for monitoring and mapping specific physiological conditions inside a larger region at any depths within the body

Conception et fabrication d'un microrobot sans fil autonome opérant dans un milieu aqueux

RÉSUMÉ Il existe plusieurs définitions du mot « robot ». L’une d’elles définit un robot comme un dispositif qui peut se déplacer et réagir à une excitation pour exécuter une ou plusieurs tâches dédiées. Un tel robot est pourvu d’une certaine forme d’intelligence ou d’un programme qui exécute ces tâches automatiquement sans l’intervention humaine. De plus, sa conception sera influencée par l’environnement dans lequel il évolue et par les fonctions qui doivent lui être intégrées pour effectuer des tâches prédéfinies. En microrobotique, le principal obstacle dans la miniaturisation des robots intelligents sans fil est d’obtenir la source de puissance nécessaire pour supporter les quatre fonctions de base (intelligence, détection, communication, actuation ou déplacement), malgré les contraintes d’espace. Deux approches principales peuvent être envisagées pour réduire les dimensions du robot, soit l’augmentation de la capacité de réception et de conversion énergétique, soit la diminution du besoin en énergie électrique.----------ABSTRACT There are several definitions of the word “robot”. One of them defines a robot as a device which can move and react to a stimulus to execute one or more dedicated tasks. Such a robot is endowed with a certain form of intelligence or a program which executes automatically without human intervention. Moreover, the design of a robot will be influenced by the environment in which it moves and by the functions which must be integrated to carry out some preset tasks. In microrobotics, a major difficulty during the miniaturization of intelligent wireless robots is to feed them with power to support the four basic functions (intelligence, sensors, communication, actuation or displacement) while meeting volume constraints. Therefore, two principal approaches can be considered to reduce the robot dimensions. The first would be to increase the reception capacity and energy conversion. The second would be to decrease the electrical power requirements

Hybrid bio-robotics: from the nanoscale to the macroscale

[eng] Hybrid bio-robotics is a discipline that aims at integrating biological entities with synthetic materials to incorporate features from biological systems that have been optimized through millions of years of evolution and are difficult to replicate in current robotic systems. We can find examples of this integration at the nanoscale, in the field of catalytic nano- and micromotors, which are particles able to self-propel due to catalytic reactions happening in their surface. By using enzymes, these nanomotors can achieve motion in a biocompatible manner, finding their main applications in active drug delivery. At the microscale, we can find single-cell bio-swimmers that use the motion capabilities of organisms like bacteria or spermatozoa to transport microparticles or microtubes for targeted therapeutics or bio-film removal. At the macroscale, cardiac or skeletal muscle tissue are used to power small robotic devices that can perform simple actions like crawling, swimming, or gripping, due to the contractions of the muscle cells. This dissertation covers several aspects of these kinds of devices from the nanoscale to the macro-scale, focusing on enzymatically propelled nano- and micromotors and skeletal muscle tissue bio-actuators and bio-robots. On the field of enzymatic nanomotors, there is a need for a better description of their dynamics that, consequently, might help understand their motion mechanisms. Here, we focus on several examples of nano- and micromotors that show complex dynamics and we propose different strategies to analyze their motion. We develop a theoretical framework for the particular case of enzymatic motors with exponentially decreasing speed, which break the assumptions of constant speed of current methods of analysis and need different strategies to characterize their motion. Finally, we consider the case of enzymatic nanomotors moving in complex biological matrices, such as hyaluronic acid, and we study their interactions and the effects of the catalytic reaction using dynamic light scattering, showing that nanomotors with negative surface charge and urease-powered motion present enhanced parameters of diffusion in hyaluronic acid. Moving towards muscle-based robotics, we investigate the application of 3D bioprinting for the bioengineering of skeletal muscle tissue. We demonstrate that this technique can yield well-aligned and functional muscle fibers that can be stimulated with electric pulses. Moreover, we develop and apply a novel co-axial approach to obtain thin and individual muscle fibers that resemble the bundle-like organization of native skeletal muscle tissue. We further exploit the versatility of this technique to print several types of materials in the same process and we fabricate bio-actuators based on skeletal muscle tissue with two soft posts. Due to the deflection of these cantilevers when the tissue contracts upon stimulation, we can measure the generated forces, therefore obtaining a force measurement platform that could be useful for muscle development studies or drug testing. With these applications in mind, we study the adaptability of muscle tissue after applying various exercise protocols based on different stimulation frequencies and different post stiffness, finding an increase of the force generation, especially at medium frequencies, that resembles the response of native tissue. Moreover, we adapt the force measurement platform to be used with human-derived myoblasts and we bioengineer two models of young and aged muscle tissue that could be used for drug testing purposes. As a proof of concept, we analyze the effects of a cosmetic peptide ingredient under development, focusing on the kinematics of high stimulation contractions. Finally, we present the fabrication of a muscle-based bio-robot able to swim by inertial strokes in a liquid interface and a nanocomposite-laden bio-robot that can crawl on a surface. The first bio-robot is thoroughly characterized through mechanical simulations, allowing us to optimize the skeleton, based on a serpentine or spring-like structure. Moreover, we compare the motion of symmetric and asymmetric designs, demonstrating that, although symmetric bio-robots can achieve some motion due to spontaneous symmetry breaking during its self-assembly, asymmetric bio-robots are faster and more consistent in their directionality. The nanocomposite-laden crawling bio-robot consisted of embedded piezoelectric boron nitride nanotubes that improved the differentiation of the muscle tissue due to a feedback loop of piezoelectric effect activated by the same spontaneous contractions of the tissue. We find that bio-robots with those nanocomposites achieve faster motion and stronger force outputs, demonstrating the beneficial effects in their differentiation. This research presented in this thesis contributes to the development of the field of bio-hybrid robotic devices. On enzymatically propelled nano- and micromotors, the novel theoretical framework and the results regarding the interaction of nanomotors with complex media might offer useful fundamental knowledge for future biomedical applications of these systems. The bioengineering approaches developed to fabricate murine- or human-based bio-actuators might find applications in drug screening or to model heterogeneous muscle diseases in biomedicine using the patient’s own cells. Finally, the fabrication of bio-hybrid swimmers and nanocomposite crawlers will help understand and improve the swimming motion of these devices, as well as pave the way towards the use of nanocomposite to enhance the performance of future actuators.[spa] La bio-robótica híbrida es una disciplina cuyo objetivo es la integración de entidades biológicas con materiales sintéticos para superar los desafíos existentes en el campo de la robótica blanda, incorporando características de los sistemas biológicos que han sido optimizadas durante millones de años de evolución natural y no son fáciles de reproducir artificialmente. Esta tesis cubre varios aspectos de este tipo de dispositivos desde la nanoescala a la macroescala, enfocándose en nano- y micromotores propulsados enzimáticamente y bio-actuadores y bio-robots basados en tejido muscular esquelético. En el campo de nanomotores enzimáticos, existe la necesidad de encontrar mejores modelos que puedan describir la dinámica de su movimiento para llegar a entender sus mecanismos de propulsión subyacentes. Aquí, nos enfocamos en diversos ejemplos de nano- y micromotores que muestran dinámicas de movimiento complejas y proponemos diferentes estrategias que se pueden utilizar para analizar y caracterizar este movimiento. Moviéndonos hacia robots basados en células musculares, investigamos la aplicación de la técnica de bioimpresión en 3D para la biofabricación de músculo esquelético. Demostramos que esta técnica puede producir fibras musculares funcionales y bien alineadas que puede ser estimuladas y contraerse con pulsos eléctricos. Investigamos la versatilidad de esta técnica para imprimir varios tipos de materiales en el mismo proceso y fabricamos bio-actuadores basados en músculo esquelético. Debido a los movimientos de unos postes gracias a las contracciones musculares, podemos obtener medidas de la fuerza ejercida, obteniendo una plataforma de medición de fuerzas que podría ser de utilidad para estudios sobre el desarrollo del músculo o para testeo de fármacos. Finalmente, presentamos la fabricación de un bio-robot basado en músculo esquelético capaz de nadar en la superficie de un líquido y un bio-robot con nanocompuestos incrustados que puede arrastrarse por una superficie sólida. El primer de ellos es minuciosamente caracterizado a través de simulaciones mecánicas, permitiéndonos optimizar su esqueleto, basado en una estructura tipo serpentina o muelle. El segundo bio-robot contiene nanotubos piezoeléctricos incrustados en su tejido, los cuales ayudan en la diferenciación del músculo debido a una retroalimentación basada en su efecto piezoeléctrico y activada por las contracciones espontáneas del tejido. Mostramos que estos bio-robots pueden generar un movimiento más rápido y una mayor generación de fuerza, demostrando los efectos beneficiales en la diferenciación del tejido

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018