Control of magnetotactic bacterium in a micro-fabricated maze

We demonstrate the closed-loop control of a magnetotactic bacterium (MTB), i.e., Magnetospirillum magnetotacticum, within a micro-fabricated maze using a magneticbased manipulation system. The effect of the channel wall on the motion of the MTB is experimentally analyzed. This analysis is done by comparing the characteristics of the transient- and steady-states of the controlled MTB inside and outside a microfabricated maze. In this analysis, the magnetic dipole moment of our MTB is characterized using a motile technique (the u-turn technique), then used in the realization of a closed-loop control system. This control system allows the MTB to reach reference positions within a micro-fabricated maze with a channel width of 10 μm, at a velocity of 8 μm/s. Further, the control system positions the MTB within a region-of-convergence of 10 μm in diameter. Due to the effect of the channel wall, we observe that the velocity and the positioning accuracy of the MTB are decreased and increased by 71% and 44%, respectively

Planar manipulation of magneto-tactic bacteria using unidirectional magnetic fields

We show for the first time that an alternating unidirectional magnetic field generated by a magnetic erase head allows planar manipulation of magneto-tactic bacteria (MTB), and is not restricted to parallel directions only. We used squared-shaped magnetic fields of approximately 4 mT while sweeping from 0.25 to 10 Hz, and found that at frequencies of over 3 Hz the mean orthogonal velocity becomes constant. The erase head offers a significant reduction in size and complexity over conventional manipulators

The behaviour of magnetotactic bacteria in changing magnetic fields

Die Beobachtung des Verhaltens von magnetotaktischen Bakterien (MTB) in wechselndeMagnetfeldern kann signifikante direkte und indirekte Informationen offenlegen über deren Merkmale und physiologische Eigenschaften. Sowohl Einzel- als auchMassenanalyse wurden in der vorliegenden Studie durchgeführt. Die Einzelzell-Experimente wurden in einem mikrofluidischen Chip mitmaßgefertigtem Design durchgeführt, in welchem die MTB fokussiert werden konnten während einMagnetfeld mittels eines permanentenMagneten angelegt wurde, welcher unter demMikroskoptisch befestigt war. Beobachtungen und Aufnahme der Reaktionen erlaubte eine offline-Analyse der Bewegungsbahnen. Diese Auswertung zeigte, dass die Zellen unterschiedlich reagierten auf Variation derMagnitude derMagnetfeldstärke. DesWeiteren konnte durch Simulationen und Experimente aufgezeigt werden, dass der Widerstand der MTB unterschätzt wurde, was zu zusätzlichen makroskopische Experimenten führte, um eine Verbindung von morphologischer Eigenschaften und Rotationswiderstandsprofilen darzulegen. Diese Experimente wurden durchgeführt in einem Gefäßmit Silikonöl unter Verwendung verschiedener 3D-gedruckter Modelle von verschiedenen ellipsoid- und spirillum-basierenden Morphologien. Die Modelle begründeten sich auf Elektronenmikroskop-Abbildungen von tatsächlichen MTB. Die Auswertung dieser Experimente konnte zur Aufklärung beitragen, dass Eigenschaften der MTB nicht in existierende Modelle des Rotationswiderstandes berücksichtigt werden. Die Massenanalyse wurde durchgeführt in einem maßangefertigtem Optischen-Dichte-Messer, spezifisch hergestellt umMagnetfeld-Orientierungen mit Photospektrometrie zu kombinieren. Von diesen Beobachtungen konnte der magnetische Gehalt von einer MTB-Kultur und Einzelproben abgeleitet werden, sowohl absolut als auch relativ. Zusätzlich wurde die Reaktionszeit einer verwendeten Charge gemessen werden umdenmagnetischen dipol-Moment mit dem Rotationswiderstand zu korrelieren. Dies erlaubte eine Unterscheidung zwischen verschiedenen Qualitäten und Quantitäten von Kulturen, als auch Langzeit- und kontinuierliche Beobachtung desWachstumsverhaltens von diesen. Trotz des Auffindens neuer Eigenschaften durch welche eine genauere Berechnung von Rotationswiderstandsprofilen möglich wurde bleibt die Länge eines Objekts weiterhin der dominierende Faktor im Zusammenspiel von magnetischem Drehmoment und Rotationswiderstandskraft. UnserModell erlaubt eine genauere Vorhersage des Rotationswiderstandes von Objekten mit ähnlichen Formen wie MTB in Schleichender Strömung als auch Zuständen von geringen Reynoldszahlen.The observation of behaviour of magnetotactic bacteria (MTB) in changing magnetic fields can give significant direct and indirect information about their traits and biophysical properties. Both single and bulk experiment and analysis were performed in this study. The single cel experimentswere performed inside custommicrofluidic chips designed to keep the MTB in focus, while a magnet field was applied using a permanent magnet mounted under a microscope stage. Observation and recording of the response allowed for off-line analysis of the trajectories. This analysis has shown that the cells respond differently to varyingmagnitudes of magnetic field strength. Furthermore, from simulations and experiments we have found that the drag of the MTB had been underestimated, which lead to additional macroscopic experiments relating morphological traits to more rotational drag profiles. These experiments were done in a vat of silicone oil using 3D-printed models of varying spheroid- and spirillum-based morphologies. The models were based on scanning electron microscope images of actualMTB. Analysis of these experiments elucidated the contribution of traits not included in existing models for rotational drag. The bulk analysis was performed in a custom made optical density meter, specifically designed to combine magnetic field orientations with photo spectrometry. From our observation we could derive the magnetic response, both absolute and relative, of a given culture or sample of MTB. Additionally, the response time of a given batch could also be measured, relating the magnetic dipole moment with the rotational drag. This allowed distinguishing between different quality and quantity of cultures, as well as long termand continuous observation of a culture in growth. In spite of having found new traits by which one can more accurately calculate the rotational drag profile, the length of an object still remains the dominate factor when balancing magnetic torque and drag force. Our model does allow for predicting more accurately the rotational drag of objects with shapes similar toMTB in Stokes flow or under low Reynolds number conditions

Études des configurations spatio-temporelles du champ magnétique sur le contrôle des bactéries magnétotactiques

Depuis que les scientifiques se sont intéressés à travailler à l’échelle nano et micro, la création de véhicules qui puissent y travailler est devenue une nécessité. Ces véhicules sont des nano-micro robots qui doivent fonctionner dans ces milieux de manière autonome et contrôlée. L’une des plus grandes utilités de ces nano-micro robots, par exemple, est leur utilisation dans un système microvasculaire pour transporter des agents thérapeutiques vers les tumeurs cancéreuses de façon contrôlée. La technologie de fabrication des robots artificiels actuelle n’est pas en mesure de fournir ce nano-micro robot. Pour contourner cette limitation, nous avons choisi un micro robot déjà existant dans la nature. C’est la bactérie magnétotactique Magnetococcus Marinus souche MC-1, d’une taille de 2 µm de diamètre et ayant : 1) une autonomie de mouvement grâce à son propre système de propulsion fourni par deux moteurs moléculaires (flagelles), 2) une chaîne de particules nanométriques magnétiques (magnétosomes), qui permet à la bactérie de s’aligner avec le champ magnétique et de se propulser dans la direction du champ. En plus, les microrobots ont la capacité de réaliser des tâches dans l’environnement micrométrique comme : la microfabrication et le transport. L’équipe du laboratoire NanoRobotique de Polytechnique de Montréal a développé une plateforme de contrôle des bactéries magnétiques dans le but de contrôler leurs déplacements dans un système in vivo, et ainsi de transporter des agents thérapeutiques directement dans le cancer. Autrement dit, cette nouvelle plateforme permet de guider la bactérie magnétotactique vers une cible prédéfinie. L’objectif de ce mémoire de recherche est d’améliorer la modélisation du champ magnétique de cette plateforme. Cette nouvelle modélisation permettra de réduire les durées d’agrégation et de déplacement des bactéries magnétiques tout en augmentant la performance de la plateforme. D’abord, une méthode de contrôle basée sur la géométrie spatiale du champ magnétique a été développée et validée. Finalement, une étude de comportement des bactéries magnétiques exposées au champ magnétique alternatif a été effectuée afin de pouvoir développer une technique novatrice de contrôle.----------ABSTRACT Working at the nano and micro scale environment has provided scientists with an immense opportunity to explore within small and previously unreachable areas. Evidently, creation of vehicles that could facilitate such careful maneuver has gained a lot of interest. These vehicles are nanomicrorobots that perform autonomously under controlled environment. Among many research disciplines that could advance with such miniature system, drug delivery and navigation is one of the most beneficial uses for these controlled nanomicrorobots; acting as therapeutic agent carriers targeting cancerous tumors by traveling through complex microvascular structures. Current artificial robot technology lacks maturity in manufacturing mass scale nanomicrorobots. Therefore, inspired by nature, we chose special bacteria bona fide to serve as microrobots. Magnetotactic Magnetococcus Marinus strain MC-1 has: 1) an autonomy movement with its own propulsion system provided by two molecular motors (flagella) and 2) a chain of magnetic nanoparticles (magnetosomes) acting as a compass that aligns the moving bacteria in the direction of external magnetic field. These 2 µm diameter bacteria have the ability to perform as actuators, micro-fabricators and transporters. Polytechnique NanoRobotics Montreal laboratory team has developed a magnetic controller platform to control these bacteria in vivo and deliver therapeutic agents directly into the cancer tissue. In other words, this platform helps navigate the magnetotactic bacteria to the predefined target. The objective of this research thesis is to improve the magnetic field modeling of this platform. Our new proposed model will reduce the bacteria displacement and aggregation time while increasing the performance of the platform. At the beginning, a control method based on the spatial configuration of the magnetic field has been developed and validated. And at the end, a study on magnetic bacteria behavior exposed to alternating magnetic field is performed in order to develop an innovative control technique

Characterization and Control of Biological Microrobots

This work addresses the characterization and control of Magnetotactic Bacterium (MTB) which can be considered as a biological microrobot. Magnetic dipole moment of the MTB and response to a field-with-alternating-direction are characterized. First, the magnetic dipole moment is characterized using four tech-niques, i.e., Transmission Electron Microscope images, flip-time, rotating-field and u-turn techniques. This characterization results in an average magnetic dipole mo-ment of 3.32×10−16 A.m2 and 3.72×10−16 A.m2 for non-motile and motile MTB, respectively. Second, the frequency response analysis of MTB shows that its ve-locity decreases by 38% for a field-with-alternating-direction of 30 rad/s. Based on the characterized magnetic dipole moment, the magnetic force produced by our magnetic system is five orders-of-magnitude less than the propulsion force gener-ated by the flagellum of the MTB. Therefore, point-to-point positioning of MTB cannot be achieved by exerting a magnetic force. A closed-loop control strategy is devised based on calculating the position tracking error, and capitalizes on the fre-quency response analysis of the MTB. Point-to-point closed-loop control of MTB is achieved for a reference set-point of 60 mm with average velocity of 20 mm/s. The closed-loop control system positions the MTB within a region-of-convergence of 10 mm diameter