Magnetic Response of Magnetospirillum Gryphiswaldense

In this study we modelled and measured the U-turn trajectories of individual magnetotactic bacteria under the application of rotating magnetic fields, ranging in ampitude from 1 to 12 mT. The model is based on the balance between rotational drag and magnetic torque. For accurate verification of this model, bacteria were observed inside 5 m tall microfluidic channels, so that they remained in focus during the entire trajectory. From the analysis of hundreds of trajectories and accurate measurements of bacteria and magnetosome chain dimensions, we confirmed that the model is correct within measurement error. The resulting average rate of rotation of Magnetospirillum Gryphiswaldense is 0.74 +- 0.03 rad/mTs.Comment: 17 pages, 12 figure

Scalable strategies for tumour targeting of magnetic carriers and seeds

With the evolving landscape of medical oncology, focus has shifted away from nonspecific cytotoxic treatment strategies toward therapeutic paradigms more characteristic of targeted therapies. These therapies rely on delivery vehicles such as nano-carriers or micro robotic devices to boosts the concentration of therapeutics in a specific targeted site inside the body. The use of externally applied magnetic field is suggested to be a predominant approach for remote localisation of magnetically responsive carriers and devices to the target region that could not be otherwise reached. However, the fast decline of the magnetic fields and gradients with increasing distances from the source is posing a major challenge for its clinical application. The aim of this thesis was to investigate potential magnetic delivery strategies which can circumvent some of the typical limitations of this technique. Two different approaches were explored to this end. The first approach was to characterise the ability of a conventional permanent magnet on targeting individual nano-carriers and develop novel magnetic designs which improve the targeting efficiency. The second approach was evaluating the feasibility of a magnetic resonance imaging system to move a millimetre-sized magnetic particle within the body. Phantom and in vivo magnetic targeting experiments illustrated the significant increase in effective targeting depth when our novel magnetic design was used for targeting nano-carriers compared with conventional magnets. In the later part of the thesis, the proof of concept and characterisation experiments showed that a 3 mm magnetic particle can be moved in ex vivo brain tissue using a magnetic resonance imaging system using clinically relevant gradient strengths. The magnetic systems introduced in this thesis provide the potential to target nano-carriers and millimetre-sized thermoseeds to tumours located at deep regions of human body through vasculature and soft tissue respectively

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

Study and development of a magnetic steering system for microrobots

In a close future micro-scaled untethered robots might be able to access small spaces inside the human body, currently reachable only by using invasive surgical methods, thus revolutionizing future medicine. The aim of this Master Thesis work is to study and develop a system that can exploit static magnetic fields and gradients to steer purpose-developed microrobots. A concept of the device for the generation of magnetic fields is first elaborated, moving from the state-of-art systems based on Helmholtz and Maxwell coils, which can generate, respectively, nearly uniform magnetic fields and gradients. A uniform magnetic field can be used to orient a magnetic or magnetisable object, aligning it with the direction of the field, while a uniform magnetic gradient can be used to shift such an object. The developed system is formed by two coils in the Maxwell geometrical configuration and independently powered in order to generate a uniform magnetic gradient, a quasi-uniform magnetic field or a superimposition of the two, reducing the overall complexity of the hardware with respect to the systems also employing Helmholtz coils. An analytical model of the on-axis magnetic field generated by the device and a finite element model of the field in the workspace are developed. Three microrobot prototypes are then considered: a millimetre-sized NdFeB cylindrical permanent magnet, which allows to test the maximum performances of the developed device, a polymeric microbead, which is more compatible with biomedical applications but less reactive to magnetic fields than a permanent magnet, and a polymeric nanofilm, which allows to test the steering of very anisotropic shapes, both containing iron oxide nanoparticles. Models of their interaction with magnetic fields are presented. Furthermore, a model of the motion of the three prototypes employing the developed magnetic device is presented. The experimental set up is described, including the two coils and their support backing, the monitoring and powering circuitry and a software kit containing four graphical user interfaces for the calibration and validation of the system. After a set of trials performed for the calibration of the magnetic-field-generating device, the system is tested in steering the microrobot prototypes. The extrapolated data are compared to the behaviours predicted by the magnetic motion models. The abilities of the magnetic steering system and its main limits are finally examined, suggesting possible improvements of both the magnetic device and the microrobots in order to enhance their control and manipulation. In particular indications for developing the next-generation of wireless magnetically-actuated microrobots and the relative steering systems are extrapolated

Custom-Designed Biohybrid Micromotor for Potential Disease Treatment

Micromotors are recognized as promising candidates for untethered micromanipulation and targeted cargo transport. Their future application is, however, hindered by the low efficiency of drug encapsulation and their poor adaptability in physiological conditions. To address these challenges, one potential solution is to incorporate micromotors with biological materials as the combination of functional biological entities and smart artificial parts represents a manipulable and biologically friendly approach. This dissertation focuses on the development of custom-designed micromotors combined with sperm and their potential applications on targeted diseases treatment. By means of 2D and 3D lithography methods, microstructures with complex configurations can be fabricated for specific demands. Bovine and human sperm are both for the first time explored as drug carriers thanks to their high encapsulation efficiency of hydrophilic drugs, their powerful self-propulsion and their improved drug-uptake relying on the somatic-cell fusion ability. The hybrid micromotors containing drug loaded sperm and constructed artificial enhancements can be self-propelled by the sperm flagella and remotely guided and released to the target at high precision by employing weak external magnetic fields. As a result, micromotors based on both bovine and human sperm show significant anticancer effect. The application here can be further broadened to other biological environments, in particular to the blood stream, showing the potential on the treatment of blood diseases like blood clotting. Finally, to enhance the treatment efficiency, in particular to control sperm number and drug dose, three strategies are demonstrated to transport swarms of sperm. This research paves the way for the precision medicine based on engineered sperm-based micromotors

Magnetic Drug Targeting: Developing the Basics

Focusing medicine to disease locations is a needed ability to treat a variety of pathologies. During chemotherapy, for example, typically less than 0.1% of the drugs are taken up by tumor cells, with the remaining 99.9% going into healthy tissue. Physicians often select the dosage by how much a patient can physically withstand rather than by how much is needed to kill all the tumor cells. The ability to actively position medicine, to physically direct and focus it to specific locations in the body, would allow better treatment of not only cancer but many other diseases. Magnetic drug targeting (MDT) harnesses therapeutics attached to magnetizable particles, directing them to disease locations using magnetic fields. Particles injected into the vasculature will circulate throughout the body as the applied magnetic field is used to attempt confinement at target locations. The goal is to use the reservoir of particles in the general circulation and target a specific location by pulling the nanoparticles using magnetic forces. This dissertation adds three main advancements to development of magnetic drug targeting. Chapter 2 develops a comprehensive ferrofluid transport model within any blood vessel and surrounding tissue under an applied magnetic field. Chapter 3 creates a ferrofluid mobility model to predict ferrofluid and drug concentrations within physiologically relevant tissue architectures established from human autopsy samples. Chapter 4 optimizes the applied magnetic fields within the particle mobility models to predict the best treatment scenarios for two classes of chemotherapies for treating future patients with hepatic metastatic breast cancer microtumors

OPTIMAL CONTROL OF OBJECTS ON THE MICRO- AND NANO-SCALE BY ELECTROKINETIC AND ELECTROMAGNETIC MANIPULATION: FOR BIO-SAMPLE PREPARATION, QUANTUM INFORMATION DEVICES AND MAGNETIC DRUG DELIVERY

In this thesis I show achievements for precision feedback control of objects inside micro-fluidic systems and for magnetically guided ferrofluids. Essentially, this is about doing flow control, but flow control on the microscale, and further even to nanoscale accuracy, to precisely and robustly manipulate micro and nano-objects (i.e. cells and quantum dots). Target applications include methods to miniaturize the operations of a biological laboratory (lab-on-a-chip), i.e. presenting pathogens to on-chip sensing cells or extracting cells from messy bio-samples such as saliva, urine, or blood; as well as non-biological applications such as deterministically placing quantum dots on photonic crystals to make multi-dot quantum information systems. The particles are steered by creating an electrokinetic fluid flow that carries all the particles from where they are to where they should be at each time step. The control loop comprises sensing, computation, and actuation to steer particles along trajectories. Particle locations are identified in real-time by an optical system and transferred to a control algorithm that then determines the electrode voltages necessary to create a flow field to carry all the particles to their next desired locations. The process repeats at the next time instant. I address following aspects of this technology. First I explain control and vision algorithms for steering single and multiple particles, and show extensions of these algorithms for steering in three dimensional (3D) spaces. Then I show algorithms for calculating power minimum paths for steering multiple particles in actuation constrained environments. With this microfluidic system I steer biological cells and nano particles (quantum dots) to nano meter precision. In the last part of the thesis I develop and experimentally demonstrate two dimensional (2D) manipulation of a single droplet of ferrofluid by feedback control of 4 external electromagnets, with a view towards enabling feedback control of magnetic drug delivery to reach deeper tumors in the long term. To this end, I developed and experimentally demonstrated an optimal control algorithm to effectively manipulate a single ferrofluid droplet by magnetic feedback control. This algorithm was explicitly designed to address the nonlinear and cross-coupled nature of dynamic magnetic actuation and to best exploit available electromagnetic forces for the applications of magnetic drug delivery

Artificial Muscles

Course material for "Artificial Muscles" e-course