Thrifty swimming with shear-thinning

Microscale propulsion is integral to numerous biomedical systems, for example biofilm formation and human reproduction, where the surrounding fluids comprise suspensions of polymers. These polymers endow the fluid with non-Newtonian rheological properties, such as shear-thinning and viscoelasticity. Thus, the complex dynamics of non-Newtonian fluids presents numerous modelling challenges, strongly motivating experimental study. Here, we demonstrate that failing to account for "out-of-plane" effects when analysing experimental data of undulatory swimming through a shear-thinning fluid results in a significant overestimate of fluid viscosity around the model swimmer C. elegans. This miscalculation of viscosity corresponds with an overestimate of the power the swimmer expends, a key biophysical quantity important for understanding the internal mechanics of the swimmer. As experimental flow tracking techniques improve, accurate experimental estimates of power consumption using this technique will arise in similar undulatory systems, such as the planar beating of human sperm through cervical mucus, will be required to probe the interaction between internal power generation, fluid rheology, and the resulting waveform

A Scalable Strategy for Open Loop Magnetic Control of Microrobots Using Critical Points

A novel scalable strategy for open loop control of ferromagnetic microrobots on a plane using a scalable array of electromagnets is presented. Instead of controlling the microrobot directly, we create equilibrium points in the magnetic force field that are stable and attractive on the plane in which the microrobot is to be controlled. The microrobot moves into these equilibrium points rapidly in presence of low viscous forces, and thus controlling the equilibrium points let us control the microrobot precisely. An unit/cell in the array of electromagnets allows precise control of the microrobot in the unit/cell’s domain. Motion synthesis across multiple overlapping domains allows control of the microrobot in large regions across the array. We perform numerical analysis and demonstrate the control of the ferromagnetic microrobot using the proposed method through simulations

MicroBioRobots for Single Cell Manipulation

One of the great challenges in nano and micro scale science and engineering is the independent manipulation of biological cells and small man-made objects with active sensing. For such biomedical applications as single cell manipulation, telemetry, and localized targeted delivery of chemicals, it is important to fabricate microstructures that can be powered and controlled without a tether in fluidic environments. These microstructures can be used to develop microrobots that have the potential to make existing therapeutic and diagnostic procedures less invasive. Actuation can be realized using various different organic and inorganic methods. Previous studies explored different forms of actuation and control with microorganisms. Bacteria, in particular, offer several advantages as controllable micro actuators: they draw chemical energy directly from their environment, they are genetically modifiable, and they are scalable and configurable in the sense that any number of bacteria can be selectively patterned. Additionally, the study of bacteria inspires inorganic schemes of actuation and control. For these reasons, we chose to employ bacteria while controlling their motility using optical and electrical stimuli. In the first part of the thesis, we demonstrate a bio-integrated approach by introducing MicroBioRobots (MBRs). MBRs are negative photosensitive epoxy (SU8) microfabricated structures with typical feature sizes ranging from 1-100 μm coated with a monolayer of the swarming Serratia marcescens. The adherent bacterial cells naturally coordinate to propel the microstructures in fluidic environments, which we call Self-Actuation. First, we demonstrate the control of MBRs using self-actuation, DC electric fields and ultra-violet radiation and develop an experimentally-validated mathematical model for the MBRs. This model allows us to to steer the MBR to any position and orientation in a planar micro channel using visual feedback and an inverted microscope. Examples of sub-micron scale transport and assembly as well as computer-based closed-loop control of MBRs are presented. We demonstrate experimentally that vision-based feedback control allows a four-electrode experimental device to steer MBRs along arbitrary paths with micrometer precision. At each time instant, the system identifies the current location of the robot, a control algorithm determines the power supply voltages that will move the charged robot from its current location toward its next desired position, and the necessary electric field is then created. Second, we develop biosensors for the MBRs. Microscopic devices with sensing capabilities could significantly improve single cell analysis, especially in high-resolution detection of patterns of chemicals released from cells in vitro. Two different types of sensing mechanisms are employed. The first method is based on harnessing bacterial power, and in the second method we use genetically engineered bacteria. The small size of the devices gives them access to individual cells, and their large numbers permit simultaneous monitoring of many cells. In the second part, we describe the construction and operation of truly micron-sized, biocompatible ferromagnetic micro transporters driven by external magnetic fields capable of exerting forces at the pico Newton scale. We develop micro transporters using a simple, single step micro fabrication technique that allows us to produce large numbers in the same step. We also fabricate microgels to deliver drugs. We demonstrate that the micro transporters can be navigated to separate single cells with micron-size precision and localize microgels without disturbing the local environment

Actuation, Sensing And Control For Micro Bio Robots

The continuing trend in miniaturization of technology, advancements in micro and nanofabrication and improvements in high-resolution imaging has enabled micro- and meso-scale robots that have many applications. They can be used for micro-assembly, directed drug delivery, microsurgery and high-resolution measurement. In order to create microrobots, microscopic sensors, actuators and controllers are needed. Unique challenges arise when building microscale robots. For inspiration, we look toward highly capable biological organisms, which excel at these length scales. In this dissertation we develop technologies that combine biological components and synthetic components to create actuation, sensing and assembly onboard microrobots. For actuation, we study the dynamics of synthetic micro structures that have been integrated with single-cell biological organisms to provide un-tethered onboard propulsion to the microrobot. For sensing, we integrate synthetically engineered sensor cells to enable a system capable of detecting a change in the local environment, then storing and reporting the information. Furthermore, we develop a bottom-up fabrication method using a macroscopic magnetic robot to direct the assembly of inorganic engineered micro structures. We showcase the capability of this assembly method by demonstrating highly-specified, predictable assembly of microscale building blocks in a semi-autonomous experiment. These magnetic robots can be used to program the assembly of passive building blocks, with the building blocks themselves having the potential to be arbitrarily complex. We extend the magnetic robot actuation work to consider control algorithms for multiple robots by exploiting spatial gradients of magnetic fields. This thesis makes contributions toward actuation, sensing and control of autonomous micro systems and provides technologies that will lead to the development of swarms of microrobots with a suite of manipulation and sensing capabilities working together to sense and modify the environment

Therapeutic Magnetic Microcarriers Characterization by Measuring Magnetophoretic Attributes

RÉSUMÉ Des micro/nano-robots sont considérés comme une approche prometteuse pour mener des interventions minimalement invasives. Nous avons proposé d'intégrer des nanoparticules magnétiques dans des agents thérapeutiques ou de diagnostic afin de les contrôler magnétiquement. Un scanner d’imagerie par résonance magnétique (IRM) clinique modifié est utilisé afin de fournir la force motrice qui permet à ces microporteurs magnétiques à naviguer dans le réseau vasculaire humain. En utilisant des séquences spécifiques des gradients de résonance magnétique (MR) cette méthode a été validée dans des travaux de recherche antérieurs. Magnétophorèse est le terme utilisé pour décrire le fait qu'une particule magnétique modifie sa trajectoire sous l'influence d'une force magnétique tout en étant portée par un flux de fluide. Ce mouvement dépend des caractéristiques de la particule magnétique, de sa forme géométrique, des attributs de l'écoulement de fluide et d'autres facteurs. Dans notre méthode proposée, les microporteurs magnétiques peuvent être réalisés de différentes manières, et donc leur réponse sera différente à la même force magnétique et dans les mêmes conditions d'écoulement de fluide. Le résultat du traitement thérapeutique utilisant notre méthode dépend de la sélection adéquate des agents thérapeutiques et/ou de diagnostic à utiliser. Le microporteur magnétique thérapeutique et /ou de diagnostic choisi influe également sur le choix de la séquence des gradients magnétiques que meilleur se ajustement pour un traitement donné. Ce mémoire de maîtrise présente la conception d'un dispositif destiné à évaluer les propriétés magnétophorétiques des agents microporteurs magnétiques thérapeutiques et/ou de diagnostic. Une telle caractérisation est essentielle pour déterminer les séquences optimales des gradients magnétiques pour dévier leur trajectoire à travers des réseaux vasculaires relativement complexes dans le but d'atteindre un objectif prédéfini. Un dispositif microfluidique est fabriqué pour valider la conception. Las vitesses magnétophorétiques sont mesurées et une méthode de suivi simple est proposée. Les résultats des experiences préliminaires indiquent que, malgré certaines limitations, la technique proposée a le potentiel d’être approprié pour caractériser n'importe quel microporteur magnétique thérapeutique et/ou de diagnostic contenant différents taux de nanoparticules magnétiques.----------ABSTRACT Micro/nano robots are considered a promising approach to conduct minimally invasive interventions. We have proposed to embed magnetic nanoparticles in therapeutic or diagnostic agents in order to magnetically control them. A modified clinical Magnetic Resonance Imaging (MRI) scanner is used to provide the driving force that allows these magnetically embedded microcarriers to navigate the vascular human network. By using specific Magnetic Resonance (MR) gradient sequences this method has been validated in previous research works. Magnetophoresis is the term used to describe the fact that a magnetic particle changes its trajectory under the influence of a magnetic force while being carried by a fluid flow. This movement depends on the particle’s magnetic characteristics, the particle’s geometric shape, the fluid flow’s attributes and other factors. In our proposed method, magnetic microcarriers can be produced in several different ways, and so their response will differ to the same magnetic force and fluid flow conditions. The outcome of the therapeutic treatment using our method depends on the adequate selection of the therapeutic and/or diagnosis agents to be used. The selected therapeutic and/or diagnosis magnetic microcarrier also influences the selection of the MR gradient sequence that best fit for a given treatment. This master’s thesis presents the design of a device intended to assess the magnetophoretic properties of magnetic therapeutic microcarriers and/or diagnostic agents. Such characterization is essential for determining the optimal sequences of magnetic gradients to deflect their trajectory through relatively complex vascular networks in order to reach a pre-defined target. A microfluidic device was fabricated to validate the design. Magnetophoretic velocities are measured and a simple tracking method is proposed. The preliminary experimental results indicate that, despite some limitations, the proposed technique has the potential to be appropriate to characterize any drug and/or diagnosis magnetic microcarrier containing different magnetic nanoparticle content

Capturing, Analyzing and Collecting Adherent Cells Using Microarray Technologies

Effective separation of a particular cell of interest from a heterogeneous cell population is crucial to many areas of biomedical research including microscopy, clinical diagnostics and stem cell studies. Examples of such studies include the analysis of single cells, isolation of transfected cells and cell transformation studies. Biological technologies can have skewed results if cells outside of the type of interest are present. Additionally, in many instances the targeted cells are of low abundance with respect to the heterogeneous population. For these reasons, it is important to have a technique capable of identifying the desired cells, separating these cells from unwanted cells and collecting the marked cells for further analysis. Two biotools, referred to as micropallets and microrafts, have recently been introduced for sorting adherent cells. These devices comprise arrays of microelements weakly attached to a substrate. Following culture of adherent cells on the elements, individual microstructures are selectively detached from the array while still carrying the cells. These technologies have shown success in sorting single cells from small heterogeneous cell populations with high post sorting viabilities. However, previous device designs employed gravity-based collection methods and small microelement arrays which substantially reduced the collection yields, purities and sample sizes. In this dissertation new approaches are described for capturing, examining and isolating individual cells by micropallet and microraft technologies. Initially a new approach was developed to isolate released microstructures from the array employing magnetism. Microstructures were embedded with uniformly dispersed magnetic nanoparticles which allowed collection by an external magnet immediately following release. Application of a magnetic field permitted microstructure collection with high yield, precision and purity. This improved collection efficiency enabled isolation of very rare cell types. Large arrays constituting over 106 micropallets were developed along with imaging analysis software to identify and sort low abundance target cells. This system was employed to isolate breast cancer stem cells from a heterogeneous cell population and circulating tumor cells directly from peripheral blood. Additionally, an array-based cell colony replication strategy was established which allowed highly efficient colony splitting and sampling.Doctor of Philosoph

Modeling, Control, and Experimental Characterization of Microbiorobots

In this paper, we describe how motile microorganisms can be integrated with engineered microstructures to develop a micro-bio-robotic system. SU-8 microstructures blotted with swarmer cells of Serratia Marcescens in a monolayer are propelled by the bacteria in the absence of any environmental stimulus. We call such microstructures with bacteria MicroBioRobots (MBRs) and the uncontrolled motion in the absence of stimuli self actuation. Our paper has two primary contributions. First, we demonstrate the control of MBRs using self actuation and DC electric fields, and develop an experimentally validated mathematical model for the MBRs. This model allows us to use self actuation and electrokinetic actuation to steer the MBR to any position and orientation in a planar micro channel. Second, we combine our experimental setup and a feedback control algorithm to steer robots with micrometer accuracy in two spatial dimensions. We describe the fabrication process for MBRs and show experimental results demonstrating actuation and control