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

Drug-Loaded IRONSperm clusters: modeling, wireless actuation, and ultrasound imaging

Individual biohybrid microrobots have the potential to perform biomedical in vivo tasks such as remote-controlled drug and cell delivery and minimally invasive surgery. This work demonstrates the formation of biohybrid sperm-templated clusters under the influence of an external magnetic field and essential functionalities for wireless actuation and drug delivery. Ferromagnetic nanoparticles are electrostatically assembled around dead sperm cells, and the resulting nanoparticle-coated cells are magnetically assembled into three-dimensional biohybrid clusters. The aim of this clustering is threefold: First, to enable rolling locomotion on a nearby solid boundary using a rotating magnetic field; second, to allow for noninvasive localization; third, to load the cells inside the cluster with drugs for targeted therapy. A magneto-hydrodynamic model captures the rotational response of the clusters in a viscous fluid, and predicts an upper bound for their step-out frequency, which is independent of their volume or aspect ratio. Below the step-out frequency, the rolling velocity of the clusters increases nonlinearly with their perimeter and actuation frequency. During rolling locomotion, the clusters are localized using ultrasound images at a relatively large distance, which makes these biohybrid clusters promising for deep-tissue applications. Finally, we show that the estimated drug load scales with the number of cells in the cluster and can be retained for more than 10 h. The aggregation of microrobots enables them to collectively roll in a predictable way in response to an external rotating magnetic field, and enhances ultrasound detectability and drug loading capacity compared to the individual microrobots. The favorable features of biohybrid microrobot clusters place emphasis on the importance of the investigation and development of collective microrobots and their potential for in vivo applications

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

Embedded Energy Landscapes In Soft Matter For Micro-Robotics And Reconfigurable Structures

The ability to manipulate microscale objects with precision to form complex structures is central to the field of micro-robotics and to the realization of reconfigurable systems. Understanding and exploiting the forces that dominate at the microscale in complex environments pose major challenges and open untapped opportunities. This is particularly the case for micro-particles in soft milieu like fluid interfaces or nematic liquid crystalline fluids, which deform or reorganize around dispersed colloids or near bounding surfaces. These energetically costly deformations can be designed as embedded energy landscapes, a form of physical intelligence, to dictate emergent colloidal interactions. The fluid nature of these soft milieu allows colloids to move to minimize the free energy and externally forced robotic structures to re-write the embedded energy landscapes in the domain. Such physically intelligent systems are of great interest at the intersection of materials science and micro-robotics. Micro-particles on fluid interfaces deform the interface shape, migrate, and assemble to minimize the capillary energy. In the first part of my thesis, I design and fabricate a magnetic micro-robot as a mobile curvature source to interact with passive colloids on the water/oil interface. An analytical expression that includes both capillary and hydrodynamic interactions is derived and captures the main feature of experimental observations. I further demonstrate multiple micro-robotic tasks including directed assembly, cargo carrying, desired release and cargo delivery on the interface. Micro-particles in confined nematic liquid crystals (NLCs) distort the nematic director field, generating interactions. These interactions depend strongly on the colloids shape and surface chemistry, geometric frustration of director field and behavior of dynamic topological defects. To probe far-from-equilibrium dynamics, I fabricate a magnetic disk with hybrid anchoring. Upon controlled rotation, the disk’s companion defect undergoes periodic rearrangement, executing a complex swim stroke that propels disk translation. I study this new swimming modality in both high and low Ericksen number regimes. At high rotation rates, the defect elongates significantly adjacent to the disk, generating broken symmetries that allow steering of the disk. This ability is exploited in path planning. Thereafter, I design a four-armed micro-robot as a mobile distortion source to promote passive colloids assembly at particular sites via emergent interactions in NLCs whose strengths are characterized and found to be several orders of magnitude larger than thermal energies. While the strength of theses interactions allows colloidal cargo to be carried with the micro-robot during translation, it poses challenges for cargo release. We find that rotation of this micro-robot generates a complex dynamic defect-sharing event with colloidal cargo that spurs cargo release. Thereafter, I demonstrate the ability to exploit NLC elastodynamics to construct reconfigurable colloidal structures in a micro-robotics platform. At the colloidal scale, rotation dynamics are easier to generate, and this motivated me to exploit the topological swimming modality of the micro-robot. Using programmable rotating fields to direct the micro-robot’s motion, I achieve fully autonomous cargo manipulations including approach, assembly, transport and release. The ability to dynamically manipulate micro-particles and their structures in soft matter systems with embedded energy landscapes, as demonstrated in this thesis, creates new possibilities for micro-robotics and reconfigurable systems

On the Properties of Self-Thermophoretic Janus Particles: From Hot Brownian Motion to Motility Landscapes

This thesis investigates several phenomena that are associated with (self-)thermophoretic Janus particles with hemispheres made from different materials serving as a paradigm for active propul- sion on the microscale. (i) The dynamics of a single Janus sphere in the external temperature field created by an immobilized heat source is studied. I show that the particle’s angular velocity is solely determined by the temperature profile on the equator between the Janus particle’s hemispheres and their phoretic mobility contrast. (ii) The distinct polarization-density patterns observed for active-particle suspensions in activity landscapes are addressed. The results of my approximate theoretical model agree well with exact numerical and measurement data for a thermophoretic microswimmer, and can serve as a template for more complex applications. The essential physics behind the formal results is robustly captured and elucidated by a schematic two-species “run- and-tumble” model. (iii) I investigate coarse-grained models of suspended self-thermo- phoretic microswimmers. Starting from atomistic molecular dynamics simulations, the coarse-grained de- scription of the fluid in terms of a local molecular temperature field is verified, and effective nonequilibrium temperatures characterizing the particle’s so called hot Brownian motion are mea- sured from simulations. They are theoretically shown to remain relevant for any further spatial coarse-graining towards a hydrodynamic description of the entire suspension as a homogeneous complex fluid.In dieser Arbeit untersuche ich mehrere Phänomene, die im Zusammenhang mit (selbst-)thermo- phoretischen Janusteilchen auftreten. Diese Teilchen bestehen aus zwei Halbkugeln mit unter- schiedlichen Materialeigenschaften und dienen in dieser Arbeit als Musterbeispiel für aktive Fort- bewegung auf der Mikroskala. (i) Die Dynamik eines einzelnen Janusteilchens im externen Temper- aturfeld einer ortsfesten Heizquelle wird untersucht. Es wird gezeigt, dass die Winkelgeschwindigkeit des Teilchens ausschließlich durch das Temperaturprofil am Äquator zwischen den Hemisphären des Janusteilchens und dem Unterschied ihrer phoretischen Mobilitäten bestimmt wird. (ii) Ich befasse mich mit den charakteristischen Polarisations- und Dichteprofilen, die für aktive Teilchen in Aktivitätslandschaften beobachtet werden. Die Ergebnisse meines approximativen theoretis- chen Modells stimmen gut mit exakten numerischen Lösungen und Messdaten für einen ther- mophoretischen Mikroschwimmer überein und können als Vorlage für komplexere Anwendungen dienen. Die wesentliche Physik hinter den formalen Ergebnissen wird durch ein schematisches Zwei-Spezies-“Run-and-Tumble”-Modell erfasst und erklärt. (iii) Ich untersuche Coarse-Graining- Modelle von suspendierten selbst-thermophoretischen Mikroschwimmern. Ausgehend von atom- istischen molekulardynamischen Simulationen wird die grobkörnige (coarse-grained) Beschreibung des Fluids in Form eines lokalen molekularen Temperaturfeldes verifiziert. Anschließend berechne ich effektive Nichtgleichgewichtstemperaturen, die die sogenannte heiße Brownsche Bewegung der Teilchen charakterisieren, und vergleiche diese mit Simulationsdaten. Es wird gezeigt, dass diese effektiven Temperaturen für jede weitere räumliche Vergröberung hin zu einer hydrodynamischen Beschreibung der gesamten Suspension als homogenes komplexes Fluid relevant bleiben

Characterization of Flagellar Propulsion of Soft Microrobotic Sperm in a Viscous Heterogeneous Medium

Several microorganisms swim by a beating flagellum more rapidly in solutions with gel-like structure than they do in low-viscosity mediums. In this work, we aim to model and investigate this behavior in low Reynolds numbers viscous heterogeneous medium using soft microrobotic sperm samples. The microrobots are actuated using external magnetic fields and the influence of immersed obstacles on the flagellar propulsion is investigated. We use the resistive-force theory to predict the deformation of the beating flagellum, and the method of regularized Stokeslets for computing Stokes flows around the microrobot and the immersed obstacles. Our analysis and experiments show that obstacles in the medium improves the propulsion even when the Sperm number is not optimal (S-p not equal 2.1). Experimental results also show propulsion enhancement for concentration range of 0 - 5 % at relatively low actuation frequencies owing to the pressure gradient created by obstacles in close proximity to the beating flagellum. At relatively high actuation frequency, speed reduction is observed with the concentration of the obstacles

Synthesis of new pyrazolium based tunable aryl alkyl ionic liquids and their use in removal of methylene blue from aqueous solution

In this study, two new pyrazolium based tunable aryl alkyl ionic liquids, 2-ethyl-1-(4-methylphenyl)-3,5- dimethylpyrazolium tetrafluoroborate (3a) and 1-(4-methylphenyl)-2-pentyl-3,5-dimethylpyrazolium tetrafluoroborate (3b), were synthesized via three-step reaction and characterized. The removal of methylene blue (MB) from aqueous solution has been investigated using the synthesized salts as an extractant and methylene chloride as a solvent. The obtained results show that MB was extracted from aqueous solution with high extraction efficiency up to 87 % at room temperature at the natural pH of MB solution. The influence of the alkyl chain length on the properties of the salts and their extraction efficiency of MB was investigated