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

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

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