Advances in millimeter-scale fabrication processes have enabled rapid progress towards the development of flapping wing micro air vehicles with wing spans of several centimeters and a system mass on the order of 100mg. Concerning flight stability and control mechanisms for these mass and power limited devices, this dissertation explores the use of underactuated “mechanically intelligent” systems to passively regulate forces and torques encountered during flight. Several experiments demonstrate passive torque regulation in physical flapping wing systems. Finally, this dissertation concludes with a detailed description of the Printed Circuit MEMS manufacturing process, developed to address the practical problem of building complex insect-scale machines. / Engineering and Applied Sciences

In recent years, research efforts in the development of Micro Electro Mechanical Systems, (MEMS) including microactuators and micromanipulators, have attracted a great deal of attention. The development of microfabrication techniques has resulted in substantial progress in the miniaturization of devices such as electronic circuits. However, the research in MEMS still lags behind in terms of the development of reliable tools for post-fabrication processes and the precise and dexterous manipulation of individual micro size objects. Current micromanipulation mechanisms are prone to high costs, a large footprint, and poor dexterity and are labour intensive. To overcome such, the research in this thesis is focused on the utilization of microactuators in micromanipulation. Microactuators are compliant structures. They undergo substantial deflection during micromanipulation due to the considerable surface micro forces. Their dominance in governing micromanipulation is so compelling that their effects should be considered in designing microactuators and microsensors. In this thesis, the characterization of the surface micro forces and automated micromanipulation are investigated. An inexpensive experimental setup is proposed as a platform to replace Atomic Force Microscopy (AFM) for analyzing the force characterization of micro scale components. The relationship between the magnitudes of the surface micro forces and the parameters such as the velocity of the pushing process, relative humidity, temperature, hydrophilicity of the substrate, and surface area are empirically examined. In addition, a precision automated micromanipulation system is realized. A class of artificial neural networks (NN) is devised to estimate the unmodelled micro forces during the controlled pushing of micro size object along a desired path. Then, a nonlinear controller is developed for the controlled pushing of the micro objects to guarantee the stability of the closed loop system in the Lyapunov sense. To validate the performance of the proposed controller, an experimental setup is designed. The application of the proposed controller is extended to precisely push several micro objects, each with different characteristics in terms of the surface micro forces governing the manipulation process. The proposed adaptive controller is capable of learning to adjust its weights effectively when the surface micro forces change under varying conditions. By using the controller, a fully automated sequential positioning of three micro objects on a flat substrate is performed. The results are compared with those of the identical sequential pushing by using a conventional linear controller. The results suggest that artificial NNs are a promising tool for the design of adaptive controllers to accurately perform the automated manipulation of multiple objects in the microscopic scale for microassembly.

In recent years, research efforts in the development of Micro Electro Mechanical Systems, (MEMS) including microactuators and micromanipulators, have attracted a great deal of attention. The development of microfabrication techniques has resulted in substantial progress in the miniaturization of devices such as electronic circuits. However, the research in MEMS still lags behind in terms of the development of reliable tools for post-fabrication processes and the precise and dexterous manipulation of individual micro size objects. Current micromanipulation mechanisms are prone to high costs, a large footprint, and poor dexterity and are labour intensive. To overcome such, the research in this thesis is focused on the utilization of microactuators in micromanipulation. Microactuators are compliant structures. They undergo substantial deflection during micromanipulation due to the considerable surface micro forces. Their dominance in governing micromanipulation is so compelling that their effects should be considered in designing microactuators and microsensors. In this thesis, the characterization of the surface micro forces and automated micromanipulation are investigated. An inexpensive experimental setup is proposed as a platform to replace Atomic Force Microscopy (AFM) for analyzing the force characterization of micro scale components. The relationship between the magnitudes of the surface micro forces and the parameters such as the velocity of the pushing process, relative humidity, temperature, hydrophilicity of the substrate, and surface area are empirically examined. In addition, a precision automated micromanipulation system is realized. A class of artificial neural networks (NN) is devised to estimate the unmodelled micro forces during the controlled pushing of micro size object along a desired path. Then, a nonlinear controller is developed for the controlled pushing of the micro objects to guarantee the stability of the closed loop system in the Lyapunov sense. To validate the performance of the proposed controller, an experimental setup is designed. The application of the proposed controller is extended to precisely push several micro objects, each with different characteristics in terms of the surface micro forces governing the manipulation process. The proposed adaptive controller is capable of learning to adjust its weights effectively when the surface micro forces change under varying conditions. By using the controller, a fully automated sequential positioning of three micro objects on a flat substrate is performed. The results are compared with those of the identical sequential pushing by using a conventional linear controller. The results suggest that artificial NNs are a promising tool for the design of adaptive controllers to accurately perform the automated manipulation of multiple objects in the microscopic scale for microassembly.

Ionic electroactive polymer (IEAP) actuators are a class of electroactive polymer devices that exhibit electromechanical coupling through ion transport in the device. They consist of an ionomeric membrane coated with conductive network composites (CNCs) and conductive electrodes on both sides. A series of experiments on IEAP actuators with various types of CNCs has demonstrated the existence of a direct correlation between the performance of actuators and physical and structural properties of the CNCs. Nanostructure of CNC is especially important in hosting electrolyte and boosting ion mobility. This dissertation presents a series of systematic experiments and studies on IEAP actuators with two primary focuses: 1) CNC nanostructure, and 2) ionic interactions. A novel approach for fabrication of CNC thin-films enabled us to control physical and structural properties of the CNC thin-films. We, for the first time, facilitated use of layer-by-layer ionic self-assembly technique in fabrication of porous and conductive CNCs based on polymer and metal nanoparticles. Results were porous-conductive CNCs. We have studied the performance dependence of IEAP actuators on nano-composition and structure of CNCs by systematically varying the thickness, nanoparticle size and nanoparticle concentration of CNCs. We have also studied influence of the waveform frequency, free-ions and counterions of the ionomeric membrane on the performance and behavior of IEAP actuators. Using the LbL technique, we systematically changed the thickness of CNC layers consisting of gold nanoparticles (AuNPs) and poly(allylamine hydrochloride). It was observed that actuators consisting of thicker CNCs exhibit larger actuation curvature, which is evidently due to uptake of larger volume of electrolyte. Actuation response-time exhibited a direct correlation to the sheet-resistance of CNC, which was controlled by varying the AuNP concentration. It was observed that size and type of free-ions and counterion of ionomeric membrane are also influential on the actuation behavior or IEAP actuators and that the counterion of ionomeric membrane participates in the actuation process. / Ph. D.

The lack of efficacy of existing chemotherapeutic treatments of solid tumors is partially attributed to the limited diffusion distance of therapeutics and the low selectivity of anti-cancer drugs with respect to cancerous tissue, which also leads to high levels of systemic toxicity in patients. Thus, chemotherapy can be enhanced through improving anti-cancer drug carrier selectivity and transport properties. Several strains of gram positive (e.g. Clostridium and Bifidobacterium) and gram-negative (e.g. Salmonella Typhimurium and Escherichia coli) bacteria have been shown to possess the innate ability to preferentially colonize tumor tissues. The overall goal of this dissertation is to characterize the transport and sensing of Bacteria-Enabled Drug Delivery Systems (BEADS) in select relevant environments and to investigate the associated underlying principles. BEADS consist of an engineered abiotic load (i.e. drug-laden micro or nano-particles) and a living component (i.e. bacteria) for sensing and actuation purposes. Findings of this dissertation work are culminated in experimental demonstration of deeper penetration of the NanoBEADS within tumor tissue when compared to passively diffusing chemotherapeutic nanoparticles. Lastly, the transport mechanisms that Salmonella Typhimurium VNP20009 utilize to preferentially colonize solid tumors are also examined with the ultimate goal of engineering intelligent and more efficacious drug delivery vehicles for cancer therapy. / Ph. D.

Systemic chemotherapy is a major therapeutic approach for nearly all types and stages of cancer. Success of this treatment depends not only on the efficacy of the therapeutics but also on the transport of the drug to all tumor cells in sufficient concentrations. Intratumoral drug transport is limited by characteristics of the tumor microenvironment such as elevated interstitial pressure and sparse, irregular vascularization. Moreover, poor tumor selectivity, leads to systemic toxicity. Bacteria possess a host of characteristics that address the aforementioned challenges in conventional drug delivery approaches including tumor selectivity, preferential tumor colonization, effective tumor penetration, which can be augmented via genetic engineering. However, in clinical trials conducted to date, bacteria have rarely been able to inhibit tumor growth solely by their presence in the tumor. The overall goal of this doctoral dissertation is to develop a novel tumor treatment system based on Salmonella Typhimurium VNP20009 (genetically modified for preferential tumor colonization and attenuation) coupled with biodegradable copolymer, poly(lactic-co-glycolic acid) nanoparticles, hereafter referred to as NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery System). To this end, a NanoBEADS fabrication procedure that is robust and repeatable was established and a microfluidic chemotaxis-based sorting platform for the separation NanoBEADS from unattached nanoparticles was developed. The transport efficacy of NanoBEADS compared to the commonly used passively-diffusing nanoparticle was investigated in vitro and in vivo and the intratumoral penetration of the therapeutic vectors was quantified using a custom image processing algorithm. The mechanism of intratumoral penetration was elucidated through 2D and 3D invasion assays. Lastly, we developed a biophysical model of intratumoral transport of NanoBEADS based on the intratumoral penetration experimental results towards the theoretical evaluation of the drug transport profile following the administration of NanoBEADS. / PHD / Currently, the transport of chemotherapeutic drugs into tumors is limited by numerous characteristics of the tumor microenvironment. This problem is exacerbated by poor tumor selectivity, leading to severe side effects to patients. Bacteria possess a host of characteristics that address the aforementioned shortcomings in conventional drug delivery approaches including preferential tumor colonization and anti-tumor effects, which may be mediated naturally or enhanced via genetic engineering. The overall goal of this doctoral dissertation is to develop a novel tumor treatment system based on genetically modified bacteria for safety and efficiency, Salmonella Typhimurium VNP20009 coupled with a polymeric nanoparticles, hereafter referred to as NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery Systems). To this end, a NanoBEADS fabrication procedure that is robust and repeatable was established and a microfluidic chemotaxis-based sorting platform for the separation NanoBEADS from unattached nanoparticles was developed. The transport efficiency of NanoBEADS compared to the commonly used nanoparticle was investigated in vitro and in vivo and the intratumoral penetration of the therapeutic vectors was quantified using a custom image processing algorithm. The mechanism of intratumoral penetration was elucidated through 2D and 3D invasion assays. Lastly, we developed a biophysical model of intratumoral transport of NanoBEADS based on the intratumoral penetration experimental results towards the theoretical evaluation of the drug transport profile following the administration of NanoBEADS.

Precise manipulation of micro objects became great interest in engineering and science with the advancements in microengineering and microfabrication. In this thesis, a magnetically levitated microgripper is presented for microhandling tasks. The use of magnetic levitation for positioning reveals the problems associated with modeling of complex surface forces and the use of jointed parts or wires. The power required for the levitation of the microgripper is generated by an external drive unit that makes further minimization of the gripper possible. The gripper is made of a biocompatible material and can be activated remotely. These key features make the microgripper a great candidate for manipulation of micro components and biomanipulation. In order to achieve magnetic levitation of microrobots, the magnetic field generated by the magnetic levitation setup is simulated. The magnetic flux density in the air gap region is improved by the integration of permanent magnets and an additional electromagnet to the magnetic loop assembly. The levitation performance is evaluated with millimeter size permanent magnets. An eddy current damping method is implemented and the levitation accuracy is doubled by reducing the positioning error to 20.3 µm. For a MEMS-compatible microrobot design, the electrodeposition of Co-Ni-Mn-P magnetic thin films is demonstrated. Magnetic films are deposited on silicon substrate to form the magnetic portion of the microrobot. The electrodeposited films are extensively characterized. The relationship between the deposition parameters and structural properties is discussed leading to an understanding of the effect of deposition parameters on the magnetic properties. It is shown that both in-plane and out-of-plane magnetized films can be obtained using electrodeposition with slightly differentiated deposition parameters. The levitation of the electrodeposited magnetic samples shows a great promise toward the fabrication of levitating MEMS devices. The end-effector tool of the levitating microrobot is selected as a microgripper that can achieve various manipulation operations such as pulling, pushing, tapping, grasping and repositioning. The microgripper is designed based on a bent-beam actuation technique. The motion of the gripper fingers is achieved by thermal expansion through laser heat absorption. This technique provided non-contact actuation for the levitating microgripper. The analytical model of the displacement of the bent-beam actuator is developed. Different designs of microgripper are fabricated and thoroughly characterized experimentally and numerically. The two microgripper designs that lead to the maximum gripper deflection are adapted for the levitating microrobot. The experimental results show that the levitating microrobot can be positioned in a volume of 3 x 3 x 2 cm^3. The positioning error is measured as 34.3 µm and 13.2 µm when electrodeposited magnets and commercial permanent magnets are used, respectively. The gripper fingers are successfully operated on-the-fly by aligning a visible wavelength laser beam on the gripper. Micromanipulation of 100 µm diameter electrical wire, 125 µm diameter optical fiber and 1 mm diameter cable strip is demonstrated. The microgripper is also positioned in a closed chamber without sacrificing the positioning accuracy.

Precise manipulation of micro objects became great interest in engineering and science with the advancements in microengineering and microfabrication. In this thesis, a magnetically levitated microgripper is presented for microhandling tasks. The use of magnetic levitation for positioning reveals the problems associated with modeling of complex surface forces and the use of jointed parts or wires. The power required for the levitation of the microgripper is generated by an external drive unit that makes further minimization of the gripper possible. The gripper is made of a biocompatible material and can be activated remotely. These key features make the microgripper a great candidate for manipulation of micro components and biomanipulation. In order to achieve magnetic levitation of microrobots, the magnetic field generated by the magnetic levitation setup is simulated. The magnetic flux density in the air gap region is improved by the integration of permanent magnets and an additional electromagnet to the magnetic loop assembly. The levitation performance is evaluated with millimeter size permanent magnets. An eddy current damping method is implemented and the levitation accuracy is doubled by reducing the positioning error to 20.3 µm. For a MEMS-compatible microrobot design, the electrodeposition of Co-Ni-Mn-P magnetic thin films is demonstrated. Magnetic films are deposited on silicon substrate to form the magnetic portion of the microrobot. The electrodeposited films are extensively characterized. The relationship between the deposition parameters and structural properties is discussed leading to an understanding of the effect of deposition parameters on the magnetic properties. It is shown that both in-plane and out-of-plane magnetized films can be obtained using electrodeposition with slightly differentiated deposition parameters. The levitation of the electrodeposited magnetic samples shows a great promise toward the fabrication of levitating MEMS devices. The end-effector tool of the levitating microrobot is selected as a microgripper that can achieve various manipulation operations such as pulling, pushing, tapping, grasping and repositioning. The microgripper is designed based on a bent-beam actuation technique. The motion of the gripper fingers is achieved by thermal expansion through laser heat absorption. This technique provided non-contact actuation for the levitating microgripper. The analytical model of the displacement of the bent-beam actuator is developed. Different designs of microgripper are fabricated and thoroughly characterized experimentally and numerically. The two microgripper designs that lead to the maximum gripper deflection are adapted for the levitating microrobot. The experimental results show that the levitating microrobot can be positioned in a volume of 3 x 3 x 2 cm^3. The positioning error is measured as 34.3 µm and 13.2 µm when electrodeposited magnets and commercial permanent magnets are used, respectively. The gripper fingers are successfully operated on-the-fly by aligning a visible wavelength laser beam on the gripper. Micromanipulation of 100 µm diameter electrical wire, 125 µm diameter optical fiber and 1 mm diameter cable strip is demonstrated. The microgripper is also positioned in a closed chamber without sacrificing the positioning accuracy.

The non-contact nature of magnetic actuation makes it useful in a variety of microscale applications, from microfluidics and lab-on-a-chip devices to classical MEMS or even microrobotics. Ferromagnetic materials like nickel are particularly attractive, because they can be easily deposited and patterned using traditional lithography-based microscale fabrication methods. However, the response of ferromagnetic materials in a magnetic field can be difficult to predict. When placed in a magnetic field, high magnetization is induced in these ferromagnetic materials, which in turn generates force and/or torque on the ferromagnetic bodies. The magnitude and direction of these forces are highly dependent on the type of material used, the volume and aspect ratio of the ferromagnetic material, as well as the spatial distribution and magnitude of the magnetic field. It is important to understand these complex interactions in order to optimize force and torque generated, particularly given common limitations found in microfabrication, where it is often challenging to deposit large volumes of ferromagnetic material using conventional microdeposition methods, and power availability is also often limited, which in turn limits the ability to generate strong electromagnetic fields for actuation. This work represents a theoretical analysis and experimental validation in macro scale to determine best practices when designing ferromagnetic actuators for microscale applications. Specifically, the use of nickel thin film prisms actuated in spatially uniform electromagnetic fields. These constraints were chosen because uniform magnetic fields can be readily generated with a simple and inexpensive Helmholtz coil design, and the uniformity makes actuation force independent of location, minimizing the need for spatial precision in devices. Nickel can also be easily deposited using evaporation or sputtering, generally in forms of thin-films.

<p>Over the years, research and development of micro-force sensing techniques has gained a lot of traction, especially for microrobotic applications, such as micromanipulation and biomedical material characterization studies. Moreover, in recent years, new microfabrication techniques have been developed, such as two-photon polymerization (TPP), which enables fast prototyping, high resolution features, and the utilization of a wide range of materials. In general, the main goals of this work are to improve the resolution and range of novel vision-based force sensors, create microrobotic and micromanipulation systems capable of tackling a multitude of applications, and ensuring these systems are flexible and provide a sold foundation to the advancement of the field as a whole.</p> <p><br></p> <p>The current work can be divided into three main parts: (i) a wireless magnetic microrobot with 2D vision-based force sensing, (ii) a 3D vision-based force sensing probe for tethered micromanipulators, and (iii) a micromanipulation system capable of accurately controlling and performing advanced tasks. The vision-based force sensors developed here have resolutions ranging from the mN range to even sub-$\mu$N range, depending on the material used, geometry, and overall footprint. </p> <p><br></p> <p>In part (i), the microrobot has been developed mainly for biomedical applications \textit{in vitro}, with the ability to perform mechanical characterization and microassembly tasks of different rigid and biomedical materials. In part (ii), a similar sensor mechanic is used, but now adapted to a micromanipulation probe, which is able to detect forces in three dimensions and work in dry environments. In conjunction with the micromanipulation system described in part (iii), the system is capable of performing advanced assembly applications, including accurate assembly and 3D mounting of microparts. </p> <p><br></p> <p>With the introduction of TPP technologies to these works, the next generation of adaptable microrobotics and micromanipulation systems for advanced biomedical applications is starting to take shape, ever more versatile, smaller, more accurate, and with more advanced capabilities. This work shows the progression of these overall systems and gives a glimpse of what is possible with TPP and the technologies to come.</p>