Autonomous planning and control of soft untethered grippers in unstructured environments

The use of small, maneuverable, untethered and reconfigurable robots could provide numerous advantages in various micromanipulation tasks. Examples include microassembly, pick-and-place of fragile microobjects for lab-on-a-chip applications, assisted hatching for in-vitro fertilization and minimally invasive surgery. This study assesses the potential of soft untethered magnetic grippers as alternatives or complements to conventional tethered or rigid micromanipulators. We demonstrate closed-loop control of untethered grippers and automated pick-and-place of biological material on porcine tissue in an unstructured environment. We also demonstrate the ability of the soft grippers to recognize and sort non-biological micro-scale objects. The fully autonomous nature of the experiments is made possible by the integration of planning and decision-making algorithms, as well as by closed-loop temperature and electromagnetic motion control. The grippers are capable of completing pick-and-place tasks of biological material at an average velocity of 1.8±0.71 mm/s and a drop-off error of 0.62±0.22 mm. Color-sensitive sorting of three micro-scale objects is completed at a velocity of 1.21±0.68 mm/s and a drop-off error of 0.85±0.41 mm. Our findings suggest that improved autonomous un-tethered grippers could augment the capabilities of current soft-robotic instruments especially in advanced tasks involving manipulation

A Robust controller for micro-sized agents: The prescribed performance approach

Applications such as micromanipulation and minimally invasive surgery can be performed using micro-sized agents. For instance, drug-loaded magnetic micro-/nano- particles can enable targeted drug delivery. Their precise manipulation can be assured using a robust motion controller. In this paper, we design a closed-loop controller-observer pair for regulating the position of microagents. The prescribed performance technique is applied to control the microagents to follow desired motion trajectories. The position of the microagents are obtained using microscopic images and image processing. The velocities of the microagents are obtained using an iterative learning observer. The algorithm is tested experimentally on spherical magnetic microparticles that have an average diameter of 100 m. The steady-state errors obtained by the algorithm are 20 m. The errors converge to the steady-state in approximately 8 second

Magnetic motion control and planning of untethered soft grippers using ultrasound image feedback

Soft miniaturized untethered grippers can be used to manipulate and transport biological material in unstructured and tortuous environments. Previous studies on control of soft miniaturized grippers employed cameras and optical images as a feedback modality. However, the use of cameras might be unsuitable for localizing miniaturized agents that navigate within the human body. In this paper, we demonstrate the wireless magnetic motion control and planning of soft untethered grippers using feedback extracted from B-mode ultrasound images. Results show that our system employing ultrasound images can be used to control the miniaturized grippers with an average tracking error of 0.4±0.13 mm without payload and 0.36±0.05 mm when the agent performs a transportation task with a payload. The proposed ultrasound feedback magnetic control system demonstrates the ability to control miniaturized grippers in situations where visual feedback cannot be provided via cameras

Nanomaterial-decorated micromotors for enhanced photoacoustic imaging

Micro-and nanorobots have the potential to perform non-invasive drug delivery, sensing, and surgery in living organisms, with the aid of diverse medical imaging techniques. To perform such actions, microrobots require high spatiotemporal resolution tracking with real-time closed-loop feedback. To that end, photoacoustic imaging has appeared as a promising technique for imaging microrobots in deep tissue with higher molecular specificity and contrast. Here, we present different strategies to track magnetically-driven micromotors with improved contrast and specificity using dedicated contrast agents (Au nanorods and nanostars). Furthermore, we discuss the possibility of improving the light absorption properties of the employed nanomaterials considering possible light scattering and coupling to the underlying metal-oxide layers on the micromotor’s surface. For that, 2D COMSOL simulation and experimental results were correlated, confirming that an increased spacing between the Au-nanostructures and the increase of thickness of the underlying oxide layer lead to enhanced light absorption and preservation of the characteristic absorption peak. These characteristics are important when visualizing the micromotors in a complex in vivo environment, to distinguish them from the light absorption properties of the surrounding natural chromophores

Medical Imaging of Microrobots: Toward In Vivo Applications

Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications

An experimental comparison of path planning techniques applied to micro-sized magnetic agents

Micro-sized agents can be used in applications suchas microassembly, micromanipulation, and minimally invasive surgeries. Magnetic agents such as paramagnetic microparticles can be controlled to deliver pharmaceutical agents to difficult-toaccess regions within the human body. In order to autonomously move these microparticles toward a target/goal area, an obstaclefree path must be computed using path planning algorithms. Several path planning algorithms have been developed in the literature, however, to the best of our knowledge, only few have been employed in an experimental scenario. In this paper we perform an experimental comparison of six path planning algorithms when applied to the motion control of paramagnetic microparticles. Among the families of deterministic and probabilistic path planners we select the ones that we consider the most fundamental, such as: A* with quadtrees, A* with uniform grids, D* Lite, Artificial Potential Field, Probabilistic Roadmap and Rapidly-exploring Random Tree. We consider a 2D environment made by both dynamic and static obstacles. Four scenarios are evaluated. Three metrics such as computation time, length of the trajectory performed by the microparticle, and time to reach the goal are used to compare the planners. Experimental results reveal equivalence between almost all the considered planners in terms of trajectory length and completion time. Concerning the computation time, A* with quadtrees and Artificial Potential Field achieve the best performances

Wireless magnetic-based closed-loop control of self-propelled microjets

In this study, we demonstrate closed-loop motion control of self-propelled microjets under the influence of external magnetic fields. We control the orientation of the microjets using external magnetic torque, whereas the linear motion towards a reference position is accomplished by the thrust and pulling magnetic forces generated by the ejecting oxygen bubbles and field gradients, respectively. The magnetic dipole moment of the microjets is characterized using the U-turn technique, and its average is calculated to be 1.3x10-10 A.m2 at magnetic field and linear velocity of 2 mT and 100 μm/s, respectively. The characterized magnetic dipole moment is used in the realization of the magnetic force-current map of the microjets. This map in turn is used for the design of a closed-loop control system that does not depend on the exact dynamical model of the microjets and the accurate knowledge of the parameters of the magnetic system. The motion control characteristics in the transient- and steady-states depend on the concentration of the surrounding fluid (hydrogen peroxide solution) and the strength of the applied magnetic field. Our control system allows us to position microjets at an average velocity of 115 μm/s, and within an average region-of-convergence of 365 μm

Novel formulations for magnetic-resonance imaging guided theranostics

Recent advances in bioimaging, biochemistry and bioinformatics have facilitated the development of personalized and precision medicine. Theranostics, a combination of imaging modalities and therapeutic agents, have garnered increasing attention in this context, thanks to their potential to monitor and control treatment for individual patients. An attractive strategy to achieve this goal involves the development of therapy guided by magnetic resonance imaging (MRI). MRI, possessing a number of benefits including a high degree of soft tissue contrast, low invasiveness, high depth of penetration and good spatial resolution, could offer advanced imaging-guided therapy enabling precise and time-resolved assessment of disease conditions and therapeutic progression. The goal of this PhD thesis is to develop novel formulations based on polymeric, inorganic or hybrid materials using two pharmaceutical fabrication techniques (electrohydrodynamic atomisation or spray drying), and explore their potential in MRI-guided chemotherapy. Five different types of formulation carrying MRI contrast agents and chemotherapeutic agents were fabricated. Chapter 3 reports the fabrication of pH-responsive formulations via electrodynamic atomization, loaded with superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents and the model chemotherapeutic carmofur. These platforms are able to protect the cargo from release acidic conditions representative of the stomach, while at neutral pH the relaxivity is tightly correlated to the extent of drug release. Chapter 4 describes a series of dual responsive systems with distinct morphology, comprising of pH-responsive Eudragit shells with SPIONs, and thermo-responsive core loading carmofur. The fibres are found to have better thermo-responsive properties compared to microparticles, and the relaxivity display clear linear relationships with drug release data. Chapter 5 focuses on using spray drying to fabricate nano-in-micro particles based on a synthetic polymer with an upper capital solution temperature. The microparticles encapsulate drug-loaded layered double hydroxide nanosheets, have thermo-sensitive release and relaxivity profile, and in vitro cell studies reveal that the formulations permit synergistic hyperthermia-aided chemotherapy. Chapter 6 details the preparation and characterization of four gadolinium doped layered double hydroxides to develop theranostic platforms carrying chemotherapeutics with high T1-relaxivity. In Chapter 7, polydopamine-coated polycaprolactone/poly(lactic-co-glycolic) acid nanofibers are developed via co-axial electrospinning, which are loaded with dug-loaded LDH nanocomposites in the core. In vitro studies reflect sustained release of chemotherapeutics, and highly effective cytotoxic effects on tumour cells with the polydopamine coated formulations, which was further enhanced at higher levels of glutathione

Design and Implementation of Electromagnetic Actuation System to Actuate Micro/NanoRobots in Viscous Environment

The navigation of Micro/Nanorobots (MNRs) with the ability to track a selected trajectory accurately holds significant promise for different applications in biomedicine, providing methods for diagnoses and treatments inside the human body. The critical challenge is ensuring that the required power can be generated within the MNR. Furthermore, ensuring that it is feasible for the robot to travel inside the human body with the necessary power availability. Currently, MNRs are widely driven either by exogenous power sources (light energy, magnetic fields, electric fields, acoustics fields, etc.) or by endogenous energy sources, such as chemical interaction energy. Various driving techniques have been established, including piezoelectric as a driving source, thermal driving, electro-osmotic force driven by biological bacteria, and micro-motors powered by chemical fuel. These driving techniques have some restrictions, mainly when used in biomedicine. External magnetic fields are another potential power source of MNRs. Magnetic fields can permeate deep tissues and be safe for human organisms. As a result, magnetic fields’ magnetic forces and moments can be applied to MNRs without affecting biological fluids and tissues. Due to their features and characteristics of magnetic fields in generating high power, they are naturally suited to control the electromagnetically actuated MNRs in inaccessible locations due to their ability to go through tiny spaces. From the literature, it can be inferred from the available range of actuation technologies that magnetic actuation performs better than other technologies in terms of controllability, speed, flexibility of the working environment, and far less harm may cause to people. Also, electromagnetic actuation systems may come in various configurations that offer many degrees of freedom, different working mediums, and controllability schemes. Although this is a promising field of research, further simulation studies, and analysis, new smart materials, and the development and building of new real systems physically, and testing the concepts under development from different aspects and application requirements are required to determine whether these systems could be implemented in natural clinical settings on the human body. Also, to understand the latest development in MNRs and the actuation techniques with the associated technologies. Also, there is a need to conduct studies and comparisons to conclude the main research achievements in the field, highlight the critical challenges waiting for answers, and develop new research directions to solve and improve the performance. Therefore, this thesis aims to model and analyze, simulate, design, develop, and implement (with complete hardware and software integration) an electromagnetic actuation (EMA) system to actuate MNRs in the sixdimensional (6D) motion space inside a relatively large region of interest (ROI). The second stage is a simulation; simulation and finite element analysis were conducted. COMSOL multi-physics software is used to analyze the performance of different coils and coil pairs for Helmholtz and Maxwell coil configurations and electromagnetic actuation systems. This leads to the following.: • Finite element analysis (FEA) demonstrates that the Helmholtz coils generate a uniform and consistent magnetic field within a targeted ROI, and the Maxwell coils generate a uniform magnetic gradient. • The possibility to combine Helmholtz and Maxwell coils in different space dimensions. With the ability to actuate an MNR in a 6D space: 3D as a position and 3D as orientation. • Different electromagnetic system configurations are proposed, and their effectiveness in guiding an MNR inside a mimicked blood vessel environment was assessed. • Three pairs of Helmholtz coils and three pairs of coils of Maxwell coils are combined to actuate different size MNRs inside a mimicked blood vessel environment and in 6D. Based on the modeling results, a magnetic actuation system prototype that can control different sizes MNRs was conceived. A closed-loop control algorithm was proposed, and motion analysis of the MNR was conducted and discussed for both position and orientation. Improved EMA location tracking along a chosen trajectory was achieved using a PID-based closed-loop control approach with the best possible parameters. Through the model and analysis stage, the developed system was simulated and tested using open- and closed-loop circumstances. Finally, the closedloop controlled system was concluded and simulated to verify the ability of the proposed EMA to actuate an MN under different trajectory tracking examples with different dimensionality and for different sizes of MNRs. The last stage is developing the experimental setup by manufacturing the coils and their base in-house. Drivers and power supplies are selected according to the specifications that actuate the coils to generate the required magnetic field. Three digital microscopes were integrated with the electromagnetic actuation system to deliver visual feedback aiming to track in real-time the location of the MNR in the 6D high viscous fluidic environment, which leads to enabling closed-loop control. The closed-loop control algorithm is developed to facilitate MNR trajectory tracking and minimize the error accordingly. Accordingly, different tests were carried out to check the uniformity of the magnetic field generated from the coils. Also, a test was done for the digital microscope to check that it was calibrated and it works correctly. Experimental tests were conducted in 1D, 2D plane, and 3D trajectories with two different MNR sizes. The results show the ability of the proposed EMA system to actuate the two different sizes with a tracking error of 20-45 µm depending on the axis and the size of the MNR. The experiments show the ability of the developed EMA system to hold the MNR at any point within the 3D fluidic environment while overcoming the gravity effects. A comparison was made between the results achieved (in simulation and physical experiments) and the results deduced from the literature. The comparison shows that the thesis’s outcomes regarding the error and MNR size used are significant, with better performance relative to the MNR size and value of the error