Science Robotics, 3(17), Science Robotics, April 2018 (article)
Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine.
A reliable, real time multi-sensor fusion functionality is crucial for localization of actively controlled capsule endoscopy robots, which are an emerging, minimally invasive diagnostic and therapeutic technology for the gastrointestinal (GI) tract. In this study, we propose a novel multi-sensor fusion approach based on a particle filter that incorporates an online estimation of sensor reliability and a non-linear kinematic model learned by a recurrent neural network. Our method sequentially estimates the true robot pose from noisy pose observations delivered by multiple sensors. We experimentally test the method using 5 degree-of-freedom (5-DoF) absolute pose measurement by a magnetic localization system and a 6-DoF relative pose measurement by visual odometry. In addition, the proposed method is capable of detecting and handling sensor failures by ignoring corrupted data, providing the robustness expected of a medical device. Detailed analyses and evaluations are presented using ex-vivo experiments on a porcine stomach model prove that our system achieves high translational and rotational accuracies for different types of endoscopic capsule robot trajectories.
In Proceedings 2017 IEEE International Conference on Robotics and Automation (ICRA), pages: 3404-3410, IEEE, Piscataway, NJ, USA, IEEE International Conference on Robotics and Automation (ICRA), May 2017 (inproceedings)
Magnetic untethered millirobots, which are actuated and controlled by remote magnetic fields, have been proposed for medical applications due to their ability to safely pass through tissues at long ranges. For example, magnetic resonance imaging (MRI) systems with a 3-7 T constant unidirectional magnetic field and 3D gradient coils have been used to actuate magnetic robots. Such magnetically constrained systems place limits on the degrees of freedom that can be actuated for untethered devices. This paper presents a design and actuation methodology for a magnetic millirobot that exhibits both position and orientation control in 2D under a magnetic field, dominated by a constant unidirectional magnetic field as found in MRI systems. Placing a spherical permanent magnet, which is free to rotate inside the millirobot and located away from the center of mass, allows the generation of net forces and torques with applied 3D magnetic field gradients. We model this system in a 3D planar case and experimentally demonstrate open-loop control of both position and orientation by the applied 2D field gradients. The actuation performance is characterized across the most important design variables, and we experimentally demonstrate that the proposed approach is feasible.
Science Advances, 3(5):e1602522, American Association for the Advancement of Science, May 2017 (article)
Dynamic self-assembled material systems constantly consume energy to maintain their spatiotemporal structures and functions. Programmable self-assembly translates information from individual parts to the collective whole. Combining dynamic and programmable self-assembly in a single platform opens up the possibilities to investigate both types of self-assembly simultaneously and to explore their synergy. This task is challenging because of the difficulty in finding suitable interactions that are both dissipative and programmable. We present a dynamic and programmable self-assembling material system consisting of spinning at the air-water interface circular magnetic micro-rafts of radius 50 μm and with cosinusoidal edge-height profiles. The cosinusoidal edge-height profiles not only create a net dissipative capillary repulsion that is sustained by continuous torque input but also enable directional assembly of micro-rafts. We uncover the layered arrangement of micro-rafts in the patterns formed by dynamic self-assembly and offer mechanistic insights through a physical model and geometric analysis. Furthermore, we demonstrate programmable self-assembly and show that a 4-fold rotational symmetry encoded in individual micro-rafts translates into 90° bending angles and square-based tiling in the assembled structures of micro-rafts. We anticipate that our dynamic and programmable material system will serve as a model system for studying nonequilibrium dynamics and statistical mechanics in the future
Lab on a Chip, 17(10):1705-1724, Royal Society of Chemistry, 2017 (article)
Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments.
Lab on a Chip, 16(22):4445-4457, Royal Society of Chemistry, October 2016 (article)
At the sub-millimeter scale, capillary forces enable robust and reversible adhesion between biological organisms and varied substrates. Current human-engineered mobile untethered micromanipulation systems rely on forces which scale poorly or utilize gripper-part designs that promote manipulation. Capillary forces, alternatively, are dependent upon the surface chemistry (which is scale independent) and contact perimeter, which conforms to the part surface. We report a mobile capillary microgripper that is able to pick and place parts of various materials and geometries, and is thus ideal for microassembly tasks that cannot be accomplished by large tethered manipulators. We achieve the programmable assembly of sub-millimeter parts in an enclosed three-dimensional aqueous environment by creating a capillary bridge between the targeted part and a synthetic, untethered, mobile body. The parts include both hydrophilic and hydrophobic components: hydrogel, kapton, human hair, and biological tissue. The 200 μm untethered system can be controlled with five-degrees-of-freedom and advances progress towards autonomous desktop manufacturing for tissue engineering, complex micromachines, microfluidic devices, and meta-materials.
The International Journal of Robotics Research, 35(1-3):114-128, SAGE Publications Sage UK: London, England, June 2016 (article)
Existing remotely actuated magnetic microrobots exhibit a maximum of only five-degree-of-freedom (DOF) actuation, as creation of a driving torque about the microrobot magnetization axis is not achievable. This lack of full orientation control limits the effectiveness of existing microrobots for precision tasks of object manipulation and orientation for advanced medical, biological and micromanufacturing applications. This paper presents a magnetic actuation method that allows remotely powered microrobots to achieve full six-DOF actuation by considering the case of a non-uniform magnetization profile within the microrobot body. This non-uniform magnetization allows for additional rigid-body torques to be induced from magnetic forces via a moment arm. A general analytical model presents the working principle for continuous and discrete magnetization profiles, which is applied to permanent or non-permanent (soft) magnet bodies. Several discrete-magnetization designs are also presented which possess reduced coupling between magnetic forces and induced rigid-body torques. Design guidelines are introduced which can be followed to ensure that a magnetic microrobot design is capable of six-DOF actuation. A simple permanent-magnet prototype is fabricated and used to quantitatively demonstrate the accuracy of the analytical model in a constrained-DOF environment and qualitatively for free motion in a viscous liquid three-dimensional environment. Results show that desired forces and torques can be created with high precision and limited parasitic actuation, allowing for full six-DOF actuation using limited feedback control
Proceedings of the IEEE, 103(2):205-224, IEEE, March 2015 (article)
Untethered robots miniaturized to the length scale of millimeter and below attract growing attention for the prospect of transforming many aspects of health care and bioengineering. As the robot size goes down to the order of a single cell, previously inaccessible body sites would become available for high-resolution in situ and in vivo manipulations. This unprecedented direct access would enable an extensive range of minimally invasive medical operations. Here, we provide a comprehensive review of the current advances in biomedical untethered mobile milli/microrobots. We put a special emphasis on the potential impacts of biomedical microrobots in the near future. Finally, we discuss the existing challenges and emerging concepts associated with designing such a miniaturized robot for operation inside a biological environment for biomedical applications.
Our goal is to understand the principles of Perception, Action and Learning in autonomous systems that successfully interact with complex environments and to use this understanding to design future systems