Hybrid Hydrogel-Magnet Actuated Capsule for Automatic Gut Microbiome Sampling.

OBJECTIVE: Non-invasive, pill-sized capsules can provide intestinal fluid sampling to easily retrieve site-specific gut microbiome samples for studies in nutrition and chronic diseases. However, capsules with both automatic sampling and active locomotion are uncommon due to limited onboard space. This paper presents a novel hybrid hydrogel-magnet actuated capsule featuring: i) pH-responsive hydrogels that will automatically trigger fluid sampling at an environmental pH of > 6 and ii) active locomotion by an external rotating magnetic field. METHOD: Two capsule designs were fabricated (Design A: 31 µL sampling volume with dimensions 8 mm × 19 mm, Design B: 41 µL sampling volume with dimensions 8 mm × 21 mm). They were immersed in simulated gastric (pH = 1.2) and simulated intestinal fluid (pH = 6.8) to test for automatic intestinal fluid sampling. An external rotating magnetic field was applied to test for active locomotion. Finally, seal tests were performed to demonstrate sample contamination mitigation. RESULTS: Preliminary experiments showed that sampling occurred quickly and automatically in simulated intestinal fluid at 6 - 15 hours, active locomotion via rotation, rolling, and tumbling were possible at magnetic field magnitudes < 10 mT, oil piston seals were better at mitigating sample contamination than water piston seals, and minimum o-ring seal pressures limits of 1.95 and 1.69 kPa for Design A and B respectively were sufficient against intra-abdominal pressures. SIGNIFICANCE: This work presents the ability to impart capsule multi-functionality in a compact manner without onboard electronics or external triggering for sampling.

Medical Microrobots.

Scientists around the world have long aimed to produce miniature robots that can be controlled inside the human body to aid doctors in identifying and treating diseases. Such microrobots hold the potential to access hard-to-reach areas of the body through the natural lumina. Wireless access has the potential to overcome drawbacks of systemic therapy, as well as to enable completely new minimally invasive procedures. The aim of this review is fourfold: first, to provide a collection of valuable anatomical and physiological information on the target working environments together with engineering tools for the design of medical microrobots; second, to provide a comprehensive updated survey of the technological state of the art in relevant classes of medical microrobots; third, to analyze currently available tracking and closed-loop control strategies compatible with the in-body environment; and fourth, to explore the challenges still in place, to steer and inspire future research.

Screen-Printed Resistive Tactile Sensor for Monitoring Tissue Interaction Forces on a Surgical Magnetic Microgripper.

With the recent development of novel miniaturized magnetically controlled microgripper surgical tools (of diameter 4 mm) for robot-assisted minimally invasive endoscopic intraventricular surgery, the surgeon loses feedback from direct physical contact with the tissue. In this case, surgeons will have to rely on tactile haptic feedback technologies to retain their ability to limit tissue trauma and its associated complications during operations. Current tactile sensors for haptic feedback cannot be integrated to the novel tools primarily due to size limitations and low force range requirements of these highly dextrous surgical operations. This study introduces the design and fabrication of a novel 9 mm2, ultra-thin and flexible resistive tactile sensor whose operation is based on variation of resistivity due to changes in contact area and piezoresistive (PZT) effect of the sensor's materials and sub-components. Structural optimization was performed on the sub-components of the sensor design, including microstructures, interdigitated electrodes, and conductive materials in order to improve minimum detection force while maintaining low hysteresis and unwanted sensor actuation. To achieve a low-cost design suitable for disposable tools, multiple layers of the sensor sub-component were screen-printed to produce thin flexible films. Multi-walled carbon nanotubes and thermoplastic polyurethane composites were fabricated, optimized, and processed into suitable inks to produce conductive films to be assembled with printed interdigitated electrodes and microstructures. The assembled sensor's electromechanical performance indicated three distinct linear sensitivity modes within the sensing range of 0.04-1.3 N. Results also indicated repeatable and low-time responses while maintaining the flexibility and robustness of the overall sensor. This novel ultra-thin screen-printed tactile sensor of 110 µm thickness is comparable to more expensive tactile sensors in terms of performance and can be mounted onto the magnetically controlled micro-scale surgical tools to increase the safety and quality of endoscopic intraventricular surgeries.

Capsule robot pose and mechanism state detection in ultrasound using attention-based hierarchical deep learning.

Ingestible robotic capsules with locomotion capabilities and on-board sampling mechanism have great potential for non-invasive diagnostic and interventional use in the gastrointestinal tract. Real-time tracking of capsule location and operational state is necessary for clinical application, yet remains a significant challenge. To this end, we propose an approach that can simultaneously determine the mechanism state and in-plane 2D pose of millimeter capsule robots in an anatomically representative environment using ultrasound imaging. Our work proposes an attention-based hierarchical deep learning approach and adapts the success of transfer learning towards solving the multi-task tracking problem with limited dataset. To train the neural networks, we generate a representative dataset of a robotic capsule within ex-vivo porcine stomachs. Experimental results show that the accuracy of capsule state classification is 97%, and the mean estimation errors for orientation and centroid position are 2.0 degrees and 0.24 mm (1.7% of the capsule's body length) on the hold-out test set. Accurate detection of the capsule while manipulated by an external magnet in a porcine stomach and colon is also demonstrated. The results suggest our proposed method has the potential for advancing the wireless capsule-based technologies by providing accurate detection of capsule robots in clinical scenarios.

Design and Comparison of Magnetically-Actuated Dexterous Forceps Instruments for Neuroendoscopy.

Robot-assisted minimally invasive surgical (MIS) techniques offer improved instrument precision and dexterity, reduced patient trauma and risk, and promise to lessen the skill gap among surgeons. These approaches are common in general surgery, urology, and gynecology. However, MIS techniques remain largely absent for surgical applications within narrow, confined workspaces, such as neuroendoscopy. The limitation stems from a lack of small yet dexterous robotic tools. In this work, we present the first instance of a surgical robot with a direct magnetically-driven end effector capable of being deployed through a standard neuroendoscopic working channel (3.2 mm outer diameter) and operate at the neuroventricular scale. We propose a physical model for the gripping performance of three unique end-effector magnetization profiles and mechanical designs. Rates of blocking force per external magnetic flux density magnitude were 0.309 N/T, 0.880 N/T, and 0.351 N/T for the three designs which matched the physical model's prediction within 14.9% error. The rate of gripper closure per external magnetic flux density had a mean percent error of 11.2% compared to the model. The robot's performance was qualitatively evaluated during a pineal region tumor resection on a tumor analogue in a silicone brain phantom. These results suggest that wireless magnetic actuation may be feasible for dexterously manipulating tissue during minimally invasive neurosurgical procedures.

Local stimulation of osteocytes using a magnetically actuated oscillating beam.

Mechanical loading on bone tissue is an important physiological stimulus that plays a key role in bone growth, fracture repair, and treatment of bone diseases. Osteocytes (bone cells embedded in bone matrix) are well accepted as the sensor cells to mechanical loading and play a critical role in regulating the bone structure in response to mechanical loading. To understand the response of osteocytes to differential mechanical stimulation in physiologically relevant arrangements, there is a need for a platform which can locally stimulate bone cells with different levels of fluid shear stress. In this study, we developed a device aiming to achieve non-contact local mechanical stimulation of osteocytes with a magnetically actuated beam that generates the fluid shear stresses encountered in vivo. The stimulating beam was made from a composite of magnetic powder and polymer, where a magnetic field was used to precisely oscillate the beam in the horizontal plane. The beam is placed above a cell-seeded surface with an estimated gap height of 5 µm. Finite element simulations were performed to quantify the shear stress values and to generate a shear stress map in the region of interest. Osteocytes were seeded on the device and were stimulated while their intracellular calcium responses were quantified and correlated with their position and local shear stress value. We observed that cells closer to the oscillating beam respond earlier compared to cells further away from the local shear stress gradient generated by the oscillating beam. We have demonstrated the capability of our device to mimic the propagation of calcium signalling to osteocytes outside of the stimulatory region. This device will allow for future studies of osteocyte network signalling with a physiologically accurate localized shear stress gradient.

Millimeter-scale flexible robots with programmable three-dimensional magnetization and motions.

Flexible magnetic small-scale robots use patterned magnetization to achieve fast transformation into complex three-dimensional (3D) shapes and thereby achieve locomotion capabilities and functions. These capabilities address current challenges for microrobots in drug delivery, object manipulation, and minimally invasive procedures. However, possible microrobot designs are limited by the existing methods for patterning magnetic particles in flexible materials. Here, we report a method for patterning hard magnetic microparticles in an elastomer matrix. This method, based on ultraviolet (UV) lithography, uses controlled reorientation of magnetic particles and selective exposure to UV light to encode magnetic particles in planar materials with arbitrary 3D orientation with a geometrical feature size as small as 100 micrometers. Multiple planar microrobots with various sizes, different geometries, and arbitrary magnetization profiles can be fabricated from a single precursor in one process. Moreover, a 3D magnetization profile allows higher-order and multi-axis bending, large-angle bending, and combined bending and torsion in one sheet of polymer, creating previously unachievable shape changes and microrobotic locomotion mechanisms such as multi-arm power grasping and multi-legged paddle crawling. A physics-based model is also presented as a design tool to predict the shape changes under magnetic actuation.

Untethered Miniature Soft Robots: Modeling and Design of a Millimeter-Scale Swimming Magnetic Sheet.

The actuation and control of miniature soft robots are challenging problems due to their limited onboard space and flexible bodies. Smart magnetic materials are promising candidates to address these challenges since they can be powered and guided remotely by magnetic field for functionalities, such as swimming, grasping, and pumping. In this study, we program an undulatory swimming gait into a small rectangular sheet that is made of a flexible magnetic homogeneous composite. The sheet bears a sinusoidal magnetization profile throughout its body and deforms into undulatory shapes in a rotating uniform magnetic field that aligns with its length. The traveling wave-like deformation of the sheet interacts with the surrounding liquid and propels the sheet in a bidirectional nonholonomic swimming gait. Previous studies on this sheet were not able to model the deformation accurately or characterize the swimming systematically due to a lack of understanding of the underlying physical principles involved. For the first time, we develop a model from underlying physical principles to explain and predict the sheet deformation, which enables it to swim at air-water interfaces and generate propulsive forces under water with an additional stiff frame. The swimming capability and maneuverability of the millimeter-scale sheet are demonstrated in experiments, and its swimming performances in various scenarios are characterized quantitatively. The soft swimming sheet can potentially be used for microrobotic tasks, such as delivering cargo or transporting individual cells in poorly accessible workspaces.

3D shape evolution of microparticles and 3D enabled applications using non-uniform UV flow lithography (NUFL).

The generation of microparticles with non-spherical morphologies has generated extensive interest because of their enhanced physical properties that can increase their performance in a wide variety of clinical and industrial applications. A flow lithographic technique based on stop flow lithography (SFL) recently showed the ability to fabricate particles with 3D shapes via manipulation of the UV intensity profile in a simple 2D microfluidic channel. Here, we further explore this flow lithographic method, called non-uniform flow lithography (NUFL), to investigate the 3D-shape tuning ability for the generation of 3D magnetic microparticles and their potential applications. We characterize the morphological microparticle shape change through variation of polymerization objective, UV intensity, and solution opacity. We also couple the particles' intrinsic anisotropic magnetic properties with an external magnetic field to create chains of bullet- and bell-shaped particles and a valve-like micromachine. In addition, in contrast to other complex and multi-step methodologies, NUFL shows a simple route for the facile creation of 3D microstructure platforms such as microneedles with fully modifiable tip morphology. This method presents intriguing possibilities for growing research within 3D microstructure assembly, micromachine systems and minimally invasive medical interventions.

A generic label-free microfluidic microobject sorter using a magnetic elastic diverter.

Cell sorters play important roles in biological and medical applications, such as cellular behavior study and disease diagnosis and therapy. This work presents a label-free microfluidic sorter that has a downstream-pointing magnetic elastic diverter. Different with most existing magnetic sorters, the proposed device does not require the target microobjects to be intrinsically magnetic or coated with magnetic particles, giving users more flexibility in sorting criteria. The diverter is wirelessly deformed by an applied magnetic field, and its deformation induces a fluid vortex that sorts incoming microobjects, e.g., cells, to the collection outlet. The diverter does not touch samples in this process, reducing the sample contamination and damage risks. This sorter uses a magnetic field generated by off-chip electromagnetic coils that are centimeters away from the device. With simple structure and no on-chip circuits or coils, this device can be integrated with other lab-on-a-chip instruments in a sealed chip, ameliorating the safety concerns in handling hazardous samples. The parallel and independent control of two such diverters on a single chip were demonstrated, showing the potential of doubling the overall throughput or forming a two-stage cascaded sorter. The sorter was modeled based on the Euler-Bernoulli beam theory and its reliability was demonstrated by achieving a raw success rate of 96.68% in sorting 1506 registered microbeads. With a simple structure, the sorter is easy and cheap to fabricate. The advantages of the proposed sorter make it a promising multi-purpose sorting tool in both academic and industrial applications.

Programmable assembly of heterogeneous microparts by an untethered mobile capillary microgripper.

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.

Biomedical Applications of Untethered Mobile Milli/Microrobots.

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 biome dical 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.

Chemotactic steering of bacteria propelled microbeads.

Flagellated bacteria have been embraced by the micro-robotics community as a highly efficient microscale actuation method, capable of converting chemical energy into mechanical actuation for microsystems that require a small payload and high rate of actuation. Along with being highly motile, Serratia marcescens (S. marcescens), our bacterium species of interest, is a highly agile biomotor capable of being steered via chemotaxis. In this paper, we attached S. marcescens bacteria to polystyrene microbeads towards creating biohybrid that can propel themselves towards an attractive chemical source. Using a three-channel microfluidic device, linear chemical gradients are generated to compare the behavior of bacteria-propelled beads in the presence and absence of a chemoattractant, L-aspartate. We tested and compared the behavior of three different bacteria-attached bead sizes (5, 10 and 20 µm diameter) using a visual particle-tracking algorithm, and noted their behavioral differences. The results indicate that in the presence of a chemoattractant, the S. marcescens-attached polystyrene beads exhibit a clear indication of directionality and steering control through the coordination of the bacteria present on each bead. This directionality is observed in all bead size cases, suggesting potential for targeted payload delivery using such a biohybrid micro-robotic approach.