Locomotion of bovine spermatozoa during the transition from individual cells to bundles.

Various locomotion strategies employed by microorganisms are observed in complex biological environments. Spermatozoa assemble into bundles to improve their swimming efficiency compared to individual cells. However, the dynamic mechanisms for the formation of sperm bundles have not been fully characterized. In this study, we numerically and experimentally investigate the locomotion of spermatozoa during the transition from individual cells to bundles of two cells. Three consecutive dynamic behaviors are found across the course of the transition: hydrodynamic attraction/repulsion, alignment, and synchronization. The hydrodynamic attraction/repulsion depends on the relative orientation and distance between spermatozoa as well as their flagellar wave patterns and phase shift. Once the heads are attached, we find a stable equilibrium of the rotational hydrodynamics resulting in the alignment of the heads. The synchronization results from the combined influence of hydrodynamic and mechanical cell-to-cell interactions. Additionally, we find that the flagellar beat is regulated by the interactions during the bundle formation, whereby spermatozoa can synchronize their beats to enhance their swimming velocity.

CeFlowBot: A Biomimetic Flow-Driven Microrobot that Navigates under Magneto-Acoustic Fields.

Aquatic organisms within the Cephalopoda family (e.g., octopuses, squids, cuttlefish) exist that draw the surrounding fluid inside their bodies and expel it in a single jet thrust to swim forward. Like cephalopods, several acoustically powered microsystems share a similar process of fluid expulsion which makes them useful as microfluidic pumps in lab-on-a-chip devices. Herein, an array of acoustically resonant bubbles are employed to mimic this pumping phenomenon inside an untethered microrobot called CeFlowBot. CeFlowBot contains an array of vibrating bubbles that pump fluid through its inner body thereby boosting its propulsion. CeFlowBots are later functionalized with magnetic layers and steered under combined influence of magnetic and acoustic fields. Moreover, acoustic power modulation of CeFlowBots is used to grasp nearby objects and release it in the surrounding workspace. The ability of CeFlowBots to navigate remote environments under magneto-acoustic fields and perform targeted manipulation makes such microrobots useful for clinical applications such as targeted drug delivery. Lastly, an ultrasound imaging system is employed to visualize the motion of CeFlowBots which provides means to deploy such microrobots in hard-to-reach environments inaccessible to optical cameras.

Real-Time Multi-Modal Sensing and Feedback for Catheterization in Porcine Tissue.

OBJECTIVE: In this study, we introduce a multi-modal sensing and feedback framework aimed at assisting clinicians during endovascular surgeries and catheterization procedures. This framework utilizes state-of-the-art imaging and sensing sub-systems to produce a 3D visualization of an endovascular catheter and surrounding vasculature without the need for intra-operative X-rays. METHODS: The catheterization experiments within this study are conducted inside a porcine limb undergoing motions. A hybrid position-force controller of a robotically-actuated ultrasound (US) transducer for uneven porcine tissue surfaces is introduced. The tissue, vasculature, and catheter are visualized by integrated real-time US images, 3D surface imaging, and Fiber Bragg Grating (FBG) sensors. RESULTS: During externally-induced limb motions, the vasculature and catheter can be reliably reconstructed at mean accuracies of 1.9±0.3 mm and 0.82±0.21 mm, respectively. CONCLUSIONS: The conventional use of intra-operative X-ray imaging to visualize instruments and vasculature in the human body can be reduced by employing improved diagnostic technologies that do not operate via ionizing radiation or nephrotoxic contrast agents. SIGNIFICANCE: The presented multi-modal framework enables the radiation-free and accurate reconstruction of significant tissues and instruments involved in catheterization procedures.

A GPU-Accelerated Model-Based Tracker for Untethered Submillimeter Grippers.

Miniaturized grippers that possess an untethered structure are suitable for a wide range of tasks, ranging from micromanipulation and microassembly to minimally invasive surgical interventions. In order to robustly perform such tasks, it is critical to properly estimate their overall configuration. Previous studies on tracking and control of miniaturized agents estimated mainly their 2D pixel position, mostly using cameras and optical images as a feedback modality. This paper presents a novel solution to the problem of estimating and tracking the 3D position, orientation and configuration of the tips of submillimeter grippers from marker-less visual observations. We consider this as an optimization problem, which is solved using a variant of the Particle Swarm Optimization algorithm. The proposed approach has been implemented in a Graphics Processing Unit (GPU) which allows a user to track the submillimeter agents online. The proposed approach has been evaluated on several image sequences obtained from a camera and on B-mode ultrasound images obtained from an ultrasound probe. The sequences show the grippers moving, rotating, opening/closing and grasping biological material. Qualitative results obtained using both hydrogel (soft) and metallic (hard) grippers with different shapes and sizes ranging from 750 microns to 4 mm (tip to tip), demonstrate the capability of the proposed method to track the agent in all the video sequences. Quantitative results obtained by processing synthetic data reveal a tracking position error of 25 ± 7 µm and orientation error of 1.7 ± 1.3 degrees. We believe that the proposed technique can be applied to different stimuli responsive miniaturized agents, allowing the user to estimate the full configuration of complex agents from visual marker-less observations.

Model predictive control of a robotically actuated delivery sheath for beating heart compensation.

Minimally invasive surgery (MIS) during cardiovascular interventions reduces trauma and enables the treatment of high-risk patients who were initially denied surgery. However, restricted access, reduced visibility and control of the instrument at the treatment locations limits the performance and capabilities of such interventions during MIS. Therefore, the demand for technology such as steerable sheaths or catheters that assist the clinician during the procedure is increasing. In this study, we present and evaluate a robotically actuated delivery sheath (RADS) capable of autonomously and accurately compensating for beating heart motions by using a model-predictive control (MPC) strategy. We develop kinematic models and present online ultrasound segmentation of the RADS that are integrated with the MPC strategy. As a case study, we use pre-operative ultrasound images from a patient to extract motion profiles of the aortic heart valve (AHV). This allows the MPC strategy to anticipate for AHV motions. Further, mechanical hysteresis in the steering mechanism is compensated for in order to improve tip positioning accuracy. The novel integrated system is capable of controlling the articulating tip of the RADS to assist the clinician during cardiovascular surgery. Experiments demonstrate that the RADS follows the AHV motion with a mean positioning error of 1.68 mm. The presented modelling, imaging and control framework could be adapted and applied to a range of continuum-style robots and catheters for various cardiovascular interventions.

Needle path planning and steering in a three-dimensional non-static environment using two-dimensional ultrasound images.

Needle insertion is commonly performed in minimally invasive medical procedures such as biopsy and radiation cancer treatment. During such procedures, accurate needle tip placement is critical for correct diagnosis or successful treatment. Accurate placement of the needle tip inside tissue is challenging, especially when the target moves and anatomical obstacles must be avoided. We develop a needle steering system capable of autonomously and accurately guiding a steerable needle using two-dimensional (2D) ultrasound images. The needle is steered to a moving target while avoiding moving obstacles in a three-dimensional (3D) non-static environment. Using a 2D ultrasound imaging device, our system accurately tracks the needle tip motion in 3D space in order to estimate the tip pose. The needle tip pose is used by a rapidly exploring random tree-based motion planner to compute a feasible needle path to the target. The motion planner is sufficiently fast such that replanning can be performed repeatedly in a closed-loop manner. This enables the system to correct for perturbations in needle motion, and movement in obstacle and target locations. Our needle steering experiments in a soft-tissue phantom achieves maximum targeting errors of 0.86 ± 0.35 mm (without obstacles) and 2.16 ± 0.88 mm (with a moving obstacle).

Untethered soft magnetic pump for microfluidics-based Marangoni surfer.

Microfluidics has enabled the miniaturization of fluidic systems for various biomedical and industrial applications, including small-scale robotic propulsion. One mechanism for generating propulsive force through microfluidics is by exploiting the solutal Marangoni effect via releasing surfactant on the air-water interface. Surfactants locally reduce the surface tension, which leads to a surface stress that can propel the floating robot, called Marangoni surfer. However, so far the release of the surfactant is not controllable. In this study, we combine microfluidics-based Marangoni propulsion with a novel untethered magnetic pumping mechanism to enhance its controllability. The proposed magnetic micropump capitalizes on the interaction force between two soft magnets, which can generate a pumping force of 4.64 mN to actuate a membrane, and achieve a deformation of 450 µm. Net flow is achieved using a nozzle/diffuser flow rectifier whose efficacy as a function of the channel geometry is numerically studied. We investigate the flow rate of the pump with regard to the actuation frequency. Finally, we demonstrate its ability to control the motion of the Marangoni surfer.

Minimally designed thermo-magnetic dual responsive soft robots for complex applications.

The fabrication of thermo-magnetic dual-responsive soft robots often requires intricate designs to implement complex locomotion patterns and utilize the implemented responsive behaviors. This work demonstrates a minimally designed soft robot based on poly-N-isopropylacrylamide (pNIPAM) and ferromagnetic particles, showcasing excellent control over both thermo- and magnetic responses. Free radical polymerization enables the magnetic particles to be entrapped homogeneously within the polymeric network. The integration of magnetic shape programming and temperature response allows the robot to perform various tasks including shaping, locomotion, pick-and-place, and release maneuvers of objects using independent triggers. The robot can be immobilized in a gripping state through magnetic actuation, and a subsequent increase in temperature transitions the robot from a swollen to a collapsed state. The temperature switch enables the robot to maintain a secured configuration while executing other movements via magnetic actuation. This approach offers a straightforward yet effective solution for achieving full control over both stimuli in dual-responsive soft robotics.

Magnetic Soft Helical Manipulators with Local Dipole Interactions for Flexibility and Forces.

Magnetic continuum manipulators (MCMs) are a class of continuum robots that can be actuated without direct contact by an external magnetic field. MCMs operating in confined workspaces, such as those targeting medical applications, require flexible magnetic structures that contain combinations of magnetic components and polymers to navigate long and tortuous paths. In cylindrical MCM designs, a significant trade-off exists between magnetic moment and bending flexibility as the ratio between length and diameter decreases. In this study, we propose a new MCM design framework that enables increasing diameter without compromising on flexibility and magnetic moment. Magnetic soft composite helices constitute bending regions of the MCM and are separated by permanent ring magnets. Local dipole interactions between the permanent magnets can reduce bending stiffness, depending on their size and spacing. For the particular segment geometry presented herein, the local dipole interactions result in a 31% increase in angular deflection of composite helices inside an external magnetic field, compared to helices without local interactions. In addition, we demonstrate fabrication, maneuverability, and example applications of a multisegment MCM in a phantom of the abdominal aorta, such as passing contrast dye and guidewires.

Flagellar Propulsion of Sperm Cells Against a Time-Periodic Interaction Force.

Sperm cells undergo complex interactions with external environments, such as a solid-boundary, fluid flow, as well as other cells before arriving at the fertilization site. The interaction with the oviductal epithelium, as a site of sperm storage, is one type of cell-to-cell interaction that serves as a selection mechanism. Abnormal sperm cells with poor swimming performance, the major cause of male infertility, are filtered out by this selection mechanism. In this study, collinear bundles, consisting of two sperm cells, generate propulsive thrusts along opposite directions and allow to observe the influence of cell-to-cell interaction on flagellar wave-patterns. The developed elasto-hydrodynamic model demonstrates that steric and adhesive forces lead to highly symmetrical wave-pattern and reduce the bending amplitude of the propagating wave. It is measured that the free cells exhibit a mean flagellar curvature of 6.4 ± 3.5 rad mm-1 and a bending amplitude of 13.8 ± 2.8 rad mm-1 . After forming the collinear bundle, the mean flagellar curvature and bending amplitude are decreased to 1.8 ± 1.1 and 9.6 ± 1.4 rad mm-1 , respectively. This study presents consistent theoretical and experimental results important for understanding the adaptive behavior of sperm cells to the external time-periodic force encountered during sperm-egg interaction.

A Magnetic Bio-Inspired Soft Carrier as a Temperature-Controlled Gastrointestinal Drug Delivery System.

Currently, gastrointestinal bleeding in the colon wall and the small bowel is diagnosed and treated with endoscopes. However, the locations of this condition are often problematic to treat using traditional flexible and tethered tools. New studies commonly consider untethered devices for solving this problem. However, there still exists a gap in the extant literature, and more research is needed to diagnose and deliver drugs in the lower gastrointestinal tract using soft robotic carriers. This paper discusses the development of an untethered, magnetically-responsive bio-inspired soft carrier. A molding process is utilized to produce prototypes from Diisopropylidene-1,6-diphenyl-1,6-hexanediol-based Polymer with Ethylene Glycol Dimethacrylate (DiAPLEX) MP-3510 - a shape memory polymer with a low transition temperature to enable the fabrication of these carriers. The soft carrier design is validated through simulation results of deformation caused by magnetic elements embedded in the carrier in response to an external field. The thermal responsiveness of the fabricated prototype carriers is assessed ex vivo and in a phantom. The results indicate a feasible design capable of administering drugs to a target inside a phantom of a large intestine. The soft carrier introduces a method for the controlled release of drugs by utilizing the rubbery modulus of the polymer and increasing the recovery force through magnetic actuation.

Locally Addressable Energy Efficient Actuation of Magnetic Soft Actuator Array Systems.

Advances in magnetoresponsive composites and (electro-)magnetic actuators have led to development of magnetic soft machines (MSMs) as building blocks for small-scale robotic devices. Near-field MSMs offer energy efficiency and compactness by bringing the field source and effectors in close proximity. Current challenges of near-field MSM are limited programmability of effector motion, dimensionality, ability to perform collaborative tasks, and structural flexibility. Herein, a new class of near-field MSMs is demonstrated that combines microscale thickness flexible planar coils with magnetoresponsive polymer effectors. Ultrathin manufacturing and magnetic programming of effectors is used to tailor their response to the nonhomogeneous near-field distribution on the coil surface. The MSMs are demonstrated to lift, tilt, pull, or grasp in close proximity to each other. These ultrathin (80 µm) and lightweight (100 gm-2 ) MSMs can operate at high frequency (25 Hz) and low energy consumption (0.5 W), required for the use of MSMs in portable electronics.

Two-photon microscopy for microrobotics: Visualization of micro-agents below fixed tissue.

Optical microscopy is frequently used to visualize microrobotic agents (i.e., micro-agents) and physical surroundings with a relatively high spatio-temporal resolution. However, the limited penetration depth of optical microscopy techniques used in microrobotics (in the order of 100 µm) reduces the capability of visualizing micro-agents below biological tissue. Two-photon microscopy is a technique that exploits the principle of two-photon absorption, permitting live tissue imaging with sub-micron resolution and optical penetration depths (over 500 µm). The two-photon absorption principle has been widely applied to fabricate sub-millimeter scale components via direct laser writing (DLW). Yet, its use as an imaging tool for microrobotics remains unexplored in the state-of-the-art. This study introduces and reports on two-photon microscopy as an alternative technique for visualizing micro-agents below biological tissue. In order to validate two-photon image acquisition for microrobotics, two-type micro-agents are fabricated and employed: (1) electrospun fibers stained with an exogenous fluorophore and (2) bio-inspired structure printed with autofluorescent resin via DLW. The experiments are devised and conducted to obtain three-dimensional reconstructions of both micro-agents, perform a qualitative study of laser-tissue interaction, and visualize micro-agents along with tissue using second-harmonic generation. We experimentally demonstrate two-photon microscopy of micro-agents below formalin-fixed tissue with a maximum penetration depth of 800 µm and continuous imaging of magnetic electrospun fibers with one frame per second acquisition rate (in a field of view of 135 × 135 µm2). Our results show that two-photon microscopy can be an alternative imaging technique for microrobotics by enabling visualization of micro-agents under in vitro and ex ovo conditions. Furthermore, bridging the gap between two-photon microscopy and the microrobotics field has the potential to facilitate in vivo visualization of micro-agents.

Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies.

OBJECTIVES: To evaluate the accuracy and speed of a novel robotic technique as an aid to perform magnetic resonance image (MRI)-guided prostate biopsies on patients with cancer suspicious regions. METHODS: A pneumatic controlled MR-compatible manipulator with 5 degrees of freedom was developed in-house to guide biopsies under real-time imaging. From 13 consecutive biopsy procedures, the targeting error, biopsy error and target displacement were calculated to evaluate the accuracy. The time was recorded to evaluate manipulation and procedure time. RESULTS: The robotic and manual techniques demonstrated comparable results regarding mean targeting error (5.7 vs 5.8 mm, respectively) and mean target displacement (6.6 vs 6.0 mm, respectively). The mean biopsy error was larger (6.5 vs 4.4 mm) when using the robotic technique, although not significant. Mean procedure and manipulation time were 76 min and 6 min, respectively using the robotic technique and 61 and 8 min with the manual technique. CONCLUSIONS: Although comparable results regarding accuracy and speed were found, the extended technical effort of the robotic technique make the manual technique - currently - more suitable to perform MRI-guided biopsies. Furthermore, this study provided a better insight in displacement of the target during in vivo biopsy procedures.

Macroscopic and microscopic observations of needle insertion into gels.

Needle insertion into soft tissue is one of the most common medical interventions. This study provides macroscopic and microscopic observations of needle-gel interactions. A gelatin mixture is used as a soft-tissue simulant. For the macroscopic studies, system parameters, such as insertion velocity, needle diameter, gel elasticity, needle tip shape (including bevel angle) and insertion motion profile, are varied, while the maximum insertion force and maximum needle deflection are recorded. The needle tip and gel interactions are observed using confocal microscopic images. Observations indicate that increasing the insertion velocity and needle diameter results in larger insertion forces and smaller needle deflections. Varying the needle bevel angle from 8 degrees to 82 degrees results in the insertion force increasing monotonically, while the needle deflection does not. These variations are due to the coupling between gel rupture and tip compression interactions, which are observed during microscopic studies. Increasing the gel elasticity results in larger insertion forces and needle deflections. Varying the tip shapes demonstrates that bevel-tipped needles produce the largest deflection, but insertion force does not vary among the tested tip shapes. Insertion with different motion profiles are performed. Results show that adding I Hz rotational motion during linear insertion decreases the needle deflection. Increasing the rotational motion from I Hz to 5 Hz decreases the insertion force, while the needle deflection remains the same. A high-velocity (250 mm/s and 300 mm/s) tapping during insertion yields no significant decrease in needle deflection and a slight increase in insertion force.

Intravascular Tracking of Micro-Agents Using Medical Ultrasound: Towards Clinical Applications.

OBJECTIVE: This study demonstrates intravascular micro-agent visualization by utilizing robotic ultrasound-based tracking and visual servoing in clinically-relevant scenarios. METHODS: Visual servoing path is planned intraoperatively using a body surface point cloud acquired with a 3D camera and the vessel reconstructed from ultrasound (US) images, where both the camera and the US probe are attached to the robot end-effector. Developed machine vision algorithms are used for detection of micro-agents from minimal size of 250 µm inside the vessel contour and tracking with error recovery. Finally, real-time positions of the micro-agents are used for servoing of the robot with the attached US probe. Constant contact between the US probe and the surface of the body is accomplished by means of impedance control. RESULTS: Breathing motion is compensated to keep constant contact between the US probe and the body surface, with minimal measured force of 2.02 N. Anthropomorphic phantom vessels are segmented with an Intersection-Over-Union (IOU) score of 0.93 ± 0.05, while micro-agent tracking is performed with up to 99.8% success rate at 28-36 frames per second. Path planning, tracking and visual servoing are realized over 80 mm and 120 mm long surface paths. CONCLUSION: Experiments performed using anthropomorphic surfaces, biological tissue, simulation of physiological movement and simulation of fluid flow through the vessels indicate that robust visualization and tracking of micro-agents involving human patients is an achievable goal.

Visualization of micro-agents and surroundings by real-time multicolor fluorescence microscopy.

Optical microscopy techniques are a popular choice for visualizing micro-agents. They generate images with relatively high spatiotemporal resolution but do not reveal encoded information for distinguishing micro-agents and surroundings. This study presents multicolor fluorescence microscopy for rendering color-coded identification of mobile micro-agents and dynamic surroundings by spectral unmixing. We report multicolor microscopy performance by visualizing the attachment of single and cluster micro-agents to cancer spheroids formed with HeLa cells as a proof-of-concept for targeted drug delivery demonstration. A microfluidic chip is developed to immobilize a single spheroid for the attachment, provide a stable environment for multicolor microscopy, and create a 3D tumor model. In order to confirm that multicolor microscopy is able to visualize micro-agents in vascularized environments, in vitro vasculature network formed with endothelial cells and ex ovo chicken chorioallantoic membrane are employed as experimental models. Full visualization of our models is achieved by sequential excitation of the fluorophores in a round-robin manner and synchronous individual image acquisition from three-different spectrum bands. We experimentally demonstrate that multicolor microscopy spectrally decomposes micro-agents, organic bodies (cancer spheroids and vasculatures), and surrounding media utilizing fluorophores with well-separated spectrum characteristics and allows image acquisition with 1280 [Formula: see text] 1024 pixels up to 15 frames per second. Our results display that real-time multicolor microscopy provides increased understanding by color-coded visualization regarding the tracking of micro-agents, morphology of organic bodies, and clear distinction of surrounding media.

SonoTweezer: An Acoustically Powered End-Effector for Underwater Micromanipulation.

Recent advances in contactless micromanipulation strategies have revolutionized prospects of robotic manipulators as next-generation tools for minimally invasive surgeries. In particular, acoustically powered phased arrays offer dexterous means of manipulation both in air and water. Inspired by these phased arrays, we present SonoTweezer: a compact, low-power, and lightweight array of immersible ultrasonic transducers capable of trapping and manipulation of sub-mm sized agents underwater. Based on a parametric investigation with numerical pressure field simulations, we design and create a six-transducer configuration, which is small compared to other reported multi-transducer arrays (16-256 elements). Despite the small size of array, SonoTweezer can reach pressure magnitudes of 300 kPa at a low supply voltage of 25 V to the transducers, which is in the same order of absolute pressure as multi-transducer arrays. Subsequently, we exploit the compactness of our array as an end-effector tool for a robotic manipulator to demonstrate long-range actuation of sub-millimeter agents over a hundred times the agent's body length. Furthermore, a phase-modulation over its individual transducers allows our array to locally maneuver its target agents at sub-mm steps. The ability to manipulate agents underwater makes SonoTweezer suitable for clinical applications considering water's similarity to biological media, e.g., vitreous humor and blood plasma. Finally, we show trapping and manipulation of micro-agents under medical ultrasound (US) imaging modality. This application of our actuation strategy combines the usage of US waves for both imaging and micromanipulation.