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Abstract Intravascular surgical instruments require precise navigation within narrow vessels, necessitating maximum flexibility, minimal diameter, and high degrees of freedom. Existing tools often lack control during insertion due to undesirable bending, limiting vessel accessibility and risking tissue damage. Next-generation instruments aim to develop hemocompatible untethered devices controlled by external magnetic forces. Achieving this goal remains complex due to testing and implementation challenges in clinical environments. Here we assess the operational effectiveness of hemocompatible untethered magnetic robots using an ex vivo porcine aorta model. The results demonstrate a linear decrease in the swimming speed of untethered magnetic robots as arterial blood flow increases, with the capability to navigate against a maximum arterial flow rate of 67 mL/min. The untethered magnetic robots effectively demonstrate locomotion in a difficult-to-access target site, navigating through the abdominal aorta and reaching the distal end of the renal artery.

Soft bio‐microrobots have the potential to execute complex tasks in unexpected and harsh environments of the human body due to their dexterity and flexibility. The architectural designs of soft bio‐microrobots either replicate the motion of natural creatures or capitalize on their motility. Based on this design principle, biologically inspired microrobots that imitate the movements and functions of biological systems, such as starfish, bacteria, and sperm cells, as well as biohybrid microrobots that combine motile micro‐organisms or cells with functional components have been developed. Herein, an overview of the design principles, energy sources, and biomedical applications of existing soft bio‐microrobots is presented. It is shown that the incorporation of externally responsive material enables biologically inspired microrobots to change their shapes and imitate the motion of living organisms under external stimuli, and it is interpreted how biohybrid microrobots are guided through the tactic behavior of microorganisms or cells. Finally, perspectives on key challenges that soft bio‐microrobots must overcome to achieve in vivo biomedical applications are given.

Abstract 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 $$\times$$ × 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.

Untethered small‐scale helical devices (USHDs) have the potential to navigate blood vessels and treat vascular occlusive diseases. However, there are still many challenges in translating this method into clinical practice, both in terms of localization and wireless motion control. Herein, closed‐loop control characterization of the USHD against and along physiological fluid inside a blood vessel phantom at different penetration depths is shown. First the dynamic flow and ultrasound images noise affecting the measurement are modeled, and control system of the USHD based on bifurcation analysis of a 1D hydrodynamic model is designed. Then a region of attraction of a USHD driven by a permanent magnet robotic (PMR) system inside a blood vessel phantom around an equilibrium point is constructed. Further, the point‐to‐point closed‐loop control strategy is implemented based on the magnetic point‐dipole approximation and kinematic control of the PMR system and ultrasound feedback inside physiological fluid, blood vessel, and soft tissue. The frequency response of the USHD is characterized against and along the flowing streams of fetal bovine serum within different flow rates in the 6–20 mm s−1 range. The experimental results demonstrate the ability to navigate the USHD inside blood vessel phantoms with maximum position error of 1.99 ± 0.55 mm.

Cooperative behaviour of sperm is one of the mechanisms that plays a role in sperm competition. It has been observed in several species that spermatozoa interact with each other to form agglomerates or bundles. In this study, we investigate the effect of physical and biochemical factors that will most likely promote bundle formation in bull sperm. These factors include fluid viscosity, swim-up process, post-thaw incubation time and media additives which promote capacitation. While viscosity does not seem to influence the degree of sperm bundling, swim-up, post-thaw migration time and suppressed capacitation increase the occurrence of sperm bundles. This leads to the conclusion that sperm bundling is a result of hydrodynamic and adhesive interactions between the cells which occurs frequently during prolonged incubation times.

Abstract Technical design features for improving the way a passive elastic filament produces propulsive thrust can be understood by analyzing the deformation of sperm‐templated microrobots with segmented magnetization. Magnetic nanoparticles are electrostatically self‐assembled on bovine sperm cells with nonuniform surface charge, producing different categories of sperm‐templated microrobots. Depending on the amount and location of the nanoparticles on each cellular segment, magnetoelastic and viscous forces determine the wave pattern of each category during flagellar motion. Passively propagating waves are induced along the length of these microrobots using external rotating magnetic fields and the resultant wave patterns are measured. The response of the microrobots to the external field reveals distinct flow fields, propulsive thrust, and frequency responses during flagellar propulsion. This work allows predictions for optimizing the design and propulsion of flexible magnetic microrobots with segmented magnetization.

The development of magnetically powered microswimmers that mimic the swimming mechanisms of microorganisms is important for lab‐on‐a‐chip devices, robotics, and next‐generation minimally invasive surgical interventions. Governed by their design, most previously described untethered swimmers can be maneuvered only by varying the direction of applied rotational magnetic fields. This constraint makes even state‐of‐the‐art swimmers incapable of reversing their direction of motion without a prior change in the direction of field rotation, which limits their autonomy and ability to adapt to their environments. Also, due to constant magnetization profiles, swarms of magnetic swimmers respond in the same manner, which limits multiagent control only to parallel formations. Herein, a new class of microswimmers are presented which are capable of reversing their direction of swimming without requiring a reversal in direction of field rotation. These swimmers exploit heterogeneity in their design and composition to exhibit reversible bidirectional motion determined by the field precession angle. Thus, the precession angle is used as an independent control input for bidirectional swimming. Design variability is explored in the systematic study of two swimmer designs with different constructions. Two different precession angles are observed for motion reversal, which is exploited to demonstrate independent control of the two swimmer designs.

Several microorganisms swim by a beating flagellum more rapidly in solutions with gel-like structure than they do in low-viscosity mediums. In this work, we aim to model and investigate this behavior in low Reynolds numbers viscous heterogeneous medium using soft microrobotic sperm samples. The microrobots are actuated using external magnetic fields and the influence of immersed obstacles on the flagellar propulsion is investigated. We use the resistive-force theory to predict the deformation of the beating flagellum, and the method of regularized Stokeslets for computing Stokes flows around the microrobot and the immersed obstacles. Our analysis and experiments show that obstacles in the medium improves the propulsion even when the Sperm number is not optimal (Sp ≠ 2.1). Experimental results also show propulsion enhancement for concentration range of 0−5% at relatively low actuation frequencies owing to the pressure gradient created by obstacles in close proximity to the beating flagellum. At relatively high actuation frequency, speed reduction is observed with the concentration of the obstacles.

This work presents an approach for the localization and control of helical robots during removal of superficial blood clots inside in vitro and ex vivo models. The position of the helical robot is estimated using an array of Hall-effect sensors and precalculated magnetic field map of two synchronized rotating dipole fields. The estimated position is used to implement closed-loop motion control of the helical robot using the rotating dipole fields. We validate the localization accuracy by visual feedback and feature tracking inside the in vitro model. The experimental results show that the magnetic localization of a helical robot with diameter of 1 mm can achieve a mean absolute position error of 2.35 ± 0.4 mm (n = 20). The simultaneous localization and motion control of the helical robot enables propulsion toward a blood clot and clearing at an average removal rate of 0.67 ± 0.47 mm3/min. This method is used to localize the helical robot inside a rabbit aorta (ex vivo model), and the localization accuracy is validated using ultrasound feedback with a mean absolute position error of 2.6 mm.

The present study describes the fabrication of molecularly imprinted (MI) magnetic beaded fibers using electrospinning. Rosmarinic acid was selected as exemplary yet relevant template during molecular imprinting. A “design of experiments” methodology was used for optimizing the electrospinning process. Four factors, i.e., the concentration of the biodegradable polymer (polycaprolactone), the applied voltage, the flow rate, and the collector distance were varied in a central composite design. The production process was then optimized according to the suitability of the beaded fibers during microrobot fabrication, actuation, and drug release. The optimum average fiber diameter of MI beaded fibers was determined at 857 ± 390 nm with an average number of beads at 0.011 ± 0.002 per µm2. In vitro release profiles of the optimized MI beaded fibers revealed a lower burst rate and a more sustained release when compared to control fibers. Magnetic control of the MI beaded fibers was successfully tested by following selected waypoints along a star-shaped predefined trajectory. This study innovatively combines molecular imprinting technology with magnetic microrobots enabling targeted drug delivery systems that offer precise motion control via the magnetic response of microrobots along with selective uptake of a drug into the microrobot using MI beaded fibers in future.

We experimentally demonstrate the precise localization of spherical Pt-Silica Janus micromotors (diameter 5 μm) under the influence of controlled magnetic fields. First, we control the motion of the Janus micromotors in two-dimensional (2D) space. The control system achieves precise localization within an average region-of-convergence of 7 μm. Second, we show that these micromotors provide sufficient propulsion force, allowing them to overcome drag and gravitational forces and move both downwards and upwards. This propulsion is studied by moving the micromotors in three-dimensional (3D) space. The micromotors move downwards and upwards at average speeds of 19.1 μm/s and 9.8 μm/s, respectively. Moreover, our closed-loop control system achieves localization in 3D space within an average region-of-convergence of 6.3 μm in diameter. The precise motion control and localization of the Janus micromotors in 2D and 3D spaces provides broad possibilities for nanotechnology applications.