The study employs dynamic mode decomposition (DMD) to elucidate the underlying mechanisms contributing to the enhanced motility observed in sperm bundles, primarily focusing on the role of flagellar synchronization. The decomposition reveals that synchronized flagellar movements might be a key factor enabling sperm cells to attain higher velocities when connected in bundles. Through DMD, periodical characteristics of individual periodical motion patterns, such as frequency, amplitude, and modal growth/decay rates (from DMD eigenvalues), are characterized, elucidating main parameters of the dynamic behavior of these biological systems, such as dominant frequencies of periodical motion, as well as amplitudes and velocities. The implications of this research extend beyond understanding sperm bundle dynamics, as the methodology is adaptable for identifying healthy sperm cells based on their motility patterns. Additionally, the approach holds potential for broader applications in studying other flagellar-driven microorganisms, providing a valuable tool for comparative analysis across various species.

Magnetic microrobots have the potential to revolutionize medicine by navigating pathways to deliver precision-targeted therapy. However, a significant challenge arises. There commonly is a trade-off between magnetic responsiveness, detectability using medical imaging systems and cytotoxicity from increased amounts of magnetic content. Addressing this, we study biohybrid microrobots comprising clusters of iron oxide nanoparticle-coated sperm cells. These sperm-templated microrobots offer benefits over microrobots driven by live sperm, such as longer shelf-life and operation time, full directional and speed control and easy fabrication. To demonstrate their potential for use in clinical settings, we developed an X-ray-guided robotic platform investigating the magnetic response and detectability of these biohybrid clusters across varying nanoparticle concentrations, notably demonstrating simultaneous actuation and localization of sperm for the first time. These improvements advance the research closer to unleashing the potential of biohybrid microrobots for medical applications within the reproductive tract.

Kidney stones are some of the most common urinary diseases, affecting 12% of the population. The high prevalence and recurrence of this disease urges the development of more targeted and effective treatment with lower side effects and less invasiveness avoiding recurrence and prolonged drug administration. Particularly for recurring stone formers, the current methods of persistent drug treatment and repetitive surgeries for stone removal are unsatisfying solutions that bring a huge burden to the patients and healthcare systems. For these reasons, a delivery strategy that provides drug administration at the disease site through active, wireless transport is urgently needed to improve urinary tract disease treatment. A wireless treatment of kidney stones is proposed with the help of flexible, magnetically steered, enzymatically active robots. These robots are designed to navigate in the urinary tract and locally dissolve the stones by action of embedded urease. The robots are made of millimeter-sized, gelatin-based polymer strips with embedded micromagnets and encapsulated urease which constantly converts urea to increase urinary pH. This study demonstrates enhanced stone dissolution and the robots' magnetic navigation through the different parts of a 3D printed human urinary tract model. A clinical ultrasound system allows real-time localization of the robots. This research proposes a less invasive and more targeted strategy for medical interventions in the urinary tract with potential to circumvent surgery in case of uric acid kidney stones, which is relevant especially in the light of high prevalence and recurrence of kidney stones.

Soft, magnetically actuated robots offer promising potential for medical applications due to their simple fabrication, controllability, cargo loading ability and flexibility. This research focuses on the design, modeling, and behavior of soft, millimeter-scale filamentous robots composed of Gelatin Methacrylate (GelMa) hydrogels and embedded with micromagnets for magnetic actuation. These robots are designed for navigation within the human urinary tract. The study investigates two distinct configurations: screw-like and fin-like robots, each responding differently to an external rotating magnetic field. The screw-like robots propel forward through synchronized helical motion, while the fin-like robots rely on interaction with surrounding surfaces for crawling motion. Experimental frequency response tests reveal that fin-like robots exhibit three times faster motion than screw-like robots in confined environments, reaching velocities of up to 18 mm/s. Additionally, the influence of micromagnet location inside the filaments on their propulsion dynamics is explored, highlighting the potential for optimized performance in medical applications requiring navigation through narrow channels, such as the ureter. Further optimization is proposed to enhance control and performance in more complex biological environments.

Microorganisms, such as spermatozoa, exhibit rich behaviours when in close proximity to each other. However, their locomotion is not fully understood when coupled mechanically and hydrodynamically. In this study, we develop hydrodynamic models to investigate the locomotion of paired spermatozoa, predicting the fine structure of their swimming. Experimentally, sperm pairs are observed to transition between different modes of flagellar synchronisation: in-phase, anti-phase and lagged synchronisation. Using our models, we assess their swimming performances in these synchronisation modes in terms of average swimming speed, average power consumption, and swimming efficiency. The swimming performances of paired spermatozoa are shown to depend on their flagellar phase lag, flagellar waveforms, and the mechanical coupling between their heads.

Effective inhibition of sperm motility using a spermicide can be a promising approach in developing non-invasive male contraceptive agents. Copper is known to have contraceptive properties and has been used clinically for decades as intrauterine contraceptive devices (IUDs) for contraception in females. Beyond that, the spermicidal use of copper has not been explored much further, even though its use could also subdue the harmful effects caused by the hormonal contraceptive agents on the environment. Herein, we study the size, concentration and time dependent in vitro inhibition of bovine spermatozoa by copper microparticles. The effectivity in inhibiting the sperm motility is correlated to the amount of Cu2+ ions released by the particles during incubation. The copper particles cause direct suppression of sperm cell motility upon incubation and thereby show potential as sperm inhibiting, hormone free candidate for male contraception beyond condoms.

3D printing has emerged as a transformative technology in several manufacturing processes, being of particular interest in biomedical research for allowing the creation of 3D structures that mimic native tissues. The process of tissue 3D printing entails the construction of functional, 3D tissue structures. In this article, the integration of ferrofluid consisting of iron oxide nanoparticles into muscle cell-laden bioink is presented to obtain a 3D printed magnetically responsive muscle tissue, i.e., the ferromuscle. Using extrusion-based methods, the seamless integration of biocompatible ferrofluids are achieved to cell-laden hydrogels. The resulting ferromuscle tissue exhibits improved tissue differentiation demonstrated by the increased force output upon electrical stimulation compared to muscle tissue prepared without ferrofluid. Moreover, the magnetic component originating from the iron oxide nanoparticles allows magnetic guidance, as well as good cytocompatibility and biodegradability in cell culture. These findings offer a new versatile fabrication approach to integrate magnetic components into living constructs, with potential applications as bioactuators and for future integration in smart, functional muscle implants.

AbstractConventional microscopy‐driven sperm health monitoring systems suffer from high infrastructural costs and complex protocols. Here, a simple, economical sperm motility assessment system is proposed. Based on a cantilever‐deflection‐based direct force measurement system capable of detecting wetting forces in the range of ≈µN, it is found that the adhesion of live and motile sperm cell‐laden droplets is dependent on sperm motility in the suspension. Further, it is observed that the sperm motility inside the droplet decreases with time, and the adhesion of the concerned droplet with a master substrate demonstrates an increasing trend. Contrary to an immotile cell, the motile sperm, due to its inherent nature of swimming parallel to the contact line, induces a lower restrictive force on the receding triple contact line of the droplet. The study establishes a potential avenue by which sperm cell motility can be predicted via measuring the adhesion of the sperm‐cell‐laden droplets with a standard surface using the simple and automatable cantilever‐deflection method. These findings can pave a pathway toward developing a user‐friendly, expertise‐independent diagnostic platform for in‐house sperm health monitoring.

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.

Inspired by Richard Feynman's 1959 lecture and the 1966 film Fantastic Voyage, the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to scaling up production, commercialization, and regulatory frameworks that are crucial for transitioning from research to practical applications. We also emphasize the need for interdisciplinary collaboration to address both technical and nontechnical challenges, such as sustainability, ethics, and business considerations. Finally, we propose a roadmap for future research to accelerate the development of micro/nanorobots, positioning them as essential tools for addressing grand challenges and enhancing the quality of life.

Choanoflagellates are the only non-animals to contain key homologs of voltage-gated channels required for generating spontaneous action potentials. Action potentials activate high voltage-gated CaV channels which mediate neurotransmitter secretion at presynaptic nerve terminals (CaV2.1, CaV2.2), neuro-endocrine cells (CaV2.3) or sensory ribbon synapses associated with hearing (CaV1.3) and vision (CaV1.4). Cav1 channels in T-tubules align with ryanodine receptors of opposing sarcoplasmic reticulum (SR) membranes to mediate skeletal (CaV1.1) and cardiac (CaV1.2) muscle contractions.

This study introduces a novel machine learning-based methodology for automated detection and tracking of sperm cells within microscopic video recordings, aiming to elucidate the dynamics and motion patterns of individual sperm cells as well as sperm cell bundles. At first, the method identifies sperm cells across successive frames within a video sequence, facilitating the reconstruction of each cell's trajectory over time. Subsequently, we introduce a classification algorithm that distinguishes between solitary sperm cells, clusters of adjacent cells, and cohesive sperm cell bundles, addressing a gap in existing methodologies. Finally, we employ three conventional metrics for velocity assessment: Straight Line Velocity (VSL) and Average Path Velocity (VAP) and Curvilinear velocity (VCL), to quantify the movement speed of both individual sperm cells and bundles. The approach represents a significant advancement in the automated analysis of sperm motility and aggregation phenomena, providing a robust tool for researchers to study sperm behavior with enhanced accuracy and efficiency. The integration of machine learning techniques in sperm cell detection and tracking offers promising insights into reproductive biology and fertility studies. https://gitlab.fit.cvut.cz/horenjak/sperm_cell_tracking_app https://apps.datalab.fit.cvut.cz/sperm_tracking/

Accurate analysis of sperm cell flagellar dynamics plays a crucial role in understanding sperm motility as flagella parameters determine cell behavior in the spatiotemporal domain. In this study, we introduce a novel approach by harnessing Genetic Algorithms (GA) to analyze sperm flagellar motion characteristics and compare the results with the traditional decomposition method based on Fourier analysis. Our analysis focuses on extracting key parameters of the equation approximating flagellar shape, including beating period time, bending amplitude, mean curvature, and wavelength. Additionally, we delve into the extraction of phase constants and initial swimming directions, vital for the comprehensive study of sperm cell pairs and bundling phenomena. One significant advantage of GA over Fourier analysis is its ability to integrate sperm cell motion data, enabling a more comprehensive analysis. In contrast, Fourier analysis neglects sperm cell motion by transitioning to a sperm-centered coordinate system (material system). In our comparative study, GA consistently outperform the Fourier analysis-based method, yielding a remarkable reduction in fitting error of up to 70% and on average by 45%. An in-depth exploration of the sperm cell motion becomes indispensable in a wide range of applications from complexities of reproductive biology and medicine, to developing soft flagellated microrobots.

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.

An elevated level of blood uric acid (UA) can cause the formation of kidney stones, gout, and other diseases. We recently isolated a few DNA aptamers that can selectively bind to UA. In this work, we investigated the adsorption of a UA aptamer and random sequence DNA onto sodium urate crystals. Both DNA strands adsorbed similarly to urate crystals. In addition, both the UA aptamer and random DNA can inhibit the growth of urate crystals, suggesting a nonspecific adsorption mechanism rather than specific aptamer binding. In the presence of 500 nM DNA, the growth of needle-like sodium urate crystals was inhibited, and the crystals appeared granular after 6 h. To understand the mechanism of DNA adsorption, a few chemicals were added to desorb DNA. DNA bases contributed more to the adsorption than the phosphate backbone. Surfactants induced significant DNA desorption. Finally, DNA could also be adsorbed onto real UA kidney stones. This study provides essential insights into the interactions between DNA oligonucleotides and urate crystals, including the inhibition of growth and interface effects of DNA on sodium urate crystals.

Soft miniaturized robots, characterized by their simple manufacturability and manipulation, offer advantages in controllability and potential for medical applications. In the context of untethered robotic systems, a notable method of actuation is the use of magnetic fields. This research concentrates on the comprehensive modeling and fabrication of soft millimeter scale filaments subjected to magnetic actuation, designed to be applied in the human urinary tract. The investigation seeks to clarify the response of magnetic soft filaments with two distinct magnetic configurations to a rotating magnetic field resulting in a fin-like and a screw-like motion. This study analyses the degree of bending and the resulting forward motion by frequency response experiments. The results show that fin-like configuration of the magnetic robot results in 3 times faster motion than the screw-like robots in tubular confinement.

This study focuses on controlling and navigating IRONSperm (i.e., nanoparticle-coated sperm cells) clusters, highlighting their exceptional three-dimensional control capabilities using X-ray-guided magnetic fields. Through thorough exploration of inclination angles within the horizontal plane and actuation distances utilizing a permanent magnet actuator, the study uncovers IRONSperm's resilience to slope angles and its nuanced relationship with actuation distances. A detailed comparison of side and ceiling rolling illustrates the superiority of ceiling rolling on upwardly inclined surfaces, while side rolling excels in maneuverability on descending or horizontal branches. Experimental validation in a trifurcation phantom confirms these findings, emphasizing superior locomotion speed with ceiling rolling. Furthermore, it underscores successful navigation control in different directions, showcasing the potential for open-loop control within enclosed lumens and cavities. Additionally, the study accentuates the groundbreaking ability to localize and control IRONSperm clusters using X-ray-guided magnetic fields, marking a pivotal advancement for microrobotics for biomedical applications.

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.

Cell membrane potential affects the electrostatic self-assembly of magnetizable nanoparticles around the flagellum of sperm cells, leading to the formation of biohybrid microrobots (i.e., IRONSperm) with various bending stiffness. Here we explain the influence of bull sperm cell membrane potential on the formation of two types of IRONSperm samples that are produced by electrostatic self-assembly. The first type is a proximal-coated soft body with nanoparticles concentrated on the head to maintain high flexibility of the flagellum and create a passively propagating transverse bending wave under the influence of an external rotating magnetic field. The second type is a rigid-body with nanoparticles approximately uniformly distributed along the length to provide arbitrary geometry that maintains a constant chiral shape and propel by rotation about its long axis. We present a magneto-elastohydrodynamic model to predict the swimming speed at low Reynolds number for rigid IRONSperm with arbitrary shapes, and show that decreasing the bending stiffness allows the model to capture the behavior of its soft counterpart. While the response of a rigid chiral IRONSperm is distinguished by a greater swimming speed with a smooth decay with frequency, the benefit of a soft flagellum in certain scenarios would present a much smaller range of frequencies for wireless actuation.