Magnetotactic Sperm Cells for Assisted Reproduction.

Biohybrid micromotors are active microscopic agents consisting of biological and synthetic components that are being developed as novel tools for biomedical applications. By capturing motile sperm cells within engineered microstructures, they can be controlled remotely while being propelled forward by the flagellar beat. This makes them an interesting tool for reproductive medicine that can enable minimally invasive sperm cell delivery to the oocyte in vivo, as a treatment for infertility. The generation of sperm-based micromotors in sufficiently large numbers, as they are required in biomedical applications has been challenging, either due to the employed fabrication techniques or the stability of the microstructure-sperm coupling. Here, biohybrid micromotors, which can be assembled in a fast and simple process using magnetic microparticles, are presented. These magnetotactic sperm cells show a high motility and swimming speed and can be transferred between different environments without large detrimental effects on sperm motility and membrane integrity. Furthermore, clusters of micromotors are assembled magnetically and visualized using dual ultrasound (US)/photoacoustic (PA) imaging. Finally, a protocol for the scaled-up assembly of micromotors and their purification for use in in vitro fertilization (IVF) is presented, bringing them closer to their biomedical implementation.

Medical microrobots in reproductive medicine from the bench to the clinic.

Medical microrobotics is an emerging field that aims at non-invasive diagnosis and therapy inside the human body through miniaturized sensors and actuators. Such microrobots can be tethered (e.g., smart microcatheters, microendoscopes) or untethered (e.g., cell-based drug delivery systems). Active motion and multiple functionalities, distinguishing microrobots from mere passive carriers and conventional nanomedicines, can be achieved through external control with physical fields such as magnetism or ultrasound. Here we give an overview of the key challenges in the field of assisted reproduction and how these new technologies could, in the future, enable assisted fertilization in vivo and enhance embryo implantation. As a case study, we describe a potential intervention in the case of recurrent embryo implantation failure, which involves the non-invasive delivery of an early embryo back to the fertilization site using magnetically-controlled microrobots. As the embryo will be in contact with the secretory oviduct fluid, it can develop under natural conditions and in synchrony with the endometrium preparation. We discuss the potential microrobot designs, including a proper selection of materials and processes, envisioning their translation from bench to animal studies and human medicine. Finally, we highlight regulatory and ethical considerations for bringing this technology to the clinic.

Nanomaterial-decorated micromotors for enhanced photoacoustic imaging.

Micro-and nanorobots have the potential to perform non-invasive drug delivery, sensing, and surgery in living organisms, with the aid of diverse medical imaging techniques. To perform such actions, microrobots require high spatiotemporal resolution tracking with real-time closed-loop feedback. To that end,  photoacoustic imaging has appeared as a promising technique for imaging microrobots in deep tissue with higher molecular specificity and contrast. Here, we present different strategies to track magnetically-driven micromotors with improved contrast and specificity using dedicated contrast agents (Au nanorods and nanostars). Furthermore, we discuss the possibility of improving the light absorption properties of the employed nanomaterials considering possible light scattering and coupling to the underlying metal-oxide layers on the micromotor's surface. For that, 2D COMSOL simulation and experimental results were correlated, confirming that an increased spacing between the Au-nanostructures and the increase of thickness of the underlying oxide layer lead to enhanced light absorption and preservation of the characteristic absorption peak. These characteristics are important when visualizing the micromotors in a complex in vivo environment, to distinguish them from the light absorption properties of the surrounding natural chromophores. Supplementary Information: The online version contains supplementary material available at 10.1007/s12213-023-00156-7.

Ultrasound Super-Resolution Flow Measurement of Suspensions in Narrow Channels.

Zinc-air flow batteries provide a scalable and cost-efficient energy storage solution. However, the achieved power density depends on the local flow conditions of the zinc particle suspension in the electrochemical cell. Numerical modeling is challenging due to the complex multiphase fluid and the interaction of flow and electrochemistry. Hence, performing experiments is crucial to investigate the influence of the flow conditions on the electrical performance, which requires flow instrumentation for the opaque suspension. To resolve the flow field across the 2.6-mm-wide flow channel of the investigated zinc-air flow battery (ZAB), a spatial resolution below 100 [Formula: see text] has to be typically achieved. Using ultrasound techniques, the achieved spatial resolution is limited by the trade-off between ultrasound frequency and imaging depth. This trade-off is even more critical for suspensions due to the scattering of the ultrasound, which increases strongly with frequency. We propose super-resolution particle tracking velocimetry (SRPTV) to overcome this limitation by achieving the required spatial resolution at a low ultrasound frequency. SRPTV is based on the super-resolution technique ultrasound localization microscopy, which is adapted to strongly scattering suspensions by using a dual-frequency-phased array and applying a coherence weighting beamformer to suppress speckles, which result from the scattering at the zinc particles of the suspension. The spatial resolution and the velocity uncertainty are characterized through calibration measurement and numerical simulation. A spatial resolution of 66 [Formula: see text] at an excitation wavelength of 330 [Formula: see text] was achieved, which is sufficient for performing flow investigation in an operational ZAB. The measured flow profile reveals shear-thinning properties and wall slip and therefore differs significantly from a parabolic flow profile of a Newtonian fluid. The presented technique offers potential for performing flow investigations of suspensions in small geometries with a spatial resolution beyond the diffraction limit.

Vector Flow Imaging of a Highly Laden Suspension in a Zinc-Air Flow Battery Model.

Flow batteries using suspension electrodes, e.g., zinc-air flow batteries (ZABs), have recently gained renewed interest as potential candidates for grid energy storage or mobile applications. The performance of ZABs depends on the local flow conditions of the suspension in the electrochemical cell, which acts as an electrode. Hence, it is crucial to measure and understand the complex flow characteristics of such solid-liquid suspensions. The investigated suspension electrode is an opaque slurry that consists of microscopic zinc particles and an aqueous potassium hydroxide electrolyte. Commonly, ultrasound Doppler velocimetry is used for flow imaging in opaque fluids. However, due to the high particle concentration in the suspension electrode, strong scattering and wavefront distortions of the ultrasound are introduced. In this paper, we show that this results in an increased measurement uncertainty for Doppler-based velocity estimation. Instead, ultrasound image velocimetry is applied to measure the 2-D and two-component flow field in the zinc-electrolyte suspension. This is possible by adapting the measurement system to the suspension with a calibration setup. The total measurement uncertainties of 4.1% and 2.5% for the axial and lateral flow components are derived from the calibration measurements. For the first time, the flow field of such a suspension could be measured in a scaled fluidic model of a ZAB. The comparison of the estimated flow rates from the velocity profiles showed good agreement to a gravimetric reference. A significant difference in the flow characteristics of a macroscopically homogeneous electrolyte and the same electrolyte loaded with 8 vol.-% zinc particles, i.e., the suspension electrode, was found. Along with the demonstration of the measurement technique for opaque, concentrated suspensions, the measurement data will be used to calibrate and validate numerical models for comparable multiphase fluids.

Ultrasonic measurements of the bulk flow field in foams.

The flow field of moving foams is relevant for basic research and for the optimization of industrial processes such as froth flotation. However, no adequate measurement technique exists for the local velocity distribution inside the foam bulk. We have investigated the ultrasound Doppler velocimetry (UDV), providing the first two-dimensional, non-invasive velocity measurement technique with an adequate spatial (10mm) and temporal resolution (2.5Hz) that is applicable to medium scale foam flows. The measurement object is dry aqueous foam flowing upward in a rectangular channel. An array of ultrasound transducers is mounted within the channel, sending pulses along the main flow axis, and receiving echoes from the foam bulk. This results in a temporally and spatially resolved, planar velocity field up to a measurement depth of 200mm, which is approximately one order of magnitude larger than those of optical techniques. A comparison with optical reference measurements of the surface velocity of the foam allows to validate the UDV results. At 2.5Hz frame rate an uncertainty below 15 percent and an axial spatial resolution better than 10mm is found. Therefore, UDV is a suitable tool for monitoring of industrial processes as well as the scientific investigation of three-dimensional foam flows on medium scales.

Flow Field Imaging With Ultrasonic Guided Waves for Exploring Metallic Melts.

Ultrasonic guided waves enable flow measurements under harsh conditions, which are important, for instance, to monitor and optimize industrial solidification processes. The usage of single mode waveguides overcomes the problem of overheating the transducers, but requires a mechanical scanning for imaging. A multimode waveguide can carry the information of an image, but a scrambling of the signals occurs due to multiple reflections at the waveguide's boundaries. We propose a new approach to overcome the scrambling and enable flow imaging through a short waveguide: the time-reversal virtual array (TRVA) method. The time invariance of the wave equation in a linear medium allows the refocusing on a limited set of calibrated points, which form the virtual array. This virtual array can conceptually be treated as a phased array. In this paper, the TRVA has been characterized theoretically, numerically, and experimentally. For the first time, a planar velocity measurement of a rotating flow in liquid gallium-indium-tin is demonstrated through a borosilicate waveguide at room temperature. A comparison with reference measurements showed good agreement.

Phased Array Ultrasound System for Planar Flow Mapping in Liquid Metals.

Controllable magnetic fields can be used to optimize flows in technical and industrial processes involving liquid metals in order to improve quality and yield. However, experimental studies in magnetohydrodynamics often involve complex, turbulent flows and require planar, two-component (2c) velocity measurements through only one acoustical access. We present the phased array ultrasound Doppler velocimeter as a modular research platform for flow mapping in liquid metals. It combines the pulse wave Doppler method with the phased array technique to adaptively focus the ultrasound beam. This makes it possible to resolve smaller flow structures in planar measurements compared with fixed-beam sensors and enables 2c flow mapping with only one acoustical access via the cross beam technique. From simultaneously measured 2-D velocity fields, quantities for turbulence characterization can be derived. The capabilities of this measurement system are demonstrated through measurements in the alloy gallium-indium-tin at room temperature. The 2-D, 2c velocity measurements of a flow in a cubic vessel driven by a rotating magnetic field (RMF) with a spatial resolution of up to 2.2 mm are presented. The measurement results are in good agreement with a semianalytical simulation. As a highlight, two-point correlation functions of the velocity field for different magnitudes of the RMF are presented.

Ultrasound Flow Mapping for the Investigation of Crystal Growth.

A high energy conversion and cost efficiency are keys for the transition to renewable energy sources, e.g., solar cells. The efficiency of multicrystalline solar cells can be improved by enhancing the understanding of its crystallization process, especially the directional solidification. In this paper, a novel measurement system for the characterization of flow phenomena and solidification processes in low-temperature model experiments on the basis of ultrasound (US) Doppler velocimetry is described. It captures turbulent flow phenomena in two planes with a frame rate of 3.5 Hz and tracks the shape of the solid-liquid interface during multihour experiments. Time-resolved flow mapping is performed using four linear US arrays with a total of 168 transducer elements. Long duration measurements are enabled through an online, field-programmable gate array (FPGA)-based signal processing. Nine single US transducers allow for in situ tracking of a solid-liquid interface. Results of flow and solidification experiments in the model experiment are presented and compared with numerical simulation. The potential of the developed US system for measuring turbulent flows and for tracking the solidification front during a directional crystallization process is demonstrated. The results of the model experiments are in good agreement with numerical calculations and can be used for the validation of numerical models, especially the selection of the turbulence model.