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Now showing 1 - 10 of 23
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    Sperm Micromotors for Cargo Delivery through Flowing Blood
    (Washington, DC : American Chemical Society, 2020) Xu, Haifeng; Medina-Sánchez, Mariana; Maitz, Manfred F.; Werner, Carsten; Schmidt, Oliver G.
    Micromotors are recognized as promising candidates for untethered micromanipulation and targeted cargo delivery in complex biological environments. However, their feasibility in the circulatory system has been limited due to the low thrust force exhibited by many of the reported synthetic micromotors, which is not sufficient to overcome the high flow and complex composition of blood. Here we present a hybrid sperm micromotor that can actively swim against flowing blood (continuous and pulsatile) and perform the function of heparin cargo delivery. In this biohybrid system, the sperm flagellum provides a high propulsion force while the synthetic microstructure serves for magnetic guidance and cargo transport. Moreover, single sperm micromotors can assemble into a train-like carrier after magnetization, allowing the transport of multiple sperm or medical cargoes to the area of interest, serving as potential anticoagulant agents to treat blood clots or other diseases in the circulatory system.
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    A Rotating Spiral Micromotor for Noninvasive Zygote Transfer
    (Hoboke, NJ : Wiley, 2020) Schwarz, Lukas; Karnaushenko, Dmitriy D.; Hebenstreit, Franziska; Naumann, Ronald; Schmidt, Oliver G.; Medina-Sánchez, Mariana
    Embryo transfer (ET) is a decisive step in the in vitro fertilization process. In most cases, the embryo is transferred to the uterus after several days of in vitro culture. Although studies have identified the beneficial effects of ET on proper embryo development in the earlier stages, this strategy is compromised by the necessity to transfer early embryos (zygotes) back to the fallopian tube instead of the uterus, which requires a more invasive, laparoscopic procedure, termed zygote intrafallopian transfer (ZIFT). Magnetic micromotors offer the possibility to mitigate such surgical interventions, as they have the potential to transport and deliver cellular cargo such as zygotes through the uterus and fallopian tube noninvasively, actuated by an externally applied rotating magnetic field. This study presents the capture, transport, and release of bovine and murine zygotes using two types of magnetic micropropellers, helix and spiral. Although helices represent an established micromotor architecture, spirals surpass them in terms of motion performance and with their ability to reliably capture and secure the cargo during both motion and transfer between different environments. Herein, this is demonstrated with murine oocytes/zygotes as the cargo; this is the first step toward the application of noninvasive, magnetic micromotor‐assisted ZIFT.
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    Advanced Hybrid GaN/ZnO Nanoarchitectured Microtubes for Fluorescent Micromotors Driven by UV Light
    (Weinheim : Wiley-VCH, 2020) Wolff, Niklas; Ciobanu, Vladimir; Enachi, Mihail; Kamp, Marius; Braniste, Tudor; Duppel, Viola; Shree, Sindu; Raevschi, Simion; Medina-Sánchez, Mariana; Adelung, Rainer; Schmidt, Oliver G.; Kienle, Lorenz; Tiginyanu, Ion
    The development of functional microstructures with designed hierarchical and complex morphologies and large free active surfaces offers new potential for improvement of the pristine microstructures properties by the synergistic combination of microscopic as well as nanoscopic effects. In this contribution, dedicated methods of transmission electron microscopy (TEM) including tomography are used to characterize the complex hierarchically structured hybrid GaN/ZnO:Au microtubes containing a dense nanowire network on their interior. The presence of an epitaxially stabilized and chemically extremely stable ultrathin layer of ZnO on the inner wall of the produced GaN microtubes is evidenced. Gold nanoparticles initially trigger the catalytic growth of solid solution phase (Ga1– xZnx)(N1– xOx) nanowires into the interior space of the microtube, which are found to be terminated by AuGa-alloy nanodots coated in a shell of amorphous GaOx species after the hydride vapor phase epitaxy process. The structural characterization suggests that this hierarchical design of GaN/ZnO microtubes could offer the potential to exhibit improved photocatalytic properties, which are initially demonstrated under UV light irradiation. As a proof of concept, the produced microtubes are used as photocatalytic micromotors in the presence of hydrogen peroxide solution with luminescent properties, which are appealing for future environmental applications and active matter fundamental studies. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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    Switching Propulsion Mechanisms of Tubular Catalytic Micromotors
    (Weinheim : Wiley-VCH, 2021) Wrede, Paul; Medina-Sánchez, Mariana; Fomin, Vladimir M.; Schmidt, Oliver G.
    Different propulsion mechanisms have been suggested for describing the motion of a variety of chemical micromotors, which have attracted great attention in the last decades due to their high efficiency and thrust force, enabling several applications in the fields of environmental remediation and biomedicine. Bubble-recoil based motion, in particular, has been modeled by three different phenomena: capillary forces, bubble growth, and bubble expulsion. However, these models have been suggested independently based on a single influencing factor (i.e., viscosity), limiting the understanding of the overall micromotor performance. Therefore, the combined effect of medium viscosity, surface tension, and fuel concentration is analyzed on the micromotor swimming ability, and the dominant propulsion mechanisms that describe its motion more accurately are identified. Using statistically relevant experimental data, a holistic theoretical model is proposed for bubble-propelled tubular catalytic micromotors that includes all three above-mentioned phenomena and provides deeper insights into their propulsion physics toward optimized geometries and experimental conditions.
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    Dual Ultrasound and Photoacoustic Tracking of Magnetically Driven Micromotors: From In Vitro to In Vivo
    (Weinheim : Wiley-VCH, 2021) Aziz, Azaam; Holthof, Joost; Meyer, Sandra; Schmidt, Oliver G.; Medina-Sánchez, Mariana
    The fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms has boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic imaging (PAI), considered a functional technique, has shown to be promising for the visualization of micromotors in deep tissue with high spatiotemporal resolution as it possesses the molecular specificity of optical methods and the penetration depth of ultrasound. However, the precise maneuvering and function's control of medical micromotors, in particular in living organisms, require both anatomical and functional imaging feedback. Therefore, herein, the use of high-frequency ultrasound and PAI is reported to obtain anatomical and molecular information, respectively, of magnetically-driven micromotors in vitro and under ex vivo tissues. Furthermore, the steerability of the micromotors is demonstrated by the action of an external magnetic field into the uterus and bladder of living mice in real-time, being able to discriminate the micromotors’ signal from one of the endogenous chromophores by multispectral analysis. Finally, the successful loading and release of a model cargo by the micromotors toward non-invasive in vivo medical interventions is demonstrated. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
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    Medical Imaging of Microrobots: Toward In Vivo Applications
    (Washington, DC : American Chemical Society, 2020) Aziz, Azaam; Pane, Stefano; Iacovacci, Veronica; Koukourakis, Nektarios; Czarske, Jürgen; Menciassi, Arianna; Medina-Sánchez, Mariana; Schmidt, Oliver G
    Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications.
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    Micromotor-mediated sperm constrictions for improved swimming performance
    (Berlin ; Heidelberg : Springer, 2021) Striggow, Friedrich; Nadporozhskaia, Lidiia; Friedrich, Benjamin M.; Schmidt, Oliver G.; Medina-Sánchez, Mariana
    Sperm-driven micromotors, consisting of a single sperm cell captured in a microcap, utilize the strong propulsion generated by the flagellar beat of motile spermatozoa for locomotion. It enables the movement of such micromotors in biological media, while being steered remotely by means of an external magnetic field. The substantial decrease in swimming speed, caused by the additional hydrodynamic load of the microcap, limits the applicability of sperm-based micromotors. Therefore, to improve the performance of such micromotors, we first investigate the effects of additional cargo on the flagellar beat of spermatozoa. We designed two different kinds of microcaps, which each result in different load responses of the flagellar beat. As an additional design feature, we constrain rotational degrees of freedom of the cell’s motion by modifying the inner cavity of the cap. Particularly, cell rolling is substantially reduced by tightly locking the sperm head inside the microcap. Likewise, cell yawing is decreased by aligning the micromotors under an external static magnetic field. The observed differences in swimming speed of different micromotors are not so much a direct consequence of hydrodynamic effects, but rather stem from changes in flagellar bending waves, hence are an indirect effect. Our work serves as proof-of-principle that the optimal design of microcaps is key for the development of efficient sperm-driven micromotors.
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    Impedimetric Microfluidic Sensor-in-a-Tube for Label-Free Immune Cell Analysis
    (Weinheim : Wiley-VCH, 2021) Egunov, Aleksandr I.; Dou, Zehua; Karnaushenko, Dmitriy D.; Hebenstreit, Franziska; Kretschmann, Nicole; Akgün, Katja; Ziemssen, Tjalf; Karnaushenko, Daniil; Medina-Sánchez, Mariana; Schmidt, Oliver G.
    Analytical platforms based on impedance spectroscopy are promising for non-invasive and label-free analysis of single cells as well as of their extracellular matrix, being essential to understand cell function in the presence of certain diseases. Here, an innovative rolled-up impedimetric microfulidic sensor, called sensor-in-a-tube, is introduced for the simultaneous analysis of single human monocytes CD14+ and their extracellular medium upon liposaccharides (LPS)-mediated activation. In particular, rolled-up platinum microelectrodes are integrated within for the static and dynamic (in-flow) detection of cells and their surrounding medium (containing expressed cytokines) over an excitation frequency range from 102 to 5 × 106 Hz. The correspondence between cell activation stages and the electrical properties of the cell surrounding medium have been detected by electrical impedance spectroscopy in dynamic mode without employing electrode surface functionalization or labeling. The designed sensor-in-a-tube platform is shown as a sensitive and reliable tool for precise single cell analysis toward immune-deficient diseases diagnosis.
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    Sperm-Driven Micromotors Moving in Oviduct Fluid and Viscoelastic Media
    (Weinheim : Wiley-VCH, 2020) Striggow, Friedrich; Medina-Sánchez, Mariana; Auernhammer, Günter K.; Magdanz, Veronika; Friedrich, Benjamin M.; Schmidt, Oliver G.
    Biohybrid micromotors propelled by motile cells are fascinating entities for autonomous biomedical operations on the microscale. Their operation under physiological conditions, including highly viscous environments, is an essential prerequisite to be translated to in vivo settings. In this work, a sperm-driven microswimmer, referred to as a spermbot, is demonstrated to operate in oviduct fluid in vitro. The viscoelastic properties of bovine oviduct fluid (BOF), one of the fluids that sperm cells encounter on their way to the oocyte, are first characterized using passive microrheology. This allows to design an artificial oviduct fluid to match the rheological properties of oviduct fluid for further experiments. Sperm motion is analyzed and it is confirmed that kinetic parameters match in real and artificial oviduct fluids, respectively. It is demonstrated that sperm cells can efficiently couple to magnetic microtubes and propel them forward in media of different viscosities and in BOF. The flagellar beat pattern of coupled as well as of free sperm cells is investigated, revealing an alteration on the regular flagellar beat, presenting an on–off behavior caused by the additional load of the microtube. Finally, a new microcap design is proposed to improve the overall performance of the spermbot in complex biofluids. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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    Engineering microrobots for targeted cancer therapies from a medical perspective
    (Berlin : Springer Nature, 2020) Schmidt, Christine K.; Medina-Sánchez, Mariana; Edmondson, Richard J.; Schmidt, Oliver G.
    Systemic chemotherapy remains the backbone of many cancer treatments. Due to its untargeted nature and the severe side effects it can cause, numerous nanomedicine approaches have been developed to overcome these issues. However, targeted delivery of therapeutics remains challenging. Engineering microrobots is increasingly receiving attention in this regard. Their functionalities, particularly their motility, allow microrobots to penetrate tissues and reach cancers more efficiently. Here, we highlight how different microrobots, ranging from tailor-made motile bacteria and tiny bubble-propelled microengines to hybrid spermbots, can be engineered to integrate sophisticated features optimised for precision-targeting of a wide range of cancers. Towards this, we highlight the importance of integrating clinicians, the public and cancer patients early on in the development of these novel technologies.