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- ItemDual 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, MarianaThe 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
- ItemNanomaterial-decorated micromotors for enhanced photoacoustic imaging(Berlin ; Heidelberg : Springer, 2023) Aziz, Azaam; Nauber, Richard; Sánchez Iglesias, Ana; Tang, Min; Ma, Libo; Liz-Marzán, Luis M.; Schmidt, Oliver G.; Medina-Sánchez, MarianaMicro-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.
- ItemReal-Time IR Tracking of Single Reflective Micromotors through Scattering Tissues(Weinheim : Wiley-VCH, 2019) Aziz, Azaam; Medina-Sánchez, Mariana; Koukourakis, Nektarios; Wang, Jiawei; Kuschmierz, Robert; Radner, Hannes; Czarske, Jürgen W.; Schmidt, Oliver G.Medical micromotors have the potential to lead to a paradigm shift in future biomedicine, as they may perform active drug delivery, microsurgery, tissue engineering, or assisted fertilization in a minimally invasive manner. However, the translation to clinical treatment is challenging, as many applications of single or few micromotors require real-time tracking and control at high spatiotemporal resolution in deep tissue. Although optical techniques are a popular choice for this task, absorption and strong light scattering lead to a pronounced decrease of the signal-to-noise ratio with increasing penetration depth. Here, a highly reflective micromotor is introduced which reflects more than tenfold the light intensity of simple gold particles and can be precisely navigated by external magnetic fields. A customized optical IR imaging setup and an image correlation technique are implemented to track single micromotors in real-time and label-free underneath phantom and ex vivo mouse skull tissues. As a potential application, the micromotors speed is recorded when moving through different viscous fluids to determine the viscosity of diverse physiological fluids toward remote cardiovascular disease diagnosis. Moreover, the micromotors are loaded with a model drug to demonstrate their cargo-transport capability. The proposed reflective micromotor is suitable as theranostic tool for sub-skin or organ-on-a-chip applications. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
- ItemIRONSperm: Sperm-templated soft magnetic microrobots(Washington, DC : American Association for the Advancement of Science, 2020) Magdanz, Veronika; Khalil, Islam S.M.; Simmchen, Juliane; Furtado, Guilherme P.; Mohanty, Sumit; Gebauer, Johannes; Xu, Haifeng; Klingner, Anke; Aziz, Azaam; Medina-Sánchez, Mariana; Schmidt, Oliver G.; Misra, SarthakWe develop biohybrid magnetic microrobots by electrostatic self-assembly of nonmotile sperm cells and magnetic nanoparticles. Incorporating a biological entity into microrobots entails many functional advantages beyond shape templating, such as the facile uptake of chemotherapeutic agents to achieve targeted drug delivery. We present a single-step electrostatic self-assembly technique to fabricate IRONSperms, soft magnetic microswimmers that emulate the motion of motile sperm cells. Our experiments and theoretical predictions show that the swimming speed of IRONSperms exceeds 0.2 body length/s (6.8 ± 4.1 µm/s) at an actuation frequency of 8 Hz and precision angle of 45°. We demonstrate that the nanoparticle coating increases the acoustic impedance of the sperm cells and enables localization of clusters of IRONSperm using ultrasound feedback. We also confirm the biocompatibility and drug loading ability of these microrobots, and their promise as biocompatible, controllable, and detectable biohybrid tools for in vivo targeted therapy.
- ItemSelf-sufficient self-oscillating microsystem driven by low power at low Reynolds numbers(Washington, DC [u.a.] : American Association for the Advancement of Science, 2021) Akbar, Farzin; Rivkin, Boris; Aziz, Azaam; Becker, Christian; Karnaushenko, Dmitriy D.; Medina-Sánchez, Mariana; Karnaushenko, Daniil; Schmidt, Oliver G.Oscillations at several hertz are a key feature of dynamic behavior of various biological entities, such as the pulsating heart, firing neurons, or the sperm-beating flagellum. Inspired by nature’s fundamental self-oscillations, we use electroactive polymer microactuators and three-dimensional microswitches to create a synthetic electromechanical parametric relaxation oscillator (EMPRO) that relies on the shape change of micropatterned polypyrrole and generates a rhythmic motion at biologically relevant stroke frequencies of up to ~95 Hz. We incorporate an Ag-Mg electrochemical battery into the EMPRO for autonomous operation in a nontoxic environment. Such a self-sufficient self-oscillating microsystem offers new opportunities for artificial life at low Reynolds numbers by, for instance, mimicking and replacing nature’s propulsion and pumping units.