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- ItemSperm 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.
- 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
- ItemBlood platelet enrichment in mass-producible surface acoustic wave (SAW) driven microfluidic chips(Cambridge : RSC, 2019) Richard, Cynthia; Fakhfouri, Armaghan; Colditz, Melanie; Striggow, Friedrich; Kronstein-Wiedemann, Romy; Tonn, Torsten; Medina-Sánchez, Mariana; Schmidt, Oliver G.; Gemming, Thomas; Winkler, AndreasThe ability to separate specific biological components from cell suspensions is indispensable for liquid biopsies, and for personalized diagnostics and therapy. This paper describes an advanced surface acoustic wave (SAW) based device designed for the enrichment of platelets (PLTs) from a dispersion of PLTs and red blood cells (RBCs) at whole blood concentrations, opening new possibilities for diverse applications involving cell manipulation with high throughput. The device is made of patterned SU-8 photoresist that is lithographically defined on the wafer scale with a new proposed methodology. The blood cells are initially focused and subsequently separated by an acoustic radiation force (ARF) applied through standing SAWs (SSAWs). By means of flow cytometric analysis, the PLT concentration factor was found to be 7.7, and it was proven that the PLTs maintain their initial state. A substantially higher cell throughput and considerably lower applied powers than comparable devices from literature were achieved. In addition, fully coupled 3D numerical simulations based on SAW wave field measurements were carried out to anticipate the coupling of the wave field into the fluid, and to obtain the resulting pressure field. A comparison to the acoustically simpler case of PDMS channel walls is given. The simulated results show an ideal match to the experimental observations and offer the first insights into the acoustic behavior of SU-8 as channel wall material. The proposed device is compatible with current (Lab-on-a-Chip) microfabrication techniques allowing for mass-scale, reproducible chip manufacturing which is crucial to push the technology from lab-based to real-world applications. © The Royal Society of Chemistry.
- ItemMagnetofluidic platform for multidimensional magnetic and optical barcoding of droplets(Cambridge : RSC, 2014) Lin, Gungun; Makarov, Denys; Medina-Sánchez, Mariana; Guix, Maria; Baraban, Larysa; Cuniberti, Gianaurelio; Schmidt, Oliver G.We present a concept of multidimensional magnetic and optical barcoding of droplets based on a magnetofluidic platform. The platform comprises multiple functional areas, such as an encoding area, an encoded droplet pool and a magnetic decoding area with integrated giant magnetoresistive (GMR) sensors. To prove this concept, penicillin functionalized with fluorescent dyes is coencapsulated with magnetic nanoparticles into droplets. While fluorescent dyes are used as conventional optical barcodes which are decoded with an optical decoding setup, an additional dimensionality of barcodes is created by using magnetic nanoparticles as magnetic barcodes for individual droplets and integrated micro-patterned GMR sensors as the corresponding magnetic decoding devices. The strategy of incorporating a magnetic encoding scheme provides a dynamic range of ~40 dB in addition to that of the optical method. When combined with magnetic barcodes, the encoding capacity can be increased by more than 1 order of magnitude compared with using only optical barcodes, that is, the magnetic platform provides more than 10 unique magnetic codes in addition to each optical barcode. Besides being a unique magnetic functional element for droplet microfluidics, the platform is capable of on-demand facile magnetic encoding and real-time decoding of droplets which paves the way for the development of novel non-optical encoding schemes for highly multiplexed droplet-based biological assays.
- 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.
- ItemSperm-Hybrid Micromotor for Targeted Drug Delivery(Washington, DC : Soc., 2017-12-13) Xu, Haifeng; Medina-Sánchez, Mariana; Magdanz, Veronika; Schwarz, Lukas; Hebenstreit, Franziska; Schmidt, Oliver G.A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm–cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.