16 results
Search Results
Now showing 1 - 10 of 16
- 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.
- ItemA 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, MarianaEmbryo 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.
- 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
- ItemHuman spermbots for patient-representative 3D ovarian cancer cell treatment(Cambridge : RSC Publ., 2020) Xu, Haifeng; Medina-Sánchez, Mariana; Zhang, Wunan; Seaton, Melanie P. H.; Brison, Daniel R.; Edmondson, Richard J.; Taylor, Stephen S.; Nelson, Louisa; Zeng, Kang; Bagley, Steven; Ribeiro, Carla; Restrepo, Lina P.; Lucena, Elkin; Schmidt, Christine K.; Schmidt, Oliver G.Cellular micromotors are attractive for locally delivering high concentrations of drug, and targeting hard-to-reach disease sites such as cervical cancer and early ovarian cancer lesions by non-invasive means. Spermatozoa are highly efficient micromotors perfectly adapted to traveling up the female reproductive system. Indeed, bovine sperm-based micromotors have shown potential to carry drugs toward gynecological cancers. However, due to major differences in the molecular make-up of bovine and human sperm, a key translational bottleneck for bringing this technology closer to the clinic is to transfer this concept to human material. Here, we successfully load human sperm with Doxorubicin (DOX) and perform treatment of 3D cervical cancer and patient-representative ovarian cancer cell cultures, resulting in strong anticancer cell effects. Additionally, we define the subcellular localization of the chemotherapeutic drug within human sperm, using high-resolution optical microscopy. We also assess drug effects on sperm motility and viability over time, employing sperm samples from healthy donors as well as assisted reproduction patients. Finally, we demonstrate guidance and release of human drug-loaded sperm onto cancer tissues using magnetic microcaps, and show the sperm microcap loaded with a second anticancer drug, camptothecin (CPT), which unlike DOX is not suitable for directly loading into sperm due to its hydrophobic nature. This co-drug delivery approach opens up novel targeted combinatorial drug therapies for future applications. © 2020 The Royal Society of Chemistry.
- 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.
- ItemExperimental observation of Berry phases in optical Möbius-strip microcavities(London [u.a.] : Nature Publ. Group, 2022) Wang, Jiawei; Valligatla, Sreeramulu; Yin, Yin; Schwarz, Lukas; Medina-Sánchez, Mariana; Baunack, Stefan; Lee, Ching Hua; Thomale, Ronny; Li, Shilong; Fomin, Vladimir M.; Ma, Libo; Schmidt, Oliver G.The Möbius strip, a fascinating loop structure with one-sided topology, provides a rich playground for manipulating the non-trivial topological behaviour of spinning particles, such as electrons, polaritons and photons, in both real and parameter spaces. For photons resonating in a Möbius-strip cavity, the occurrence of an extra phase—known as the Berry phase—with purely topological origin is expected due to its non-trivial evolution in parameter space. However, despite numerous theoretical investigations, characterizing the optical Berry phase in a Möbius-strip cavity has remained elusive. Here we report the experimental observation of the Berry phase generated in optical Möbius-strip microcavities. In contrast to theoretical predictions in optical, electronic and magnetic Möbius-topology systems where only Berry phase π occurs, we demonstrate that a variable Berry phase smaller than π can be acquired by generating elliptical polarization of resonating light. Möbius-strip microcavities as integrable and Berry-phase-programmable optical systems are of great interest in topological physics and emerging classical or quantum photonic applications.
- ItemNano-biosupercapacitors enable autarkic sensor operation in blood([London] : Nature Publishing Group UK, 2021) Lee, Yeji; Bandari, Vineeth Kumar; Li, Zhe; Medina-Sánchez, Mariana; Maitz, Manfred F.; Karnaushenko, Daniil; Tsurkan, Mikhail V; Karnaushenko, Dmitriy D.; Schmidt, Oliver G.Today’s smallest energy storage devices for in-vivo applications are larger than 3 mm3 and lack the ability to continuously drive the complex functions of smart dust electronic and microrobotic systems. Here, we create a tubular biosupercapacitor occupying a mere volume of 1/1000 mm3 (=1 nanoliter), yet delivering up to 1.6 V in blood. The tubular geometry of this nano-biosupercapacitor provides efficient self-protection against external forces from pulsating blood or muscle contraction. Redox enzymes and living cells, naturally present in blood boost the performance of the device by 40% and help to solve the self-discharging problem persistently encountered by miniaturized supercapacitors. At full capacity, the nano-biosupercapacitors drive a complex integrated sensor system to measure the pH-value in blood. This demonstration opens up opportunities for next generation intravascular implants and microrobotic systems operating in hard-to-reach small spaces deep inside the human body.
- ItemShape-Controlled Flexible Microelectronics Facilitated by Integrated Sensors and Conductive Polymer Actuators(Weinheim : Wiley-VCH Verlag GmbH & Co. KGaA, 2021) Rivkin, Boris; Becker, Christian; Akbar, Farzin; Ravishankar, Rachappa; Karnaushenko, Dmitriy; Naumann, Ronald; Mirhajivarzaneh, Aaleh; Medina-Sánchez, Mariana; Karnaushenko, Daniil; Schmidt, Oliver G.The next generation of biomedical tools requires reshapeable electronics to closely interface with biological tissues. This will offer unique mechanical properties and the ability to conform to irregular geometries while being robust and lightweight. Such devices can be achieved with soft materials and thin-film structures that are able to reshape on demand. However, reshaping at the submillimeter scale remains a challenging task. Herein, shape-controlled microscale devices are demonstrated that integrate electronic sensors and electroactive polymer actuators. The fast and biocompatible actuators are capable of actively reshaping the device into flat or curved geometries. The curvature and position of the devices are monitored with strain or magnetic sensors. The sensor signals are used in a closed feedback loop to control the actuators. The devices are wafer-scale microfabricated resulting in multiple functional units capable of grasping, holding, and releasing biological tissues, as demonstrated with a neuronal bundle.
- 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.
- ItemSperm-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