PUBLICATIONS
Clinically Ready Magnetic Microrobots for Targeted Therapies
Systemic drug administration often causes off-target effects limiting the efficacy of advanced therapies. Targeted drug delivery approaches increase local drug concentrations at the diseased site while minimizing systemic drug exposure. We present a magnetically guided microrobotic drug delivery system capable of precise navigation under physiological conditions. This platform integrates a clinical electromagnetic navigation system, a custom-designed release catheter, and a dissolvable capsule for accurate therapeutic delivery. In vitro tests showed precise navigation in human vasculature models, and in vivo experiments confirmed tracking under fluoroscopy and successful navigation in large animal models. The microrobot balances magnetic material concentration, contrast agent loading, and therapeutic drug capacity, enabling effective hosting of therapeutics despite the integration complexity of its components, offering a promising solution for precise targeted drug delivery.
Fabian C. Landers, Lukas Hertle, Vitaly Pustovalov, Derick Sivakumaran, Oliver Brinkmann, Kirstin Meiners, Pascal Theiler, Valentin Gantenbein, Andrea Veciana, Michael Mattmann, Silas Riss, Simone Gervasoni, Christophe Chautems, Hao Ye, Semih Sevim, Andreas D. Flouris, Josep Puigmartí-Luis, Tiago Sotto Mayor, Pedro Alves, Tessa Lühmann, Xiangzhong Chen, Nicole Ochsenbein, Ueli Moehrlen, Philipp Gruber, Miriam Weisskopf, Quentin Boehler, Salvador Pané, Bradley J. Nelson, https://doi.org/10.48550/arXiv.2501.11553
Read the article here: https://zenodo.org/records/14718243
Emerging Issues on Targeted Drug Delivery
Read the full book here: https://zenodo.org/records/14621049
Shape-Morphing in Oxide Ceramic Kirigami Nanomembranes
Interfacial strain engineering in ferroic nanomembranes can broaden the scope of ferroic nanomembrane assembly as well as facilitate the engineering of multiferroic-based devices with enhanced functionalities. Geometrical engineering in these material systems enables the realization of 3-D architectures with unconventional physical properties. Here, 3-D multiferroic architectures are introduced by incorporating barium titanate (BaTiO3, BTO) and cobalt ferrite (CoFe2O4, CFO) bilayer nanomembranes. Using photolithography and substrate etching techniques, complex 3-D microarchitectures including helices, arcs, and kirigami-inspired frames are developed. These 3-D architectures exhibit remarkable mechanical deformation capabilities, which can be attributed to the superelastic behavior of the membranes and geometric configurations. It is also demonstrated that dynamic shape reconfiguration of these nanomembrane architectures under electron beam exposure showcases their potential as electrically actuated microgrippers and for other micromechanical applications. This research highlights the versatility and promise of multi-dimensional ferroic nanomembrane architectures in the fields of micro actuation, soft robotics, and adaptive structures, paving the way for incorporating these architectures into stimulus-responsive materials and devices.
, , , , , , , , , , Shape-Morphing in Oxide Ceramic Kirigami Nanomembranes. Adv. Mater. 2024, 2404825. https://doi.org/10.1002/adma.202404825
Read the full article here: https://zenodo.org/records/14013341
Magnetically Guided Microcatheter for Targeted Injection of Magnetic Particle Swarms
The initial delivery of small-scale magnetic devices such as microrobots is a key, but often overlooked, aspect for their use in clinical applications. The deployment of these devices within the dynamic environment of the human body presents significant challenges due to their dispersion caused by circulatory flows. Here, a method is introduced to effectively deliver a swarm of magnetic nanoparticles in fluidic flows. This approach integrates a magnetically navigated robotic microcatheter equipped with a reservoir for storing the magnetic nanoparticles. The microfluidic flow within the reservoir facilitates the injection of magnetic nanoparticles into the fluid stream, and a magnetic field gradient guides the swarm through the oscillatory flow to a target site. The microcatheter and reservoir are engineered to enable magnetic steering and injection of the magnetic nanoparticles. To demonstrate this approach, experiments are conducted utilizing a spinal cord phantom simulating intrathecal catheter delivery for applications in the central nervous system. These results demonstrate that the proposed microcatheter successfully concentrates nanoparticles near the desired location through the precise manipulation of magnetic field gradients, offering a promising solution for the controlled deployment of untethered magnetic micro-/nanodevices within the complex physiological circulatory systems of the human body.
, , , , , , , , , , , , , , , , Magnetically Guided Microcatheter for Targeted Injection of Magnetic Particle Swarms. Adv. Sci. 2024, 2404061. https://doi.org/10.1002/advs.202404061
Read the full article here: https://zenodo.org/records/13735040
A Naturally Inspired Extrusion-Based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices
Soft materials play a crucial role in small-scale robotic applications by closely mimicking the complex motion and morphing behavior of organisms. However, conventional fabrication methods face challenges in creating highly integrated small-scale soft devices. In this study, microfluidics is leveraged to precisely control reaction-diffusion (RD) processes to generate multifunctional and compartmentalized calcium-cross-linkable alginate-based microfibers. Under RD conditions, sophisticated alginate-based fibers are produced for magnetic soft continuum robotics applications with customizable features, such as geometry (compact or hollow), degree of cross-linking, and the precise localization of magnetic nanoparticles (inside the core, surrounding the fiber, or on one side). This fine control allows for tuning the stiffness and magnetic responsiveness of the microfibers. Additionally, chemically cleavable regions within the fibers enable disassembly into smaller robotic units or roll-up structures under a rotating magnetic field. These findings demonstrate the versatility of microfluidics in processing highly integrated small-scale devices.
, , , , , , , , , , , , , , A Naturally Inspired Extrusion-Based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices. Adv. Mater. 2024, 36, 2402309. https://doi.org/10.1002/adma.202402309
Read the full article here: https://zenodo.org/records/11500646
A Human-Scale Clinically Ready Electromagnetic Navigation System for Magnetically Responsive Biomaterials and Medical Devices
Magnetic navigation systems are used to precisely manipulate magnetically responsive materials enabling the realization of new minimally invasive procedures using magnetic medical devices. Their widespread applicability has been constrained by high infrastructure demands and costs. The study reports on a portable electromagnetic navigation system, the Navion, which is capable of generating a large magnetic field over a large workspace. The system is easy to install in hospital operating rooms and transportable through health care facilities, aiding in the widespread adoption of magnetically responsive medical devices. First, the design and implementation approach for the system are introduced and its performance is characterized. Next, in vitro navigation of different microrobot structures is demonstrated using magnetic field gradients and rotating magnetic fields. Spherical permanent magnets, electroplated cylindrical microrobots, microparticle swarms, and magnetic composite bacteria-inspired helical structures are investigated. The navigation of magnetic catheters is also demonstrated in two challenging endovascular tasks: 1) an angiography procedure and 2) deep navigation within the circle of Willis. Catheter navigation is demonstrated in a porcine model in vivo to perform an angiography under magnetic guidance.
S. Gervasoni, N. Pedrini, T. Rifai, C. Fischer, F. C. Landers, M. Mattmann, R. Dreyfus, S. Viviani, A. Veciana, E. Masina, B. Aktas, J. Puigmartí-Luis, C. Chautems, S. Pané, Q. Boehler, P. Gruber, B. J. Nelson, A Human-Scale Clinically Ready Electromagnetic Navigation System for Magnetically Responsive Biomaterials and Medical Devices. Adv. Mater. 2024, 2310701 https://doi.org/10.1002/adma.202310701
Read the full article here: https://zenodo.org/records/11501579
Single-Step Synthesis of Sub-10 nm Magnetic Nanoparticles with High Saturation Magnetization and Broad pH Stability
Iron oxide nanoparticles hold great potential for future biomedical applications but, to date, usually suffer from reduced magnetic properties compared to their bulk counterparts. The replacement of Fe(III) ions with Zn(II) ions can enhance their magnetic properties while keeping their biocompatibility characteristics. Yet, common synthesis methods for these highly magnetic particles require using environmentally harmful solvents, multiple steps, and postfunctionalization, all while being affected by poor scalability and high polydispersity. To address these challenges, in this study, a single-step coprecipitation-based method is developed to fabricate gelatin-coated, zinc-substituted, sub-10 nm-sized iron oxide nanoparticles exhibiting high saturation magnetization. This single-step synthesis benefits from simplicity and robustness, capable of yielding large amounts of highly magnetic nanoparticles without the utilization of environmentally harmful or highly toxic reagents. Furthermore, in situ gelatin coating during the synthesis ensures particle stability in aqueous solutions over a wide range of pH and enhances cell compatibility. Systematic investigations show a direct correlation between the particles’ magnetization and the concentrations of Zn(II) and NaOH, where particles with a zinc-to-iron ratio of Zn:Fe = 0.18:2.82 reach a maximum saturation magnetization of 91.2 emu g−1. Thus, these particles are promising candidates for biomedical applications.
Pustovalov, V., Landers, F.C., Hertle, L., Ko, H., Llacer-Wintle, J., Ye, H., Veciana, A., Franco, C., Sanchis-Gual, R., Chen, X.-Z., Pellicer, E., Puigmartí-Luis, J., Nelson, B.J. and Pané, S. (2024), Single-Step Synthesis of Sub-10 nm Magnetic Nanoparticles with High Saturation Magnetization and Broad pH Stability. Adv. Eng. Mater., 26: 2400307. https://doi.org/10.1002/adem.202400307
Read the full article here: https://zenodo.org/records/14039462
Patient-specific placental vessel segmentation with limited data
A major obstacle in applying machine learning for medical fields is the disparity between the data distribution of the training images and the data encountered in clinics. This phenomenon can be explained by inconsistent acquisition techniques and large variations across the patient spectrum. The result is poor translation of the trained models to the clinic, which limits their implementation in medical practice. Patient-specific trained networks could provide a potential solution. Although patient-specific approaches are usually infeasible because of the expenses associated with on-the-fly labeling, the use of generative adversarial networks enables this approach. This study proposes a patient-specific approach based on generative adversarial networks. In the presented training pipeline, the user trains a patient-specific segmentation network with extremely limited data which is supplemented with artificial samples generated by generative adversarial models. This approach is demonstrated in endoscopic video data captured during fetoscopic laser coagulation, a procedure used for treating twin-to-twin transfusion syndrome by ablating the placental blood vessels. Compared to a standard deep learning segmentation approach, the pipeline was able to achieve an intersection over union score of 0.60 using only 20 annotated images compared to 100 images using a standard approach. Furthermore, training with 20 annotated images without the use of the pipeline achieves an intersection over union score of 0.30, which, therefore, corresponds to a 100% increase in performance when incorporating the pipeline. A pipeline using GANs was used to generate artificial data which supplements the real data, this allows patient-specific training of a segmentation network. We show that artificial images generated using GANs significantly improve performance in vessel segmentation and that training patient-specific models can be a viable solution to bring automated vessel segmentation to the clinic.
Sarwin, G., Lussi, J., Gervasoni, S. et al. Patient-specific placental vessel segmentation with limited data. J Robotic Surg 18, 237 (2024). https://doi.org/10.1007/s11701-024-01981-z
Read the full article here: https://zenodo.org/records/15043820
3D Motion Manipulation for Micro- and Nanomachines: Progress and Future Directions
In the past decade, micro- and nanomachines (MNMs) have made outstanding achievements in the fields of targeted drug delivery, tumor therapy, microsurgery, biological detection, and environmental monitoring and remediation. Researchers have made significant efforts to accelerate the rapid development of MNMs capable of moving through fluids by means of different energy sources (chemical reactions, ultrasound, light, electricity, magnetism, heat, or their combinations). However, the motion of MNMs is primarily investigated in confined two-dimensional (2D) horizontal setups. Furthermore, three-dimensional (3D) motion control remains challenging, especially for vertical movement and control, significantly limiting its potential applications in cargo transportation, environmental remediation, and biotherapy. Hence, an urgent need is to develop MNMs that can overcome self-gravity and controllably move in 3D spaces. This review delves into the latest progress made in MNMs with 3D motion capabilities under different manipulation approaches, discusses the underlying motion mechanisms, explores potential design concepts inspired by nature for controllable 3D motion in MNMs, and presents the available 3D observation and tracking systems..
H. Huang, S. Yang, Y. Ying, X. Chen, J. Puigmartí-Luis, L. Zhang, S. Pané, 3D Motion Manipulation for Micro- and Nanomachines: Progress and Future Directions. Adv. Mater. 2024, 36, 2305925. https://doi.org/10.1002/adma.202305925
Read the full article here: https://zenodo.org/records/10651024
Dexterous helical magnetic robot for improved endovascular access
Treating vascular diseases in the brain requires access to the affected region inside the body. This is usually accomplished through a minimally invasive technique that involves the use of long, thin devices, such as wires and tubes, that are manually maneuvered by a clinician within the bloodstream. By pushing, pulling, and twisting, these devices are navigated through the tortuous pathways of the blood vessels. The outcome of the procedure heavily relies on the clinician’s skill and the device’s ability to navigate to the affected target region in the bloodstream, which is often inhibited by tortuous blood vessels. Sharp turns require high flexibility, but this flexibility inhibits translation of proximal insertion to distal tip advancement. We present a highly dexterous, magnetically steered continuum robot that overcomes pushability limitations through rotation. A helical protrusion on the device’s surface engages with the vessel wall and translates rotation to forward motion at every point of contact. An articulating magnetic tip allows for active steerability, enabling navigation from the aortic arch to millimeter-sized arteries of the brain. The effectiveness of the magnetic continuum robot has been demonstrated through successful navigation in models of the human vasculature and in blood vessels of a live pig.
Dreyfus R, Boehler Q, Lyttle S, Gruber P, Lussi J, Chautems C, Gervasoni S, Berberat J, Seibold D, Ochsenbein-Kölble N, Reinehr M, Weisskopf M, Remonda L, Nelson BJ. Dexterous helical magnetic robot for improved endovascular access. 2024 Feb ETH Research Collection https://doi.org/10.3929/ethz-b-000659728
Read the full article here: https://zenodo.org/records/10813540
On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines
Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure’s motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.
F. C. Landers, V. Gantenbein, L. Hertle, A. Veciana, J. Llacer-Wintle, X.-Z. Chen, H. Ye, C. Franco, J. Puigmartí-Luis, M. Kim, B. J. Nelson, S. Pané, “On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines. Adv. Mater. 2023, 2310084. https://doi.org/10.1002/adma.202310084
Read the full article here: https://zenodo.org/records/10549393
Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights
In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes’ performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.
Spanakis Marios, Fragkiadaki Persefoni, Renieri Elisavet, Vakonaki Elena, Fragkiadoulaki Irene, Alegakis Athanasios, Kiriakakis Mixalis, Panagiotou Nikolaos, Ntoumou Eleni, Gratsias Ioannis, Zoubaneas Evangelos, Morozova Galina Dmitrievna, Ovchinnikova Marina Alekseevna, Tsitsimpikou Christina, Tsarouhas Konstantinos, Drakoulis Nikolaos, Skalny Anatoly Viktorovich, Tsatsakis Aristides, Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights. Frontiers in Sports and Active Living. 2024 Jan;2024
Read the full article here: https://zenodo.org/records/10813025
A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle‑aged rats
Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging-related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18-month-old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre-treatment levels. TL was determined using the Q-FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI-1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle-aged rats, indicating a potential role of this formula in the prevention and treatment of aging-related diseases.
Tsatsakis A, Renieri E, Tsoukalas D, Buga AM, Sarandi E, Vakonaki E, Fragkiadaki P, Alegakis A, Nikitovic D, Calina D, Spandidos DA, Docea AO. A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle‑aged rats. Mol Med Rep. 2023 Dec;28(6):232. doi: 10.3892/mmr.2023.13119
Read the full article here: https://zenodo.org/records/10776679
3D Printed Template-Assisted Casting of Biocompatible Polyvinyl Alcohol-Based Soft Microswimmers with Tunable Stability
The past decade has seen an upsurge in the development of small-scale magnetic robots for various biomedical applications. However, many of the reported designs comprise components with biocompatibility concerns. Strategies for fabricating biocompatible and degradable microrobots are required. In this study, polyvinyl alcohol (PVA)-based magnetic hydrogel microrobots with different morphologies and tunable stability are developed by combining a 3D printed template-assisted casting with a salting-out process. 3D sacrificial micromolds are prepared via direct laser writing to shape PVA-magnetic nanoparticle composite hydrogel microrobots with high architectural complexity. By adjusting the PVA composition and salting-out parameters, the hydrogel dissolubility can be customized. Due to their high mobility, tunable stability, and high biocompatibility, these PVA-based magnetic microrobots are suitable platforms for targeted drug and cell delivery.
Sanchis-Gual, R., Ye, H., Ueno, T., Landers, F. C., Hertle, L., Deng, S., Veciana, A., Xia, Y., Franco, C., Choi, H., Puigmartí-Luis, J., Nelson, B. J., Chen, X.-Z., & Pané, S. (2023). 3D Printed Template-Assisted Casting of Biocompatible Polyvinyl Alcohol-Based Soft Microswimmers with Tunable Stability. https://doi.org/10.1002/adfm.202212952
Read the full article here: https://zenodo.org/records/10550966
Site-specific PEGylation of recombinant tissue-type plasminogen activator
Τissue-type plasminogen activator (tPA) is the gold standard for emergency treatment of ischemic stroke, which is the third leading cause of death worldwide. Major challenges of tPA therapy are its rapid elimination by plasminogen activator inhibitor-1 (PAI-1) and hepatic clearance, leading to the use of high doses and consequent serious side effects, including internal bleeding, swelling and low blood pressure. In this regard, we developed three polyethylene glycol (PEG)ylated tPA bioconjugates based on the recombinant human tPA drug Alteplase using site-specific conjugation strategies. The first bioconjugate with PEGylation at the N-terminus of tPA performed by reductive alkylation showed a reduced proteolytic activity of 68 % compared to wild type tPA. PEGylation at the single-free cysteine of tPA with linear and branched PEG revealed similar proteolytic activities as the wild-type protein. Moreover, both bioconjugates with PEG-cysteine-modification showed 2-fold slower inhibition kinetics by PAI-1. All bioconjugates increased in hydrodynamic size as a critical requirement for half-life extension.
Kirstin Meiners, Prisca Hamm, Marcus Gutmann, Jan Niedens, Agnieszka Nowak-Król, Salvador Pané, Tessa Lühmann, Site-specific PEGylation of recombinant tissue-type plasminogen activator, European Journal of Pharmaceutics and Biopharmaceutics, https://doi.org/10.1016/j.ejpb.2023.09.017
Read the full article here: https://zenodo.org/records/10550854
Simultaneous Localization and Actuation Using Electromagnetic Navigation Systems
Remote magnetic navigation provides a promising approach for improving the maneuverability and safety of surgical tools, such as catheters and endoscopes, in complex anatomies. The lack of existing localization systems compatible with this modality, beyond fluoroscopy and its harmful ionizing radiation, impedes its translation to clinical practice. To address this challenge, we propose a localization method that achieves full pose estimation by superimposing oscillating magnetic fields for localization onto actuation fields generated by an electromagnetic navigation system. The resulting magnetic field is measured using a three-axis magnetic field sensor embedded in the magnetic device to be localized. The method is evaluated on a three-coil system, and simultaneous actuation and localization is demonstrated with a magnetic catheter prototype with a Hall-effect sensor embedded at its tip. We demonstrate position estimation with mean accuracy and precision below 1 mm, and orientation estimation with mean errors below 2 deg at 10 Hz in a workspace of 80 x 80 x 60 mm. This contribution aims to advance the clinical adoption of remote magnetic navigation in minimally invasive surgery.
D. v. Arx, C. Fischer, H. Torlakcik, S. Pané, B. J. Nelson and Q. Boehler, “Simultaneous Localization and Actuation Using Electromagnetic Navigation Systems,” in IEEE Transactions on Robotics https://doi.org/10.3929/ethz-b-000646580
Read the full article here: https://zenodo.org/records/10651114
Toward More Inclusive Networks and Initiatives in Innovation Ecosystems: Protocol for a Systematic Review
Georgia Ntina, Eirini Mavromanolaki, & Andreas D Flouris. (2022). Toward More Inclusive Networks and Initiatives in Innovation Ecosystems: Protocol for a Systematic Review. JMIR Research Protocols. https://doi.org/10.2196/34071
Read the full article here: https://zenodo.org/records/7472619
Magnetically Guided Laser Surgery for the Treatment of Twin-to-Twin Transfusion Syndrome
Twin-to-twin transfusion syndrome (TTTS) is a severe disorder that often leads to the death of monochorionic twin fetuses, if left untreated. Current prenatal interventions to treat the condition involve the use of rigid fetoscopes for targeted laser coagulation of the vascular anastomoses. These tools are limited in their area of operation, making treatment challenging, especially in cases with anterior placentation. Herein, a robotic platform to perform this task using remote magnetic navigation is proposed. In contrast to rigid tools, the presented custom magnetic fetoscope is highly flexible, dexterous, and has considerable advantages, including safety and precision. A visual servoing algorithm that allows the surgeon to navigate in the uterus with submillimeter precision is introduced. The system has been validated on ex vivo human placentas in a setting that mimics the real intraoperative conditions.
Lussi, J., Gervasoni, S., Mattille, M., Dreyfus, R., Boehler, Q., Reinehr, M., Ochsenbein, N., Nelson, B. J., & Moehrlen, U. (2022). Magnetically Guided Laser Surgery for the Treatment of Twin-to-Twin Transfusion Syndrome. Στο Advanced Intelligent Systems https://doi.org/10.1002/aisy.202200182
Read the full article here: https://zenodo.org/records/10548936
Magnetically Assisted Robotic Fetal Surgery for the Treatment of Spina Bifida
Spina bifida is a congenital defect that occurs on the vertebral spine of a fetus. The most severe form causes exposure of the spinal cord and spinal nerve and has important repercussions on the life of the newborn child. Current prenatal operative procedures require laparotomy of the abdomen as well as hysterotomy of the uterus, which can result in severe consequences and risks for the mother. Here, we propose a robotically assisted endoscopic procedure based on magnetically steerable catheters to treat spina bifida defects in a minimally invasive way. The procedure can be performed in a fully remote manner using magnetic guidance and a haptic controller. Four custom magnetic catheter designs are presented to image, sever, grasp and close the lesion on the fetus back. We demonstrate our approach in vitro using phantom models of the abdomen, the uterus, and the defected fetus.
Simone Gervasoni, Jonas Lussi, Silvia Viviani, Quentin Boehler, Nicole Ochsenbein, Ueli Moehrlen, & Bradley J. Nelson. (2022). Magnetically Assisted Robotic Fetal Surgery for the Treatment of Spina Bifida. IEEE Transactions on Medical Robotics and Bionics. https://doi.org/10.1109/TMRB.2022.3146351
Read the full article here: https://zenodo.org/records/7472665
Powering and Fabrication of Small-Scale Robotics Systems
Purpose of Review: The increasing number of contributions in the feld of small-scale robotics is signifcantly associated with the progress in material science and process engineering during the last half century. With the objective of integrating the most optimal materials for the propulsion of these motile micro- and nanosystems, several manufacturing strategies have been adopted or specifcally developed. This brief review covers some recent advances in materials and fabrication of small-scale robots with a focus on the materials serving as components for their motion and actuation.
Recent Findings: Integration of a wealth of materials is now possible in several micro- and nanorobotic designs owing to the advances in micro- and nanofabrication and chemical synthesis. Regarding light-driven swimmers, novel photocatalytic materials and deformable liquid crystal elastomers have been recently reported. Acoustic swimmers are also gaining attention, with several prominent examples of acoustic bubble-based 3D swimmers being recently reported. Magnetic microand nanorobots are increasingly investigated for their prospective use in biomedical applications. The adoption of diferent materials and novel fabrication strategies based on 3D printing, template-assisted electrodeposition, or electrospinning is briefy discussed.
Summary: A brief review on fabrication and powering of small-scale robotics is presented. First, a concise introduction to the world of small-scale robotics and their propulsion by means of magnetic felds, ultrasound, and light is provided. Recent examples of materials and fabrication methodologies for the realization of these devices follow thereafter .
Salvador Pané, Pedro Wendel‑Garcia, Yonca Belce, Xiang‑Zhong Chen, & Josep Puigmartí‑Luis. (2021). Powering and Fabrication of Small-Scale Robotics Systems. NANOROBOTICS AND MICROROBOTICS. https://doi.org/10.1007/s43154-021-00066-1
Read the full article here: https://zenodo.org/records/7472624
Evolution, gaps, and trends in the origins of innovation ecosystems
The “innovation ecosystem” is an umbrella term used to account for the common efforts of different stakeholders to achieve innovation. Suppliers provide key parts and technologies that are complemented by products and services provided by a variety of other actors, while customers establish demand and capabilities. In this process of joint value creation, companies gain a competitive advantage by appreciating the overall value of the products and services delivered to customers. Themes including the cooperation between actors, the creation and acquisition of value by organizations, and ecosystem leadership have received increasing interest from both practitioners and scholars. Nevertheless, many knowledge gaps remain and there is urgent need to increase our understanding regarding the formation of innovation ecosystems. Although the genesis of innovation ecosystems has received limited attention to date, it has significant impact not only for research and practice, but also for policies aiming to promote the economic welfare of sectors, regions, and countries. It is crucial to understand the process of innovation ecosystem formation, because this period of ecosystem evolution is the most fragile. Therefore, external provision of the necessary conditions, resources, and activities during this period will have the highest impact. We are conducting a systematic review to understand the origins of innovation ecosystems, as well as the evolution, gaps, and trends associated with this process. Following PRISMA guidelines, we are searching the ISI Web of Science from database inception to Sept 1, 2021, for relevant studies. No restrictions on language or study design have been applied. Risk of bias, data extraction, and sensitivity analysis are being performed by two independent investigators. This talk presents the results from this work in an effort to increase our understanding regarding the formation of innovation ecosystems.
Read the full article: doi:10.18332/pht/142303
Magnetic small-scale robots: Principles, applications and challenges
Last two decades has seen a growth of the research on untethered mobile small-scale robots. These motile devices display the ability to travel through fluids by transforming the energy generated by an external power source into mechanical motion. As a result, these devices are being recognized as promising platforms to break through the drawbacks of nanoparticle drug delivery systems. Among the family of small-scale devices, magnetic micro- and nanorobots, which refer to those devices wirelessly controlled by external magnetic fields, are arguably the most appealing systems for biomedical applications. Magnetic fields display biocompatibility characteristics in a wide range of conditions, and they can penetrate body tissues with minimal interaction. Additionally, magnetic fields can be generated in several forms (rotating, oscillating, gradients), enabling a rich collection of motion mechanisms, including several that mimic those of cells and microorganisms. In the present talk, we will introduce magnetic small-scale robots, their actuation principles, designs and constituent materials. Next, we will discuss about existing and potential applications in the biomedical area. Finally, we will conclude with remaining challenges for their translation into clinical applications, with a special focus in the area of intravascular drug delivery.
Read the full article: doi:10.18332/pht/142290
Marrying inorganics and biologics: Opportunities and challenges
Stroke is the second leading cause of death worldwide. The gold standard for the emergency treatment of ischemic stroke is recombinant tissue plasminogen activator (tPA). However, its use is associated with serious side effects e.g. internal bleeding, which drives the effort for the development of targeted tPA delivery platforms. Some of the most promising active delivery strategies encompass the use of microdevices based on inorganic materials. Despite the promise of achieving synergistic effects, the consequences of the interactions between complex biological molecules and inorganic materials need careful investigation. Among them is the unspecific adsorption of tPA to inorganic surfaces. Co-incubation of nanoparticles and tPA lead to a reduction in enzyme recovery as investigated by SDS gel electrophoresis. Interestingly application of a fluorescence activity assay showed that at least part of the adsorbed enzyme retained its catalytic activity of 58% +/-3%. These findings have two-fold implications for future development of tPA associated microdevices. On one side their interactions could be monitored and optimized by surface treatments to achieve minimal adsorption and inactivation. On the other side adsorption of the active molecule could be employed for site-specific delivery with release kinetics determined by physiochemical interactions.
Read the full article: doi:10.18332/pht/142300
In flow controlled synthesis of blood clots
Nanoscience is one of the most developed fields in today’s world. Its applications cover examples in natural, physical, pharmacological, and chemical sciences, with a high impact on human advancement in the present and the future. The application of nanotechnologies includes several advantages, for example, the decrease of manufacturing costs, the development of new technologies based on new properties, and the mitigation of side effects on human and environmental health.
A stroke is a medical condition where poor blood flow causes the cell’s death because of a cerebrovascular or cardiovascular blockage. Strokes have been reported as one of the primary causes of death in 2019, with a 22% increase since the beginning of this century. This condition was responsible for 8.9 million deaths in 2019, with an expected increase, consequence of its relationship with the SARS-COV-2 (COVID19) virus1. Its high impact in human health has pushed scientists to develop and improve technologies for the study and treatment of strokes, as well as the relationship between stroke and viral diseases2-4. Current treatments for the disease have not overcome the medical limitations, where the administration times, drug efficiency, complex medical interventions, and secondary effects (such as haemorrhage) are liable for causing deaths among the treated people5. In this context, nanoscience concepts such as Lab-On-A-Chip technologies, controlled drug carrier transport, and micro-particle synthesis and manipulation can serve as a tool to overcome current challenges in stroke therapy. In this contribution, we will show how microfluidic technologies can have a great impact on this field enabling a controlled localization of clots as well as the study of their dissolution.
Read the full article: doi:10.18332/pht/142302
Microfluidic technologies for chemistry, materials science and biotechnology
Self-assembly has long being used to control covalent and non-covalent interactions where molecular design has been the major driving force to achieve a desired outcome. Like in nature, a full control over self-assembly processes could lead to rationalized structure-property correlations, a long-time sought in chemistry, materials science and biotechnology. However, the pathways followed and the mechanisms underlying the formation of supramolecular aggregates are still largely unknown and unresolved. Additionally, the effective integration of supramolecular matter into small-scale robots for controlled drug delivery applications is yet in its infancy. Accordingly, it is highly required to find new technologies that can allow to overcome all these challenges.
In this contribution, I will present how microfluidic devices can be used to uncover pathway complexity as well as to asses drug delivery applications with small-scale robots. Specifically, I will show that microfluidic technologies provide an unprecedented kinetic control over self-assembly processes; for example, enabling the isolation of well-defined kinetically trapped states as well as unprecedented metastable intermediates. Moreover, I will show that microfluidic conditions can also be used as a phantom environment to test drug delivery applications of rationally designed small-scale swimmers.
Read the full article: doi:10.18332/pht/142301
Soft-hard magnetically driven microrobotic devices
Magnetic micro- and nanorobots are promising candidates for the delivery of therapeutic agents in difficult-to-reach locations of the human body. These devices can swim through fluids by means of external magnetic fields. Depending on the specific design, these devices can exhibit a plethora of motion patterns as a function of the applied magnetic field. Many of these devices can also mimic the motion strategies of small organisms and cells. The vast majority of magnetic micro – and nanorobots are constructed either with magnetic hard blocks, or soft magnetic polymer nanocomposites. The first type usually comprises materials with poor biocompatibility characteristics (except for fully iron devices and few iron alloys), limited motion versatility and mechanical features far from those of biological tissues. The second, while being more versatile and adaptable in terms of motion and shape, and more similar to tissues in terms of their mechanical properties, are limited in terms of magnetic force. To overcome these limitations, devices that marry the excellent magnetic performance of magnetic hard components with the advantageous properties of soft polymeric materials for biomedicine should be developed. In this talk, we will showcase a strategy to produce microrobotic devices that comprise interlocked metallic and polymeric parts. The devices are constructed by means of template-assisted 3D printing by combining electrodeposition and mold-casting. We will demonstrate the richness of these devices in terms of motion. Finally, we will mention the potential applications of these machines for intravascular applications.
Read the full article: DOI: https://doi.org/10.18332/pht/142296
In Vitro Navigation of a Magnetic Sphere Using a Model Predictive Controller for Neurovascular Targeted Drug Delivery Applications
In this work, we focused on magnetic navigation inside a two-dimensional (2D) model of the main vasculature of the human brain (namely the circle of Willis). We manipulated a small-scaled untethered magnetic sphere inside an electromagnetic navigation system (eMNS), consisting of eight electromagnets to show remote magnetic navigation.
Read the full article: file:///C:/Users/User/Downloads/EasyChair-Preprint-8156.pdf
