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

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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.

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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

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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.

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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

DOI 10.3389/fspor.2023.1327792

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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

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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.

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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,

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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

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Toward More Inclusive Networks and Initiatives in Innovation Ecosystems: Protocol for a Systematic Review 

Expanding the cooperation and enlarging the participation of more diverse stakeholders within innovation ecosystems will increase their efficiency and capacity to contribute at local, regional, and national levels. This paper presents the protocol for a systematic review that will identify “opening-up” strategies of innovation ecosystems for increasing the participation of more diverse innovation stakeholders, particularly from low-innovation countries, during the ecosystem formation period.

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.

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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 

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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. 

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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.

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