An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses.

Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.

Learning to Control a Three-Dimensional Ferrofluidic Robot.

In recent years, ferrofluids have found increased popularity as a material for medical applications, such as ocular surgery, gastrointestinal surgery, and cancer treatment, among others. Ferrofluidic robots are multifunctional and scalable, exhibit fluid properties, and can be controlled remotely; thus, they are particularly advantageous for such medical tasks. Previously, ferrofluidic robot control has been achieved via the manipulation of handheld permanent magnets or in current-controlled electromagnetic fields resulting in two-dimensional position and shape control and three-dimensional (3D) coupled position-shape or position-only control. Control of ferrofluidic liquid droplet robots poses a unique challenge where model-based control has been shown to be computationally limiting. Thus, in this study, a model-free control method is chosen, and it is shown that the task of learning optimal control parameters for ferrofluidic robot control can be performed using machine learning. Particularly, we explore the use of Bayesian optimization to find optimal controller parameters for 3D pose control of a ferrofluid droplet: its centroid position, stretch direction, and stretch radius. We demonstrate that the position, stretch direction, and stretch radius of a ferrofluid droplet can be independently controlled in 3D with high accuracy and precision, using a simple control approach. Finally, we use ferrofluidic robots to perform pick-and-place, a lab-on-a-chip pH test, and electrical switching, in 3D settings. The purpose of this research is to expand the potential of ferrofluidic robots by introducing full pose control in 3D and to showcase the potential of this technology in the areas of microassembly, lab-on-a-chip, and electronics. The approach presented in this research can be used as a stepping-off point to incorporate ferrofluidic robots toward future research in these areas.

Magnetic Control of Protein Expression via Magneto-mechanical Actuation of ND-PEGylated Iron Oxide Nanocubes for Cell Therapy.

Engineered cells used as smart vehicles for delivery of secreted therapeutic proteins enable effective treatment of cancer and certain degenerative, autoimmune, and genetic disorders. However, current cell-based therapies use mostly invasive tools for tracking proteins and do not allow for controlled secretion of therapeutic proteins, which could result in unconstrained killing of surrounding healthy tissues or ineffective killing of host cancer cells. Regulating the expression of therapeutic proteins after success of therapy remains elusive. In this study, a noninvasive therapeutic approach mediated by magneto-mechanical actuation (MMA) was developed to remotely regulate the expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein, which is secreted by transduced cells. Stem cells, macrophages, and breast cancer cells were transduced with a lentiviral vector encoding the SGpL2TR protein. SGpL2TR comprises TRAIL and GpLuc domains optimized for cell-based applications. Our approach relies on the remote actuation of cubic-shape highly magnetic field responsive superparamagnetic iron oxide nanoparticles (SPIONs) coated with nitrodopamine PEG (ND-PEG), which are internalized within the cells. Cubic ND-PEG-SPIONs actuated by superlow frequency alternating current magnetic fields can translate magnetic forces into mechanical motion and in turn spur mechanosensitive cellular responses. Cubic ND-PEG-SPIONs were artificially designed to effectively operate at low magnetic field strengths (<100 mT) retaining approximately 60% of their saturation magnetization. Compared to other cells, stems cells were more sensitive to the interaction with actuated cubic ND-PEG-SPIONs, which clustered near the endoplasmic reticulum (ER). Luciferase, ELISA, and RT-qPCR analyses revealed a marked TRAIL downregulation (secretion levels were depleted down to 30%) when intracellular particles at 0.100 mg/mL Fe were actuated by magnetic fields (65 mT and 50 Hz for 30 min). Western blot studies indicated actuated, intracellular cubic ND-PEG-SPIONs can cause mild ER stress at short periods (up to 3 h) of postmagnetic field treatment thus leading to the unfolded protein response. We observed that the interaction of TRAIL polypeptides with ND-PEG can also contribute to this response. To prove the applicability of our approach, we used glioblastoma cells, which were exposed to TRAIL secreted from stem cells. We demonstrated that in the absence of MMA treatment, TRAIL essentially killed glioblastoma cells indiscriminately, but when treated with MMA, we were able to control the cell killing rate by adjusting the magnetic doses. This approach can expand the capabilities of stem cells to serve as smart vehicles for delivery of therapeutic proteins in a controlled manner without using interfering and expensive drugs, while retaining their potential to regenerate damaged tissue after treatment. This approach brings forth new alternatives to regulate protein expression noninvasively for cell therapy and other cancer therapies.

Magnetically-actuated hydrogel-based achiral planar microswimmers for SERS detection: In situ coprecipitation for continuous loading of iron oxide nanoparticles.

Ultraviolet lithography is a very promising technology used for the batch fabrication of biomedical microswimmers. However, creating microswimmers that can swim at low Reynolds number using biocompatible materials while retaining strong magnetic properties and excellent biomedical functionality is a great challenge. Most of the previously reported biomedical microswimmers possess either strong magnetic properties by using non-biocompatible nickel coating or good biocompatibility by using iron oxide particle-embedded hydrogel with weak magnetism, but not both. Alternatively, iron oxide nanoparticles can be coated on the surface of microswimmers to improve magnetic properties; however, this method limited the usability of the microswimmers' surfaces. To address these shortcomings, this work utilized an in situ synthesis technique to generate high magnetic content inside hydrogel-based achiral planar microswimmers while leaving their surfaces free to be functionalized for SERS detection. The hydrogel matrices of the magnetically actuated hydrogel-based microswimmers were first prepared by ultraviolet lithography. Then, the high concentration of iron oxide was achieved through multiple continuous in situ coprecipitation cycles. Finally, the SERS detection capability of magnetically actuated hydrogel-based microswimmers was enabled by uniformly growing silver nanoparticles on the surface of the microswimmers. In the motion control tests, the microswimmers showed a high swimming efficiency, high step-out frequency, and consistent synchronized motion. Furthermore, the magnetically actuated hydrogel-based microswimmers were able to improve the detection efficiency of analytes under magnetic guidance.

Biohybrid Magnetic Microrobots for Tumor Assassination and Active Tissue Regeneration.

Magnetic microrobots have attracted increasing research interest for diverse biomedical applications, such as targeted therapy and tissue regeneration. However, multifunctional microrobots with complex morphology at the microscale are urgently needed to be fabricated, actively controlled, and functionalized. In this study, the chrysanthemum pollen-derived biohybrid magnetic microrobots (CDBMRs) with spiny protrusion, hollow cavity, and porous surface structure were proposed for tumor assassination and active tissue regeneration. By exquisitely designing the sequential treatment process, CDBMRs were fabricated and the innate morphology of pollen templates was well preserved. Under magnetic field, CDBMR exhibited various individual and collective behaviors. CDBMRs were utilized for synergetic tumor treatment by the combination of magnetically controlled physical assassination and active drug delivery. Meanwhile, CDBMRs showed excellent ability for active cell delivery and tissue regeneration, which was further proved by enhanced osteogenesis ability. By making full use of the natural morphology of pollen grains, the biohybrid microrobots presented a promising strategy for effective tumor therapeutics and tissue regeneration.

Characterization of Tensile Stress-Dependent Directional Magnetic Incremental Permeability in Iron-Cobalt Magnetic Sheet: Towards Internal Stress Estimation through Non-Destructive Testing.

Iron-Cobalt ferromagnetic alloys are promoted for electrical energy conversion in aeronautic applications, but their high magnetostrictive coefficients may result in undesired behaviors. Internal stresses can be tuned to limit magnetostriction but must be adequately assessed in a non-destructive way during production. For this, directional magnetic incremental permeability is proposed in this work. For academic purposes, internal stresses have been replaced by homogenous external stress, which is easier to control using traction/compression testbench and results in similar effects. Tests have been limited to tensile stress stimuli, the worst-case scenario for magnetic stress observation on positive magnetostriction coefficient materials. Hysteresis cycles have been reconstructed from the incremental permeability measurement for stability and reproducibility of the measured quantities. The directionality of the sensor provides an additional degree of freedom in the magnetic response observation. The study reveals that an angle of π/2 between the DC (Hsurf DC) and the AC (Hsurf AC) magnetic excitations with a flux density Ba at HsurfDC = 10 kA·m-1 constitute the ideal experimental situation and the highest correlated parameter to a homogeneous imposed tensile stress. Magnetic incremental permeability is linked to the magnetic domain wall bulging magnetization mechanism; this study thus provides insights for understanding such a mechanism.

Functionalized Spiral-Rolling Millirobot for Upstream Swimming in Blood Vessel.

Untethered small robots with multiple functions show considerable potential as next-generation catheter-free systems for biomedical applications. However, owing to dynamic blood flow, even effective upstream swimming in blood vessels remains a challenge for the robot, let alone performing medical tasks. This paper presents an untethered millirobot with a streamlined shape that integrates the engine, delivery, and biopsy modules. Based on the proposed spiral-rolling strategy, this robot can move upstream at a record-breaking speed of ≈14 mm s-1 against a blood phantom flow of 136 mm s-1 . Moreover, benefiting from the bioinspired self-sealing orifice and easy-open auto-closed biopsy needle sheath, this robot facilitates several biomedical tasks in blood vessels, such as in vivo drug delivery, tissue and liquid biopsy, and cell transportation in rabbit arteries. This study will benefit the development of wireless millirobots for controllable, minimally invasive, highly integrated, and multifunctional endovascular interventions and will inspire new designs of miniature devices for biomedical applications.

Biomateriales compuestos para restauración ósea obtenidos mediante tecnologías basadas en el uso del campo electromagnético / Composite biomaterials for bone restoration obtained by technologies based on the use of the electromagnetic

Introducción: El panorama demográfico en el mundo está cambiando. La población mayor de 60 años es el segmento que está creciendo más rápidamente y en el que las enfermedades del tejido óseo se presentan con más frecuencia, lo que aumenta la demanda de materiales y tecnologías apropiadas para restaurar estos tejidos. Objetivo: Analizar la información que se ha generado sobre el desarrollo de biomateriales compuestos para la reparación ósea, con énfasis en la identificación de las tecnologías emergentes basadas en el uso del campo electromagnético, sus aplicaciones y potencialidades. Métodos: Se consultaron trabajos científicos publicados en libros, revistas, patentes y tesis. El 80 por ciento de la documentación seleccionada pertenece al periodo 2010-2019. Análisis e integración de la información: Los métodos identificados fueron clasificados en cinco grupos: electrodeposición química, ya sea por electrólisis, electroforesis o síntesis electroforética in situ; electroporación; electrohilado; control magnético distal y bioestimulación electromagnética de células y tejidos, directamente o por la introducción de dispositivos que convierten la energía electromagnética en energía mecánica. Conclusiones: Estos métodos permiten la conformación de matrices celulares y acelulares compuestas y, además, dispositivos bioestimuladores con control de los parámetros de construcción y acción, de tal manera, que se logran procesos con mayor grado de reproducibilidad y a la medida de los requerimientos específicos para cada paciente(AU)

Introduction: The global demographic panorama is changing. The population aged over 60 years is the fastest growing segment, as well as the one where bone tissue diseases are most common, increasing the demand of appropriate materials and technologies to restore those tissues. Objective: To analyze the information so far generated about the development of composite biomaterials for bone repair, with an emphasis on the identification of emerging technologies based on the use of the electromagnetic field, its applications and potential. Methods: An analysis was performed of scientific papers published in books, journals, patents and theses. Of the documentation selected, 80 percent was from the period 2010-2019. Data analysis and integration: The methods identified were classified into five groups: chemical electrodeposition, be it by in situ electrophoretic synthesis, electrolysis or electrophoresis; electroporation; electrospinning; distal magnetic control and electromagnetic biostimulation of cells and tissues, either directly or incorporating devices which convert electromagnetic energy into mechanical energy. Conclusions: These methods permit the conformation of composite cellular and acellular matrices as well as biostimulator devices controlling construction and action parameters in such a way that the processes obtained display greater reproducibility and are more in keeping with the specific requirements of each patient(AU)

Lipid Oxidation Induced by RF Waves and Mediated by Ferritin Iron Causes Activation of Ferritin-Tagged Ion Channels.

One approach to magnetogenetics uses radiofrequency (RF) waves to activate transient receptor potential channels (TRPV1 and TRPV4) that are coupled to cellular ferritins. The mechanisms underlying this effect are unclear and controversial. Theoretical calculations suggest that the heat produced by RF fields is likely orders of magnitude weaker than needed for channel activation. Using the FeRIC (Ferritin iron Redistribution to Ion Channels) system, we have uncovered a mechanism of activation of ferritin-tagged channels via a biochemical pathway initiated by RF disturbance of ferritin and mediated by ferritin-associated iron. We show that, in cells expressing TRPVFeRIC channels, RF increases the levels of the labile iron pool in a ferritin-dependent manner. Free iron participates in chemical reactions, producing reactive oxygen species and oxidized lipids that ultimately activate the TRPVFeRIC channels. This biochemical pathway predicts a similar RF-induced activation of other lipid-sensitive TRP channels and may guide future magnetogenetic designs.

MagnetoSuture: Tetherless Manipulation of Suture Needles.

This paper demonstrates the feasibility of ligation and tissue penetration for surgical suturing tasks using magnetically actuated suture needles. Manipulation of suture needles in minimally invasive surgery involves using articulated manual/robotic tools for needle steering and controlling needle-tissue or thread-tissue interactions. The large footprints of conventional articulated surgical tools significantly increase surgical invasiveness, potentially leading to longer recovery times, tissue damage, scarring, or associated infections. Aiming to address these issues, we investigate the feasibility of using magnetic fields to tetherlessly steer suture needles. The primary challenge of such a concept is to provide sufficient force for tissue penetration and ligation. In this work, we demonstrate proof-of-concept capabilities using the MagnetoSuture™ system, performing tissue penetration and ligation tasks using ex vivo tissues, customized NdFeB suture needles with attached threads, and remote-controlled magnetic fields. To evaluate the system performance, we conducted experiments demonstrating tetherless recreation of a purse string suture pattern, ligation of an excised segment of a rat intestine, and penetration of rat intestines.

µ-PIV Measurements of Flows Generated by Photolithography-Fabricated Achiral Microswimmers.

Robotic micro/nanoswimmers can potentially be used as tools for medical applications, such as drug delivery and noninvasive surgery. Recently, achiral microswimmers have gained significant attention because of their simple structures, which enables high-throughput fabrication and size scalability. Here, microparticle image velocimetry (µ-PIV) was used to study the hydrodynamics of achiral microswimmers near a boundary. The structures of these microswimmers resemble the letter L and were fabricated using photolithography and thin-film deposition. Through µ-PIV measurements, the velocity flow fields of the microswimmers rotating at different frequencies were observed. The results herein yield an understanding of the hydrodynamics of the L-shaped microswimmers, which will be useful in applications such as fluidic manipulation.

Cell Injection Millirobot Development and Evaluation in Microfluidic Chip.

We propose an innovative design of millirobot, which can achieve donor cell suction, delivery, and injection in a mammalian oocyte on a microfluidic chip. The millirobot body contains a hollow space that produces suction and ejection forces for the injection of cell nuclei using a nozzle at the tip of the robot. Specifically, a controller changes the hollow volume by balancing the magnetic and elastic forces of a membrane along with the motion of stages in the XY plane. A glass capillary attached to the tip of the robot contains a nozzle that is able to absorb and inject cell nuclei. The millirobot provides three degrees of freedom and generates micronewton forces. We demonstrate the effectiveness of the proposed millirobot through an experiment of the absorption and ejection of 20-µm particles from the nozzle using magnetic control in a microfluidic chip.

Steering and control of miniaturized untethered soft magnetic grippers with haptic assistance.

Untethered miniature robotics have recently shown promising results in several scenarios at the microscale, such as targeted drug delivery, microassembly, and biopsy procedures. However, the vast majority of these small-scale robots have very limited manipulation capabilities, and none of the steering systems currently available enable humans to intuitively and effectively control dexterous miniaturized robots in a remote environment. In this paper, we present an innovative micro teleoperation system with haptic assistance for the intuitive steering and control of miniaturized self-folding soft magnetic grippers in 2-D space. The soft grippers can be wirelessly positioned using weak magnetic fields and opened/closed by changing their temperature. An image-guided algorithm tracks the position of the controlled miniaturized gripper in the remote environment. A haptic interface provides the human operator with compelling haptic sensations about the interaction between the gripper and the environment, as well as enables the operator to intuitively control the target position and grasping configuration of the gripper. Finally, magnetic and thermal control systems regulate the position and grasping configuration of the gripper. The viability of the proposed approach is demonstrated through two experiments involving 26 human subjects. Providing haptic stimuli elicited statistically significant improvements in the performance of the considered navigation and micromanipulation tasks. Note to Practitioners-The ability to accurately and intuitively control the motion of miniaturized grippers in remote environments can open new exciting possibilities in the fields of minimally-invasive surgery, micromanipulation, biopsy, and drug delivery. This paper presents a micro teleoperation system with haptic assistance through which a clinician can easily control the motion and open/close capability of miniaturized wireless soft grippers. It introduces the underlying autonomous magnetic and thermal control systems, their interconnection with the master haptic interface, and an extensive evaluation in two real-world scenarios: following of a predetermined trajectory, and pick-and-place of a microscopic object.