Magnetic soft robots are gaining significant attention in biomedical applications due to their inherent advantages: high shape reconfigurability, motion agility, and multi-functionality within physiological environments. Multi-layer designs further enhance loading capacity and functional complexity, crucial for targeted delivery. However, the complexities of interactions between soft layers and the assembly of robots with on-demand motion modes from multiple film-like layers remain significant challenges. This research addresses these limitations by developing a novel magnetic multi-layer soft robot capable of precise movements and controlled adhesion. The study explores the magnetic interactions between soft film-like layers with distinct in-plane structures, enabling the creation of a robot capable of performing agile motions and on-demand targeted adhesion. Each layer comprises a soft magnetic substrate and an adhesive film, whose mechanical properties and adhesion performance are rigorously characterized. The resulting robot can execute translational and tumbling locomotion modes, with the capability of on-demand separation, leaving one side layer adhered to the target tissue. The research aims to validate the feasibility of using this multi-layer robot for precise multi-target adhesion in a simulated and actual stomach environment. The potential of this technology lies in its application for minimally invasive procedures and targeted drug delivery, particularly in addressing challenges associated with gastric ulcers, which frequently occur in multiple locations within the gastrointestinal tract, hindering effective treatment with conventional oral medications. Current bioadhesive platforms, such as patches and hydrogels, aim to improve drug retention and tissue adhesion. However, the use of a magnetic multi-layer soft robot offers a superior, non-invasive method for precisely delivering these platforms to multiple ulcer sites.

Existing research highlights the potential of magnetic soft robots for biomedical applications, including minimally invasive surgeries and targeted drug delivery. Studies have demonstrated their ability to navigate complex terrains through various locomotion modes like rolling, crawling, and swimming, adapting to different environments by employing techniques such as surface microstructures (microspikes) and mucoadhesive films. Progress has been made in using these robots for tasks such as bioprinting in vivo, assisting urination, and cargo delivery in organs like the gastrointestinal tract and blood vessels. Examples include drug release using capsule-shaped robots and the delivery of therapeutic patches to ulcers. The challenge addressed in this paper is the lack of investigation into the interactions between layers within a multi-layer robot and the subsequent difficulty in realizing on-demand motion control and targeted adhesion. While prior work demonstrates single-layer robots for targeted delivery, the development of a multi-layer robot with the ability to selectively adhere and detach from different locations simultaneously remains largely unexplored.

This study employs a multi-pronged approach encompassing design, fabrication, characterization, simulation, and experimental validation. The design of the magnetic multi-layer soft robot involves three layers: a central layer and two side layers. Each layer integrates a soft magnetic substrate with its magnetization direction perpendicular to the surface, and a mucoadhesive film for adhesion to wet tissues. The substrates are engineered with distinct in-plane structures: side layers have a magnetic frame and non-magnetic base, while the central layer has a non-magnetic frame and magnetic base. This differential design enables both layer-to-layer attraction for robot integrity during locomotion and controlled separation at target sites. The adhesive film, composed of Carbopol (mucoadhesive material), Poloxamer, and HPMC, is systematically characterized to optimize its adhesion performance. The mechanical properties are determined using tensile and amplitude scanning tests to evaluate fracture stress, strain, storage modulus (G'), and loss modulus (G''). Adhesion performance is assessed using Lap-shear and T-peel tests to measure shear strength and interfacial toughness. The influence of Carbopol content, pressing time, and film thickness on adhesion is investigated. Hydration effects are studied via rheological tests, and a reciprocal stretching test evaluates retention time under simulated gastric conditions. Magnetic actuation is characterized through simulations and experiments to analyze translational and tumbling motions, determining the relationships between magnetic field strength, vertical distance, horizontal distance, step-out frequency, and robot speed. The on-demand separation process is simulated and experimentally validated by analyzing the effects of magnetic field strength and direction on stress distribution and layer-layer interactions. Ex-vivo experiments utilize porcine gastric tissue with artificial ulcers to demonstrate multi-target adhesion and separation, while in-vivo experiments in a porcine stomach employ ultrasound imaging for navigation and real-time monitoring. In-vitro biocompatibility tests using human gastric mucosal epithelial cells (GES-1) evaluate the biocompatibility of the adhesive film and soft magnetic substrate. Statistical analysis uses Student's t-test to compare data from different groups, with a significance level of p<0.05.

The research yielded several key findings. The optimized adhesive film, with a Carbopol:HPMC-Poloxamer ratio of 1:2, demonstrated a maximum shear strength of 7.10 ± 0.34 kPa and interfacial toughness of 29.44 ± 0.32 J/m². Adhesion strength increased with pressing time up to 1 minute and film thickness up to 70 µm, showing a positive correlation. The robot exhibited both translational and tumbling locomotion modes, controlled by manipulating external magnetic fields. Simulations and experiments showed the robot's ability to move at different speeds based on the magnetic field parameters. The on-demand separation strategy, achieved by flipping the robot using magnetic torque, was successfully validated both in simulation and experimentally. The stress analysis showed a significant increase in stress with increasing magnetic field strength and direction, facilitating the separation of adhered layers. Ex-vivo experiments on porcine gastric tissue demonstrated successful multi-target adhesion with three artificial ulcers. The robot successfully adhered to and covered each ulcer sequentially, separating layers as needed. The adhesion remained stable even after 12 hours of immersion in simulated gastric fluid. In-vivo experiments in a porcine stomach, guided by real-time ultrasound imaging, successfully demonstrated multi-target adhesion in the presence of gastric peristalsis and mucus secretion. The robot accurately navigated to and adhered to three ulcers, showcasing its effectiveness in a complex, dynamic environment. Biocompatibility tests revealed high cell viability (99.0% for the adhesive film and 97.5% for the magnetic substrate) indicating minimal cytotoxic effects.

The findings demonstrate the successful development and validation of a novel magnetic multi-layer soft robot for on-demand targeted adhesion. The tailored magnetic interactions and optimized adhesive film enabled agile locomotion and precise control over adhesion and separation. The successful multi-target adhesion in both ex-vivo and in-vivo experiments highlight the robot's potential for various biomedical applications, especially in the gastrointestinal tract. The ability to precisely target and adhere to multiple sites simultaneously, in the presence of mucus and peristaltic motion, addresses a critical need for improved treatment strategies for gastric ulcers and other conditions requiring targeted drug delivery or localized interventions. The high biocompatibility of the materials further enhances the clinical potential of this technology. These results represent a significant advancement in the field of magnetic soft robotics, paving the way for more sophisticated and effective minimally invasive medical interventions.

This research successfully designed, fabricated, and validated a magnetic multi-layer soft robot for on-demand targeted adhesion. The robot's unique layered structure, controlled magnetic interactions, and biocompatible materials allow for precise navigation, controlled adhesion, and on-demand detachment. Ex-vivo and in-vivo experiments demonstrated the robot's ability to achieve multi-target adhesion effectively. Future work could focus on integrating drug delivery capabilities, enhancing navigation techniques, and conducting more extensive in-vivo studies to translate this technology into clinical applications.

While the study demonstrated significant promise, some limitations exist. The in-vivo experiments were conducted on a limited number of porcine subjects, necessitating further studies to confirm the results' generalizability. The artificial ulcers created in the ex-vivo and in-vivo studies may not fully replicate the complexity of naturally occurring gastric ulcers. Long-term in-vivo studies are needed to evaluate the long-term biocompatibility and effectiveness of the robot. Further refinement of the ultrasound imaging and control algorithms could improve navigation precision and speed, particularly in complex environments.