Citations

ABSTRACT Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the intestine’s integrated vascular, immune, and metabolic complexity. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37°C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

Rotating magnetic fields (RMFs) are widely used to actuate untethered microrobots, yet delivering clinically relevant RMFs at human scale remains challenging. Here, we create a quantitative framework for human‐scale RMF delivery using robot‐arm‐mounted permanent magnets. It links anatomical separation, surface‐clearance constraints, magnet geometry, rotational inertia, and robot‐arm limitations to define a feasible RMF operating envelope. Magnet geometry is most important when target separation is comparable to magnet size; in this regime, diametrically magnetized cylinders provide the most efficient field delivery at constant magnet volume. At larger separations, field delivery converges toward dipole‐like scaling and becomes primarily governed by total magnet volume. Across the dominant microrobot operating envelope (5–30 mT, 1–30 Hz), required magnet mass ranges from sub‐kilogram values for limb and intracranial targets to more than 30 kg for deep thoracic access. As magnet size increases, rotational inertia rapidly emerges as the dominant mechanical constraint, with limb and intracranial targets remaining feasible whereas some thoracic scenarios exceed practical mechanical limits. We demonstrate a representative actuator designed within the proposed framework tested on a human‐scale vascular phantom under flow. This work provides a foundation for codesigning translational microrobots and their magnetic drive platforms tailored for relevant anatomical targets.

ABSTRACT Atraumatic and localized drug delivery to the vascular endothelium remains a critical unmet need in interventional medicine, with major implications for arterial and venous disease management. Here, we present EndoBot, an untethered elastic millirobot designed to enable endothelial‐safe, soft‐contact operation, under physiologic blood flow. EndoBot is magnetically actuated and navigates along the vessel lumen through curved, non‐uniform geometries while maintaining ultra‐low radial contact pressures (<1 kPa), far below endothelial injury thresholds. We demonstrate stable locomotion, with intrinsically compliant mechanics within a defined safety envelope under arterial and venous hemodynamics in phantom vessels, ex vivo human umbilical veins, and an in vivo rat inferior vena cava, without detectable vessel damage. EndoBot is compatible with standard vascular sheaths for wireless deployment and retrieval and is controlled under clinical fluoroscopic guidance using a human‐scale magnetic manipulation platform. Blood compatibility testing confirms safety, with minimal hemolysis and no increased coagulation tendency during navigation. For localized therapy, EndoBot employs a gentle endoluminal painting strategy, transferring a washout‐resistant drug depot directly onto the vessel lumen. By combining atraumatic mobility, clinical deployability, and localized drug deposition, EndoBot establishes a translationally viable platform for developingmaintenance‐oriented endovascular therapies, supporting prevention of restonosis, thrombosis and inflammatory remodeling following intervention.

Abstract Magnetic Particle Imaging (MPI) is an advanced imaging modality that enables high temporal resolution functional imaging with zero tissue background signal. The adaptation of MPI scanners from small-animal research platforms to human-scale clinical applications introduces significant engineering challenges, particularly in generating high-gradient and temporally stable selection fields necessary for spatial encoding. Previous selection coil designs utilizing low-temperature superconductors (LTS), such as NbTi, have achieved the required gradient strengths but are dependent on liquid helium bath cooling. This reliance results in substantial operational costs, increased system complexity, and mechanical vibrations caused by cryogen boil-off and suspended cryostat structures, which may compromise image stability and signal integrity in MPI. High-temperature superconductors (HTS) have been investigated in recent years for high-gradient field generation in MPI applications due to their high current density and elevated operating temperatures. These studies indicate that HTS technology has the potential to address key limitations of LTS-based systems. However, the implementation of HTS magnets in human-scale MPI remains limited by unresolved challenges, including quench protection, mechanical robustness under large Lorentz forces, and the absence of integrated system-level design approaches tailored to MPI-specific requirements such as vibration suppression and gradient stability. This study introduces a next-generation HTS selection coil architecture specifically designed for human-scale MPI. The system utilizes REBCO tapes in a fully conduction-cooled, or 'dry,' configuration, thereby eliminating the need for liquid cryogens and providing a mechanically rigid structure that suppresses vibration sources. A no-insulation winding strategy with stainless steel reinforcement enables inherent quench self-protection and thermal stability. A comprehensive multi-physics design framework, integrating electromagnetic, thermal, and structural analyses, demonstrates a peak selection-field gradient of 5.58 T/m while maintaining both thermal and mechanical integrity. These results establish a robust and clinically viable pathway for HTS-based human-scale MPI systems.

Abstract Atraumatic and localized drug delivery to the vascular endothelium remains a critical unmet need in interventional medicine, with major implications for the management of arterial and venous diseases. Current approaches, such as drug-eluting stents and drug-coated balloons, combine mechanical revascularization with local drug release but frequently denude the endothelium and injure vessel walls, leading to restenosis, thrombosis, and chronic inflammatory repair cycles that severely limit long-term outcomes. Here, we present EndoBot, a soft, untethered millirobot designed for atraumatic navigation and targeted endovascular drug delivery during physiologic blood flow. EndoBot employs magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling to maintain low radial pressure (<1 kPa) and preserve endothelial integrity. Its feasibility is established in arterial and venous phantom models, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava, all under clinical fluoroscopic guidance using a human-scale magnetic manipulation system. Despite periodic vessel motion, compression, and geometric irregularities, EndoBot maintains stable, mechanically adaptive navigation without endothelial injury. Under real-time fluoroscopic imaging, we identify key challenges and showcase clinically feasible strategies for 3D localization and tracking, overcoming intrinsic depth limitations of 2D clinical imaging. The device can be deployed and retrieved through standard vascular sheaths and remains stable under supraphysiologic arterial and venous flow conditions (flow rate >100 mL min-1; flow velocity >155 cm s-1, shear stress >10 Pa). Blood-compatibility testing demonstrates no increase in coagulation tendency and minimal hemolysis (<0.01%) during magnetic actuation. For drug delivery, EndoBot employs a novel endoluminal painting-based technique that transfers a hydrophobic and flow-resistant coating directly onto the inner vessel surface. This method ensures uniform deposition of a biodegradable drug depot without generating fragments larger than typical capillary diameters (>10 mm). By enabling local, atraumatic drug delivery without compromising vessel wall integrity, EndoBot first time demonstrates a translationally viable platform for exploring effectiveness in preventive interventions in early-stage vascular disease and for adjunctive therapies in advanced disease stages.

ABSTRACT Atraumatic and precise drug delivery to arteries and veins remains an unmet need in interventional medicine, with significant implications for managing vascular diseases and long-term patient outcomes. Conventional endovascular methods, such as drug-coated balloons and drug-eluting stents, often damage vessel endothelium and compromise wall integrity, leading to reduced therapeutic efficacy and severe complications including restenosis and thrombosis. To address these limitations, we introduce EndoBot, an untethered soft millirobot designed for atraumatic vessel navigation and localized drug delivery under physiological blood flow. EndoBot achieves this through magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling, exerting low radial pressure (< 1 kPa) to preserve endothelial integrity. We validated its performance in phantom vessels, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava under fluoroscopic guidance using a human-scale magnetic manipulation platform. Despite dynamic vessel contractions and compressions along non-uniform cross-sections, mechanically adaptive locomotion strategy ensures safe navigation and protects the inner endothelial lining. EndoBot is deployable and retrievable via clinical vascular sheaths and remains stable even under supra-physiological blood flow conditions (> 155 cm/s). Extensive blood compatibility tests demonstrated minimal hemolysis (<0.01%), low platelet activation on the robot surface, and no increased coagulation tendency. For drug delivery, a hydrophobic transfer coating enables EndoBot to gently deposit a stable, flow-resistant drug layer onto the vessel wall without fragmentation. This novel platform enables safer and more effective targeted endovascular drug delivery, paving the way for transformative approaches to address early-stage vascular pathologies and deliver more effective preventive interventions.

This study examines the characteristics of various scanning trajectories or patterns under the influence of scanning parameters in order to develop a theory to define their corresponding image resolutions. The lack of an accurate estimation of pixel size for a specified set of scanning parameters and their connection is a key challenge with existing scanning methods. Thus, this research aimed to propose a novel approach to estimate the pixel size of different scanning techniques. The findings showed that there is a link between pixel size and a frequency ratio NP, which is the ratio of two waveform frequencies that regulates the density of the scanning pattern. A theory has been developed in this study to explain the relationship between scanning parameters and scanning density or pixel size, which was not previously considered. This unique theory permitted the a priori estimate of the image resolution using a particular set of scanning parameters, including the scan time, frequencies, frequency ratio, and their amplitudes. This paper presents a novel and systematic approach for estimating the pixel size of various scanning trajectories, offering the user additional flexibility in adjusting the scanning time or frequency to achieve the desired resolution. Our findings also reveal that in order to achieve a high-quality image with high signal-to-noise and low error, the scanning trajectory must be able to generate a fairly uniform or regular pattern with a small pixel size.

Targeted delivery of magnetic nanoparticles (MNPs) to an area of a blood vessel with fluidic flow is hampered by the lack of a suitable real‐time imaging modality for MNPs, the control system complexity, and low targeting performance. Herein, an offline programming guidance (OLPG) scheme for aggregated MNPs is proposed based on a real‐time aggregation volume estimator. The proposed aggregation volume estimator based on a magnetic drug‐targeting simulator reflects volume changes of aggregated MNPs; hence, it can model a magnetic force acting on aggregated MNPs in real time while enhancing targeting performance. The proposed guidance system is evaluated using a simulation testbed and in vitro model of the rat brain, which yields comparable results at different fluid viscosities, flow velocities, target areas, and flow types. The OLPG with the aggregation volume estimator improves targeting performance by 116%–409% compared with the default mode, and by 111%–180% compared to the performance without the aggregation volume estimator. Furthermore, a guidance margin predicts enhanced targeting performance (root‐mean‐square error < 5%) irrespective of the flow environment. The proposed guidance strategy has the potential to overcome the problems caused by the lack of an imaging modality, control‐system complexity, and low targeting performance.