Microrobotic Devices Integrated with Medical Imaging for in vivo Applications

Abstract

Microrobotic devices offer innovative solutions for minimally invasive diagnosis and treatment. Integrated with advanced imaging modalities, microrobotic devices enable precise navigation, real-time monitoring, and targeted interventions in complex anatomical environments. This perspective highlights the functional mechanisms of both tethered and untethered microrobots, exploring their applications across cardiovascular, nervous, digestive, sensory, and respiratory systems. The integration of microrobotics with artificial intelligence and advanced materials is expected to revolutionize personalized medicine and enable expanded treatment options for hard-to-reach regions in the human body.

Graphical abstract

Keywords

microrobotic devices / medical imaging / in vivo applications

Introduction

Microrobotics is an emerging field at the intersection of biomedical engineering and advanced imaging technologies, enabling precise, minimally invasive interventions within the human body. These miniature devices are uniquely designed to navigate complex and dynamic biological environments, unlocking transformative capabilities in drug delivery, diagnostics, and surgical procedures.

The integration of microrobots with real-time imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, has significantly expanded their potential for in vivo applications. These imaging systems enable accurate navigation, monitoring, and control of microrobots in real time, making it possible to perform sophisticated interventions with minimal disruption to surrounding tissues. Unlike traditional surgical tools, microrobots offer unparalleled controllability and the ability to localize treatment with high precision, reducing patient recovery time and the risk of systemic side effects. Microrobots leverage their small size, functional versatility, and advanced targeting capabilities to overcome critical challenges in accessing hard-to-reach regions of the human body.

This perspective examines the mechanisms of microrobots and their applications across various physiological systems. The following sections are organized to provide a comprehensive overview of the functional mechanisms of microrobots, categorized into tethered and untethered systems, as well as their applications in diverse medical contexts.

Functional mechanisms

Microrobots designed for in vivo applications are broadly classified into tethered systems, which rely on physical connections for power and control, and untethered systems, which are guided by external fields.

Tethered microrobotic systems

Tethered microrobotic systems, connected to external control units via catheters, ensure consistent power transmission, precise mechanical actuation, and integration of imaging. Recent advances in magnetically controlled medical robotics have enabled the development of magnetic continuum structures with variable stiffness properties[1].

Catheter-based systems are ideal for navigating complex anatomical pathways. Zhang et al. developed a soft bronchoscope with tendon-actuation and magnetic control to overcome limitations of traditional endoscopes[2], while Duan et al. designed a robotic bronchoscope with a three-degree-of-freedom end effector and electromagnetic tracking for precise pulmonary biopsies[3]. Thai et al. created F3DB, a soft robotic platform for in situ 3D bioprinting, capable of depositing biomaterials onto internal organs via a flexible robotic arm[4].

In interventional cardiology, electromagnetic guidewire systems represent a key advancement. Hwang et al. developed an electromagnetically controllable microrobotic system (ECMIS) that combines a magnetically steerable guidewire with a human-scale electromagnetic actuation system and biplane X-ray imaging for real-time visualization[5]. Mao et al. introduced a millimeter-scale magnetic steering continuum robot with “follow-the-leader” behavior for transluminal procedures, which uses phase transition components to achieve programmable shape control without relying on environmental interactions, enabling precise navigation through tortuous and fragile lumina with reduced tissue damage[6].

Untethered microrobotic systems

Untethered microrobotic systems are revolutionizing medicine with their superior maneuverability, reduced invasiveness, and ability to adapt to complex anatomical environments. These systems overcome many limitations of traditional approaches in drug delivery, tissue repair, diagnostics, and therapeutic interventions. Recent advances in bio-inspired microrobots have integrated multimodal actuation strategies to enhance environmental adaptability and enable autonomous responses to dynamic physiological barriers[7].

In drug delivery, untethered microrobots can cross barriers like the blood-brain barrier (BBB)[8,9], autonomously locate target cells[10,11], and release drugs via stimuli-responsive mechanisms, such as pH-sensitive systems for tumor microenvironments[12]. Their large surface area allows high drug-loading capacity[13], while functionalization with ligands or peptides ensures precise targeting. Magnetically actuated devices also enable localized drug deployment, such as for gastrointestinal lesions[14,15].

For tissue repair, microrobots deliver bioactive materials to sites inaccessible to traditional methods. Examples include 3D-printed helical transporters that maintain mesenchymal stem cell (MSC) viability[16] and magnetic scaffolds that enhance MSC differentiation and survival[17]. Advanced platforms like F3DB enable in situ 3D bioprinting, directly depositing biomaterials onto damaged internal tissues[4].

In diagnostics, microrobots enable real-time monitoring and precise detection. Fluorescent micromotors can detect biomarkers with high sensitivity[18], while robotic magnetic tweezers provide mechanical characterization[19]. Magnetically controlled nanorobots also improve imaging accuracy in techniques like gastrointestinal micro-computed tomography (micro-CT)[20].

Therapeutically, untethered microrobots can eliminate malignancies through hyperthermia[21], magneto-electric disruption[22], or mechanical forces[23]. For example, magnetic nanomotor swarms generate fluidic vortices to disrupt cancer cell membranes[24]. In vascular applications, spiral microrobots grind plaques without damaging vessel walls[25], while soft microrobots retrieve detached thrombi[26].

In vivo application

Recent advancements in microrobotic devices have enabled access to hard-to-reach areas within the human body[65], as shown in Figure 1. This section highlights their potential in emerging therapies and clinical applications, with Table 1 summarizing imaging and localization techniques across anatomical sites.

Diverse environmental factors highlight the complexity of analyzing and optimizing medical treatments across different regions of the human body. Microrobots face distinct challenges based on anatomical variations. For example, high flow rates in arteries require designs resistant to displacement, while lower flow rates in the gastrointestinal tract necessitate different propulsion strategies. Similarly, microrobots for narrow vessels, like cerebral or coronary arteries, must be highly miniaturized, whereas larger cavities, such as the stomach, allow greater flexibility in size. Imaging compatibility further influences microrobot design; for instance, MRI is suited for soft tissues, while endoscopy is preferred for the gastrointestinal tract. Navigation complexity also varies, with highly branched systems like the bronchial network requiring advanced steering and real-time decision-making, while simpler pathways, such as the urinary tract, permit more direct navigation. Table 2 summarizes organ spatial dimensions, imaging methods, fluid flow rates, and navigation complexity.

Circulatory System

The human circulatory system, including the heart, blood, and vessels, presents significant challenges for medical interventions due to complex flow dynamics and non-Newtonian blood viscosity. Cardiovascular diseases are a leading global cause of mortality[66], often resulting in vascular obstructions where traditional tools are invasive and less effective in small or intricate vessels. Microrobots provide minimally invasive and precise alternatives for navigating constrained environments.

Conventional thrombectomy methods, such as open surgery and mechanical extraction, pose risks of vascular trauma and have limited efficacy in small vessels. Microrobots offer innovative solutions, as illustrated in Figure 2. Xie et al. developed biomimetic magnetic microrobots (BMMs) capable of delivering tissue plasminogen activator (tPA) and dissolving clots through biochemical lysis and magnetic hyperthermia[67]. Khalil et al. introduced ultrasound-guided helical robots for clot removal via surface friction[27], while Wang et al. combined magnetic torque with real-time Doppler imaging, achieving significantly higher clot removal efficiency than conventional approaches[28].

Microrobots provide safer and more selective alternatives to traditional embolization techniques[68]. Biodegradable nanomaterials, such as poly (lactic-co-glycolic acid) (PLGA) microspheres[69], and hydrogel-magnetic nanoparticle systems with dual-modality imaging[31] enable targeted occlusion with reduced risks. Advances in microrobotics have also improved precision in cardiovascular surgeries. For example, Hwang et al. developed ECMIS, a system integrating magnetically steered guidewires with biplane imaging for precise vascular navigation[5].

Sensory system

The human sensory system includes organs such as the eyes, ears, nose, tongue, and skin. This section focuses on microrobotic applications in the eyes and ears.

Hearing loss, often caused by cisplatin-induced ototoxicity (CDDP)[70], is exacerbated by the difficulty of delivering drugs across barriers like the round window membrane (RWM) and blood-labyrinth barrier (BLB)[71,72]. Yi et al. developed a tube-type microrobot (TTMR) with magnetic and acoustic dual control to overcome these barriers[40]. The TTMR, constructed with chitosan, Fe₃O₄, and SiO₂, carried therapeutic agents and perfluorohexane (PFH). Magnetic navigation ensured precise targeting, while ultrasound-induced PFH vaporization propelled nanoparticles through barriers, enhancing drug penetration and mitigating CDDP-induced ototoxicity in vivo.

In the eye, delivering drugs to the posterior segment is hindered by the dense vitreous humor[73,74]. Wu et al. developed magnetically driven helical micropropellers with a slippery coating inspired by the Nepenthes pitcher plant to reduce adhesion in the vitreous, enabling retinal navigation within 30 minutes[35]. Further improvements came from Charreyron et al., who designed a flexible, magnetically controlled microcatheter that achieved a 93% success rate in navigating to retinal targets in an eye-phantom model[75].

Microrobotics have also improved precision in retinal surgeries, such as retinal-vein cannulation. Kummer et al. introduced the OctoMag system, a five-degree-of-freedom (5-DOF) magnetic control platform for microrobots, ensuring delicate procedures while limiting force to prevent retinal damage[36]. Liu et al. enhanced this system with optimized electromagnet parameters, an Active Disturbance Rejection Controller (ADRC), and a virtual boundary framework for greater safety and precision[38].

In the anterior segment, corneal endothelial transplantation requires extreme care to avoid damaging fragile tissue[76,77]. Yoo et al. addressed this by developing a magnetic field control system that uses magnetic filaments attached to corneal tissue[39].

Digestive system

The digestive system, comprising the gastrointestinal (GI) tract and accessory organs, presents significant challenges for medical intervention. Microrobotic systems have emerged as transformative tools for targeted delivery and therapy, particularly in navigating small, hard-to-reach channels where traditional endoscopy is limited[78–80].

Capsule endoscopy, a non-invasive alternative to rigid endoscopes, is widely used to diagnose conditions like Crohn’s disease and celiac disease[81]. These capsules, typically measuring 1.5 cm by 3 cm[41], can be enhanced with Artificial Intelligence (AI) for automated detection of tumors[82], polyps[83], and ulcers[84]. For instance, Anju et al.[42] developed a ResNet50-based Convolutional Neural Network (CNN)model with 99.16% accuracy on the Kvasir dataset. Advanced sensors further improve diagnostics: An et al.[46] introduced a magnetically actuated pH sensor capsule for diagnosing Helicobacter pylori, while Senthilnathan et al.[85] created magnetic microrobots with fluorescent memory for acidity monitoring.

In therapy, microrobots provide minimally invasive solutions, with representative designs in Figure 3. For drug delivery, Kim et al. developed a magnetic capsule with active locomotion and targeted release[48], while Xu et al. designed hydrogel capsules that disintegrate on demand[86]. Chen et al. proposed a multi-layer magnetic soft robot with tailored magnetic interactions to perform agile motions and multi-target adhesion in a stomach[87]. He et al. developed fluorescent soft robots that autonomously converge around metal clips to accurately locate tumors in the stomach during laparoscopic surgery[88]. Guo et al. presented a two-part robot for lesion localization and drug administration[89], and Hua et al. introduced a ferrofluid capsule robot with controlled rolling locomotion to reduce tissue damage[90]. Microrobots also enable precise tissue sampling and microbiota analysis. Leon-Rodriguez et al.[47] designed a capsule with foldable biopsy tools and electromagnetic actuation for targeted sampling. Nejati et al.[91] developed a pH-responsive smart capsule for microbiome analysis.

Musculoskeletal system

Osteochondral injuries, affecting both cartilage and subchondral bone, are a significant clinical challenge, particularly with aging populations and the increasing prevalence of osteoarthritis[92]. Traditional treatments fail to fully restore the complex osteochondral structure, while regenerative approaches like cell injections and scaffold transplants face issues of retention and invasiveness[93,94].

Microrobotic systems have emerged as innovative solutions for targeted cell delivery. Go et al. developed a microrobot system using PLGA scaffolds functionalized with magnetic microclusters to deliver human adipose-derived mesenchymal stem cells (hADMSCs) for knee cartilage regeneration[49]. Lee et al. enhanced this approach with magnetically actuated microscaffolds designed for simultaneous cartilage (MAM-CR) and subchondral bone regeneration (MAM-SBR)[50].

Huang et al. advanced the field by creating magnetized cartilage extracellular matrix (ECM)-derived scaffolds (M-CEDSs) from porcine ECM[51]. These microrobots efficiently delivered MSCs to injury sites under rotating magnetic fields, bridging the gap between decellularized scaffolds and magnetically actuated delivery.

Nervous system

The nervous system, comprising the central (CNS) and peripheral (PNS) systems, presents significant treatment challenges, particularly due to the blood-brain barrier (BBB). While stem cell therapies show promise for neurological disorders[95], traditional delivery methods face major limitations[96], As depicted in Figure 4.

Microrobots offer minimally invasive alternatives to bypass or cross the BBB. Jeon et al. developed “Cellbots”, magnetically powered stem cell-based microrobots that use superparamagnetic iron oxide nanoparticles (SPIONs) for precise delivery to the brain via the intranasal pathway[52]. For neural repair, Kim et al. introduced “Mag-Neurobot”, a magnetically actuated microrobot with microgrooved surfaces to bridge disconnected neural clusters and facilitate functional connections with hippocampal slices[53,54]. Chen et al. demonstrated piezoelectric helical microswimmers that generate localized electrical fields to induce neural cell differentiation[57], while Dong et al. designed biodegradable magnetoelectric microswimmers for magnetic actuation and electrostimulation[58].

For spinal cord injuries, Ye et al. developed biohybrid microrobots (“NPCbots”) integrating neural progenitor cells with magnetoelectric nanoparticles for regeneration. In drug delivery[59], Zhang et al. created “neutrobots,” combining chemotactic abilities of neutrophils with magnetic nanogels for targeted drug transport across the BBB[97]. Mair et al. introduced soft millirobots (“MANiACs”) capable of locomotion across brain and spinal cord tissues[55].

For glioblastoma therapy, Wu et al. presented a marsupial robotic system where magnetic continuum robots (“mother” robots) navigate to the tumor site and deploy “child” nanorobots for precise, on-demand drug delivery[56]. These innovations demonstrate the potential of microrobots to overcome neurological barriers and advance targeted therapies.

Urogenital system

The global decline in sperm quality has significantly impacted male fertility[98]. Engineered microrobots offer a promising solution for addressing motility deficiencies (asthenospermia) and low sperm count (oligospermia)[99–101]. Rajabasadi et al. developed multifunctional 4D-printed sperm-hybrid microcarriers using thermoresponsive hydrogels. These microcarriers can transport and release multiple motile sperm cells while promoting sperm capacitation with heparin and degrading the cumulus complex of oocyte using hyaluronidase[60].

In assisted reproductive technology, embryo transfer (ET) remains limited by the lack of precise control over the embryo’s placement within the uterine cavity. Koseki et al. addressed this challenge with a magnetically controlled microrobot system consisting of a microrobot, a catheter, and an external guiding magnet[61]. This system enables precise positioning of the embryo at the optimal implantation site, reducing the risk of ectopic pregnancy and improving implantation outcomes.

Respiratory system

Lung metastasis poses a major challenge in cancer treatment due to the poor targeting efficiency of systemic chemotherapy[102]. To address this, Zhang et al. developed a biohybrid microrobot, the algae-NP(DOX)-robot, which combines motile microalgae with red blood cell membrane-coated, doxorubicin-loaded nanoparticles[63]. In preclinical models of melanoma lung metastasis, this system demonstrated enhanced therapeutic efficacy. Similarly, microrobots have been explored for targeted antibiotic delivery in pulmonary bacterial infections. Zhang et al. modified Chlamydomonas reinhardtii microalgae with antibiotic-loaded nanoparticles, achieving active propulsion and deep lung tissue penetration in vivo[64].

For diagnosis, lung cancer remains the leading cause of cancer-related mortality[103]. Duan et al. developed a robotic bronchoscope with a compact, flexible end effector offering three degrees of freedom and electromagnetic tracking, enabling precise navigation and biopsy[3]. Similarly, Zhang et al. introduced a soft hybrid-actuated bronchoscopic robot featuring tendon-actuation and magnetic control, with an outer catheter and an inner magnetic working channel for improved maneuverability[2]. Kuan et al. designed a miniature serpentine robot for bronchoscopy, using backward path planning and real-time forward navigation to autonomously traverse the bronchial tree[62].

Future prospective

Biomedical microrobots navigating in vivo environments face heterogeneous and complex kinetic behaviors that often lack comprehensive characterization[104]. These challenges necessitate the integration of AI and Machine Learning (ML) into microrobotic control frameworks. For multi-agent coordination, Heuthe et al. proposed a Counterfactual Rewards (CR)-based control architecture[105], isolating individual agents’ contributions by computing a difference reward. This approach resolves the credit assignment problem in swarm robotics, enabling cooperative behaviors like precise cargo rotation under fluidic disturbances. In human-microrobot collaboration, Mao and Zhang combined Deep Reinforcement Learning (DRL) with Mixed Reality (MR) in a semi-autonomous control framework (DRL-SC)[106]. Using Proximal Policy Optimization (PPO) for autonomous pathfinding and a digital twin interface for manual intervention, their system improved navigation speed by 42% and reduced collisions in simulated microvascular environments.

Beyond control strategies, AI and deep learning are increasingly central to microrobotic design. Wang developed a unified topology optimization framework that co-designs structural topology, material magnetization, and external stimuli using the magneto-elastic Material Point Method (MPM)[107]. This method automates the creation of microrobot morphologies optimized for specific tasks, addressing challenges like large deformations and complex contact conditions.

The integration of microrobotic devices with advanced imaging technologies marks a significant advancement in in vivo medicine, offering precise drug delivery, minimally invasive surgeries, and real-time diagnostics. Their ability to navigate complex anatomical environments and operate at previously unreachable scales opens new possibilities for treating hard-to-access regions of the human body. However, challenges remain, including improving navigation in dynamic biological environments and ensuring clinical safety and efficacy. Advances in materials science, AI, and imaging technologies will further enhance microrobots’ adaptability and reliability, paving the way for their broader clinical adoption.

Looking ahead, the continued development of microrobotic systems is poised to revolutionize medical diagnostics and treatments, enabling more personalized and less invasive options for patients. As research progresses, microrobotics is expected to become a core component of routine medical practice, bringing us closer to a future where precision medicine is the standard of care.

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