—— 2024 ——


Tracking and Navigation of a Microswarm Under Laser Speckle Contrast Imaging for Targeted DeliveryScience Robotics. [Link]
Q. L. Wang^, Q. Q. Wang^, Z. P. Ning, K. F. Chan, J. L. Jiang, Y. Q. Wang, L. Su, S. Jiang, B. Wang, B. Y. M. Ip*, H. Ko, T. W. H. Leung, P. W. Y. Chiu, S. C. H. Yu, L. Zhang*

SciRob 2024 tPA
Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness. The change in dynamic convection induced by the microswarm can be quantitatively investigated by analyzing the perfusion unit (PU) distribution, offering an alternative approach to investigate the swarm behavior and its interaction with various blood environments. Both the microswarm and surrounding environment were monitored and imaged by LSCI in real time, and the images were further analyzed for simultaneous swarm tracking and navigation in the complex vascular system. Moreover, our strategy realized real-time tracking and delivery of a microswarm in vivo, showing promising potential for LSCI-guided active delivery of microswarm in the vascular system.

tPA-anchored Nanorobots For In Vivo Arterial Recanalization At Submillimeter-Scale SegmentsScience Advances. [Link]
B. Wang, Q. L. Wang, K. F. Chan, Z. P. Ning, Q. Q. Wang, F. T. Ji, H. J. Yang, S. Jiang, Z. F. Zhang, B. Y. M. Ip, H. Ko, J. P. W. Chung, M. Qiu, J. G. Han, P. W. Y. Chiu, J. J. Y. Sung, S. W. Du*, T. W. H. Leung*, S. C. H. Yu*, L. Zhang*

SciAdv 2024 tPA
Micro/nanorobots provide a promising approach for intravascular therapy with high precision. However, blood vessel is a highly complex system, and performing interventional therapy in those submillimeter segments remains challenging. While micro/nanorobots can enter submillimeter segments, they may still comprise nonbiodegradable parts, posing a considerable challenge for post-use removal. Here, we developed a retrievable magnetic colloidal microswarm, composed of tPA-anchored Fe3O4@mSiO2 nanorobots (tPA-nbots), to archive tPA-mediated thrombolysis under balloon catheter-assisted magnetic actuation with x-ray fluoroscopy imaging system (CMAFIS). By deploying tPA-nbot transcatheter to the vicinity of the thrombus, the tPA-nbot microswarms were magnetically actuated to the blood clot at the submillimeter vessels with high precision. After thrombolysis, the tPA-nbots can be retrieved via the CMAFIS, as demonstrated in ex vivo organ of human placenta and in vivo carotid artery of rabbit. The proposed colloidal microswarm provides a promising robotic tool with high spatial precision for enhanced thrombolysis with low side effects.

—— 2023 ——


Modularized microrobot with lock-and-detachable modules for targeted cell delivery in bile ductScience Advances. [Link]
L. Su, D. D. Jin*, Y. Q. Wang, Q. L. Wang, C. F. Pan, S. Jiang, H. J. Yang, Z. X. Yang, X. Wang, N. Xia, K. F. Chan*, P. W. Y. Chiu, J. J. Y. Sung, L. Zhang*

SciAdv 2023 mb for targeted cell delivery
The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design–based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.

Bioinspired self-assembled colloidal collectives drifting in three dimensions underwaterScience Advances. [Link]
M. M. Sun, S. H. Yang, J. L. Jiang, S. Jiang, M. Sitti*, and L. Zhang*

SciAdv 2023 SMM
Active matter systems feature a series of unique behaviors, including the emergence of collective self-assembly structures and collective migration. However, realizing collective entities formed by synthetic active matter in spaces without wall-bounded support makes it challenging to perform three-dimensional (3D) locomotion without dispersion. Inspired by the migration mechanism of plankton, we propose a bimodal actuation strategy in the artificial colloidal systems, i.e., combining magnetic and optical fields. The magnetic field triggers the self-assembly of magnetic colloidal particles to form a colloidal collective, maintaining numerous colloids as a dynamically stable entity. The optical field allows the colloidal collectives to generate convective flow through the photothermal effect, enabling them to use fluidic currents for 3D drifting. The collectives can perform 3D locomotion underwater, transit between the water-air interface, and have a controlled motion on the water surface. Our study provides insights into designing smart devices and materials, offering strategies for developing synthetic active matter capable of controllable collective movement in 3D space.

Swarming self-adhesive microgels enabled aneurysm on-demand embolization in physiological blood flow, Science Advances. [Link]
D. D. Jin, Q. L. Wang, K. F. Chan, N. Xia, H. J. Yang, Q. Q. Wang, S. C. H. Yu* and L. Zhang*

SciAdv 2023 Micogel
The recent rise of swarming microrobotics offers great promise in the revolution of minimally invasive embolization procedure for treating aneurysm. However, targeted embolization treatment of aneurysm using microrobots has significant challenges in the delivery capability and filling controllability. Here, we develop an interventional catheterization-integrated swarming microrobotic platform for aneurysm on-demand embolization in physiological blood flow. A pH-responsive self-healing hydrogel doped with magnetic and imaging agents is developed as the embolic microgels, which enables long-term self-adhesion under biological condition in a controllable manner. The embolization strategy is initiated by catheter-assisted deployment of swarming microgels, followed by the application of external magnetic field for targeted aggregation of microrobots into aneurysm sac under the real-time guidance of ultrasound and fluoroscopy imaging. Mild acidic stimulus is applied to trigger the welding of microgels with satisfactory bio-/hemocompatibility and physical stability and realize complete embolization. Our work presents a promising connection between the design and control of microrobotic swarms toward practical applications in dynamic environments.

Wirelessly powered deformable electronic stent for noninvasive electrical stimulation of lower esophageal sphincter, Science Advances. [Link]
C. Zhang^, C. F. Pan^, K. F. Chan*, J. Y. Gao, Z. X. Yang, K. K. C. Leung, D. D. Jin, Y. Q. Wang, N. Xia, Z. P. Ning, X. Wang, S. Jiang, Z. F. Zhang, Q. L. Wang, B. Hao, P. W. Y. Chiu* and L. Zhang*

SciAdv 2023 EStent
Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.

—— 2022 ——


Endoscope-assisted magnetic helical micromachine delivery for biofilm eradication in tympanostomy tubeScience Advances[Link]
Y. Dong^, L. Wang^, Z. F. Zhang, F. T. Ji, K. F. Chan, H. J. Yang, P. L. Chan, Z. X. Yang, Z. G. Chen, W. T. Chang*, Y. K. Chan*, J. Y. Sung, L. Zhang*

SciAdv 2022 T-tube
Occlusion of the T-tube (tympanostomy tube) is a common postoperative sequela related to bacterial biofilms. Confronting biofilm-related infections of T-tubes, maneuverable and effective treatments are still challenging presently. Here, we propose an endoscopy-assisted treatment procedure based on the wobbling Fe2O3 helical micromachine (HMM) with peroxidase-mimicking activity. Different from the ideal corkscrew motion, the Fe2O3 HMM applies a wobbling motion in the tube, inducing stronger mechanical force and fluid convections, which not only damages the biofilm occlusion into debris quickly but also enhances the catalytic generation and diffusion of reactive oxygen species (ROS) for killing bacteria cells. Moreover, the treatment procedure, which integrated the delivery, actuation, and retrieval of Fe2O3 HMM, was validated in the T-tube implanted in a human cadaver ex vivo. It enables the visual operation with ease and is gentle to the tympanic membrane and ossicles, which is promising in the clinical application.

Untethered small-scale magnetic soft robot with programmable magnetization and integrated multifunctional modulesScience Advances[Link]
Y. Dong, L. Wang, N. Xia, Z. X. Yang, C. Zhang, C. F. Pan, D. D. Jin, J. C. Zhang, C. Majidi*, L. Zhang*

SciAdv 2022 Origami
Intelligent magnetic soft robots capable of programmable structural changes and multifunctionality modalities depend on material architectures and methods for controlling magnetization profiles. While some efforts have been made, there are still key challenges in achieving programmable magnetization profile and creating heterogeneous architectures. Here, we directly embed programmed magnetization patterns (magnetization modules) into the adhesive sticker layers to construct soft robots with programmable magnetization profiles and geometries and then integrate spatially distributed functional modules. Functional modules including temperature and ultraviolet light sensing particles, pH sensing sheets, oil sensing foams, positioning electronic component, circuit foils, and therapy patch films are integrated into soft robots. These test beds are used to explore multimodal robot locomotion and various applications related to environmental sensing and detection, circuit repairing, and gastric ulcer coating, respectively. This proposed approach to engineering modular soft material systems has the potential to expand the functionality, versatility, and adaptability of soft robots.

Autonomous environment-adaptive microrobot swarm navigation enabled by deep learning-based real-time distribution planningNature Machine Intelligence. [Link]
L. D. Yang, J. L. Jiang, X. J. Gao, Q. L. Wang, Q. Dou, L. Zhang*
Nature MacInt 2022
Navigating a large swarm of micro-/nanorobots is critical for potential targeted delivery/therapy applications owing to the limited volume/function of a single microrobot, and microrobot swarms with distribution reconfigurability can adapt to environments during navigation. However, current microrobot swarms lack the intelligent behaviour to autonomously adjust their distribution and motion according to environmental change. Such autonomous navigation is challenging, and requires real-time appropriate decision-making capability of the swarm for unknown and unstructured environments. Here, to tackle this issue, we propose a framework that defines different autonomy levels for environment-adaptive microrobot swarm navigation and designs corresponding system components for each level. To realize high autonomy levels, real-time autonomous distribution planning is a key capability for the swarm, regarding which we show that deep learning is an enabling approach that allows the microrobot swarm to learn optimal distributions in extensive unstructured environmental morphologies. For real-world demonstration, we study the reconfigurable magnetic nanoparticle swarm and experimentally demonstrate autonomous swarm navigation for targeted delivery and cargo transport in environments with channels or obstacles. This work could introduce computational intelligence to micro-/nanorobot swarms, enabling them to autonomously make appropriate decisions during navigation in unstructured environments.

—— 2021 ——


Endoscopy-assisted magnetic navigation of biohybrid soft microrobots with rapid endoluminal delivery and imaging, Science Robotics[Link]
B. Wang^, K. F. Chan^, K. Yuan, Q. Q. Wang, X. F. Xia, L. D. Yang, H. Ko, Y. X. J. Wang, J. J. Y. Sung, P. W. Y. Chiu, L. Zhang*
SciRob 2021
High-precision delivery of microrobots at the whole-body scale is of considerable importance for efforts toward targeted therapeutic intervention. However, vision-based control of microrobots, to deep and narrow spaces inside the body, remains a challenge. Here, we report a soft and resilient magnetic cell microrobot with high biocompatibility that can interface with the human body and adapt to the complex surroundings while navigating inside the body. We achieve time-efficient delivery of soft microrobots using an integrated platform called endoscopy-assisted magnetic actuation with dual imaging system (EMADIS). EMADIS enables rapid deployment across multiple organ/tissue barriers at the whole-body scale and high-precision delivery of soft and biohybrid microrobots in real time to tiny regions with depth up to meter scale through natural orifice, which are commonly inaccessible and even invisible by conventional endoscope and medical robots. The precise delivery of magnetic stem cell spheroid microrobots (MSCSMs) by the EMADIS transesophageal into the bile duct with a total distance of about 100 centimeters can be completed within 8 minutes. The integration strategy offers a full clinical imaging technique–based therapeutic/intervention system, which broadens the accessibility of hitherto hard-to-access regions, by means of soft microrobots.

Ultrasound Doppler-guided real-time navigation of a magnetic microswarm for active endovascular deliveryScience Advances[Link]Q. Q. Wang, K. F. Chan, K. Schweizer, X. Z. Du, D. D. Jin, S. C. H. Yu, B. J. Nelson, L. Zhang*

SciAdv 2021
Swarming micro/nanorobots offer great promise in performing targeted delivery inside diverse hard-to-reach environments. However, swarm navigation in dynamic environments challenges delivery capability and real-time swarm localization. Here, we report a strategy to navigate a nanoparticle microswarm in real time under ultrasound Doppler imaging guidance for active endovascular delivery. A magnetic microswarm was formed and navigated near the boundary of vessels, where the reduced drag of blood flow and strong interactions between nanoparticles enable upstream and downstream navigation in flowing blood (mean velocity up to 40.8 mm/s). The microswarm-induced three-dimensional blood flow enables Doppler imaging from multiple viewing configurations and real-time tracking in different environments (i.e., stagnant, flowing blood, and pulsatile flow). We also demonstrate the ultrasound Doppler–guided swarm formation and navigation in the porcine coronary artery ex vivo. Our strategy presents a promising connection between swarm control and real-time imaging of microrobotic swarms for localized delivery in dynamic environments.

—— 2019 ——


Real-time tracking of fluorescent magnetic spore–based microrobots for remote detection of C. diff toxinsScience Advances[Link]Y. B. Zhang, L. Zhang, L. D. Yang, C. I. Vong, K. F. Chan, W. K. K. Wu, T. N. Y. Kwong, N. W. S. Lo, M. Ip, S. H. Wong, J. J. Y. Sung, P. W. Y. Chiu, L. Zhang*
A rapid, direct, and low-cost method for detecting bacterial toxins associated with common gastrointestinal diseases remains a great challenge despite numerous studies and clinical assays. Motion-based detection through tracking the emerging micro- and nanorobots has shown great potential in chemo- and biosensing due to accelerated “chemistry on the move”. Here, we described the use of fluorescent magnetic spore–based microrobots (FMSMs) as a highly efficient mobile sensing platform for the detection of toxins secreted by Clostridium difficile (C. diff) that were present in patients’ stool. These microrobots were synthesized rapidly and inexpensively by the direct deposition of magnetic nanoparticles and the subsequent encapsulation of sensing probes on the porous natural spores. Because of the cooperation effect of natural spore, magnetic Fe3O4 nanoparticles, and functionalized carbon nanodots, selective fluorescence detection of the prepared FMSMs is demonstrated in C. diff bacterial supernatant and even in actual clinical stool samples from infectious patients within tens of minutes, suggesting rapid response and good selectivity and sensitivity of FMSMs toward C. diff toxins.

Active generation and magnetic actuation of microrobotic swarms in bio-fluidsNature Communications[Link]
J. F. Yu^, D. D. Jin^, K. F. Chan, Q. Q. Wang, K. Yuan, L. Zhang*

Nature Comm 2019
In nature, various types of animals will form self-organised large-scale structures. Through designing wireless actuation methods, microrobots can emulate natural swarm behaviours, which have drawn extensive attention due to their great potential in biomedical applications. However, as the prerequisite for their in-vivo applications, whether microrobotic swarms can take effect in bio-fluids with complex components has yet to be fully investigated. In this work, we first categorise magnetic active swarms into three types, and individually investigate the generation and navigation behaviours of two types of the swarms in bio-fluids. The influences of viscosities, ionic strengths and mesh-like structures are studied. A strategy is then proposed to select the optimised swarms in different fluidic environments based on their physical properties, and the results are further validated in various bio-fluids. Moreover, we also realise the swarm generation and navigation in bovine eyeballs, which also validates the proposed prediction in the ex-vivo environment.

—— 2018 ——


Ultra-extensible ribbon-like magnetic microswarm, Nature Communications[Link]
J. F. Yu, B. Wang, X. Z. Du, Q. Q. Wang and L. Zhang*

Nature Comm 2018
Various types of structures self-organised by animals exist in nature, such as bird flocks and insect swarms, which stem from the local communications of vast numbers of limited individuals. Through the designing of algorithms and wireless communication, robotic systems can emulate some complex swarm structures in nature. However, creating a swarming robotic system at the microscale that embodies functional collective behaviours remains a challenge. Herein, we report a strategy to reconfigure paramagnetic nanoparticles into ribbon-like swarms using oscillating magnetic fields, and the mechanisms are analysed. By tuning the input fields, the microswarm can perform a reversible elongation with an extremely high aspect ratio, as well as splitting and merging. Moreover, we investigate the behaviours of the microswarm when it encounters solid boundaries, and demonstrate that under navigation, the colloidal microswarm passes through confined channel networks towards multiple targets with high access rates and high swarming pattern stability.

—— 2017 ——


Multifunctional biohybrid magnetite microrobots for imaging-guided therapy, Science Robotics. [Link]
X. Yan, Q. Zhou, M. Vincent, Y. Deng, J. F. Yu, J. Xu, T. Xu, T. Tang, L. Bian, Y. Wang, K. Kostarelos, L. Zhang*
SciAdv 2017
Magnetic microrobots and nanorobots can be remotely controlled to propel in complex biological fluids with high precision by using magnetic fields. Their potential for controlled navigation in hard-to-reach cavities of the human body makes them promising miniaturized robotic tools to diagnose and treat diseases in a minimally invasive manner. However, critical issues, such as motion tracking, biocompatibility, biodegradation, and diagnostic/therapeutic effects, need to be resolved to allow preclinical in vivo development and clinical trials. We report biohybrid magnetic robots endowed with multifunctional capabilities by integrating desired structural and functional attributes from a biological matrix and an engineered coating. Helical microswimmers were fabricated from Spirulina microalgae via a facile dip-coating process in magnetite (Fe3O4) suspensions, superparamagnetic, and equipped with robust navigation capability in various biofluids. The innate properties of the microalgae allowed in vivo fluorescence imaging and remote diagnostic sensing without the need for any surface modification. Furthermore, in vivo magnetic resonance imaging tracked a swarm of microswimmers inside rodent stomachs, a deep organ where fluorescence-based imaging ceased to work because of its penetration limitation. Meanwhile, the microswimmers were able to degrade and exhibited selective cytotoxicity to cancer cell lines, subject to the thickness of the Fe3O4 coating, which could be tailored via the dip-coating process. The biohybrid microrobots reported herein represent a microrobotic platform that could be further developed for in vivo imaging–guided therapy and a proof of concept for the engineering of multifunctional microrobotic and nanorobotic devices.