Label-free microcargo delivery and controllable release in complex fluidic environments based on autonomous magnetic microswarm | Microsystems & Nanoengineering

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Magnetic microswarms exhibit great potential for targeted delivery because of their excellent controllability and environmental adaptability. Enabling label-free cargo delivery and controllable release while endowing microswarms with resistance to environmental disturbances is…

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Magnetic microswarms exhibit great potential for targeted delivery because of their excellent controllability and environmental adaptability. Enabling label-free cargo delivery and controllable release while endowing microswarms with resistance to environmental disturbances is key to expanding their application scope. In this study, we present a label-free microcargo delivery strategy based on a magnetic microswarm actuated by a magnetic tweezers system. In this approach, high-frequency magnetic fields enable autonomous cargo capture, while low-frequency fields trigger controlled release, forming a simple yet effective frequency-switching mechanism. Owing to the high-intensity magnetic field produced by the magnetic tweezers system, the microswarm exhibits significantly improved anti-interference capability, ensuring stable transport even under dynamic flow conditions. Leveraging visual feedback, the microswarm autonomously captures and stably transports various microscale cargos, including polystyrene microspheres and cell spheroids up to 400 µm in diameter. In complex structures and flowing fluid environments, microswarms that carry cargo successfully resist fluid impacts and achieve autonomous navigation. Furthermore, the controllable release of nonmagnetic cargos is realized through a frequency-switching mechanism. When a microswarm carries multiple cargos, small cargos are usually discharged first, indicating the potential of this release mechanism to sequentially release multiple cargos. This strategy circumvents the risks associated with permanent magnetic labeling and enhances the microswarm’s anti-interference capability, providing essential technical support for the practical translation and clinical application of magnetic microrobots.

Microrobotics is a rapidly developing interdisciplinary field integrating materials science, robotics, and biomedical engineering. Owing to their small size and high maneuverability, microrobots can access narrow and complex anatomical regions that are often inaccessible using conventional minimally invasive devices. Consequently, microrobotics is spurring considerable interest in the precise delivery of microcargos, such as pharmaceuticals, stem cells, and diagnostic agents. Actuated by external fields, including magnetic, ultrasound, optical, or electric fields, microrobots can navigate precisely and deliver microcargos to designated sites, thereby significantly enhancing therapeutic precision and efficacy. Among the aforementioned external fields, magnetic fields provide precise, control and directional actuation with excellent biocompatibility and deep tissue penetration, making them particularly well suited for in vivo biomedical interventions. Magnetic microrobots that can successfully perform drug delivery and targeted cell transport have recently been demonstrated, highlighting their strong clinical potential.

However, individual magnetic microrobots are constrained by their limited payload capacity, and in vivo imaging technologies often possess insufficient resolution for real-time tracking at the microscale. Magnetic microswarms comprising multiple microrobots resolve this problem by enhancing the load capacity, improving imaging contrast, and displaying reconfigurability, allowing adaptation to complex and dynamic biological environments. Microswarms actuated by dynamic magnetic fields have been employed for nanoparticle delivery. Current swarm-based manipulation of nonmagnetic targets usually requires magnetic labeling or the fabrication of composite magnetic carriers, which may alter the biological functions of sensitive payloads such as cell spheroids, proteins, and drug molecules. Furthermore, residual magnetic components are difficult to retrieve after delivery, posing potential biotoxicity risks and limiting clinical safety. Therefore, a non-invasive strategy for manipulating nonmagnetic targets without magnetic modification is required. Several indirect approaches for controlling cargo have recently been explored. A paramagnetic multimodal microswarm has been utilized as an end effector to automatically manipulate micro-objects, which significantly enhances the degree of automation of the system. Furthermore, a novel planning strategy further improves the autonomy of magnetic microrobotic systems for micromanipulation tasks. Despite these successful demonstrations, the anti-interference capabilities of the delivery process require further improvement.

In this paper, we propose a label-free strategy for microcargo delivery using a microswarm composed of Fe3O4 nanoparticles. Under the control of a magnetic tweezers system, the microswarm enables capture, delivery, and release of microcargo. Integrated with a recognition algorithm, the microswarm achieves automated sequential capture based on the cargo size. Moreover, the cargo-carrying microswarm demonstrates autonomous navigation within complex structures. The high-intensity magnetic field generated by the magnetic tweezers system further enhances the microswarm’s anti-interference capability and cargo delivery performance. Under dynamic flow conditions, the microswarm successfully delivers cargo both downstream and upstream. Furthermore, we introduce a controllable release mechanism based on frequency switching. Tuning the rotation frequency dynamically adjusts the swarm morphology to independently release multiple cargos. During the release of cargos with different sizes, smaller targets are typically released first, indicating the potential application of this release mechanism for sequential multicargo release. This strategy avoids the safety hazards associated with permanent magnetic labeling and enhances the stability of the delivery process, exhibiting strong potential in intra-tissue targeted therapy.

In this study, a custom-built magnetic tweezers system was used to manipulate a magnetic microswarm. The magnetic tweezers system comprised an imaging device, a host computer, a base plate, permanent magnets, a rotating disk, and a translation stage, and its operating principle is illustrated in Fig. 1a. A controllable rotating magnetic field was generated by a pair of rectangular permanent magnets (10 mm × 10 mm × 10 mm) with a polar distance (d) of 15 mm. The spatial distribution of the magnetic field was simulated using COMSOL Multiphysics. The magnets increase the strength of the magnetic field, improving the anti-interference capabilities of the microswarm. Under the influence of the magnetic field, microparticles eventually assemble into a microswarm at point P, defined as the intersection of the rotating shaft (Rs) of the disk and the base plate. When the position of P changes, the microswarm moves with it. Thus, this characteristic was used to achieve the automated navigation of the microswarm.

The morphology of the magnetic microswarm is determined by the magnetic field height (h) from the magnets to the base plate, and the rotation frequency (f) of the magnets. In this study, Fe3O4 magnetic microparticles were used to form the magnetic microswarm. Figure 1b shows the morphological evolution of the microswarm under different magnetic field rotation frequencies (0.1–10 Hz) at a height of 20 mm and at different heights (15–35 mm) at a frequency of 6 Hz. The manipulation of microcargos can be achieved by modulating the morphology of the magnetic microswarm. When f < 1 Hz, the microswarm maintains a long chain-like configuration with large internal pores, which facilitates the release of the captured cargo. When f exceeds 1.5 Hz, the enhanced hydrodynamic force breaks the long chains, and the microswarms gradually reorganize into denser aggregates with clear outlines, thereby enabling the efficient capture of cargo. In addition to f, the parameter h significantly affects the microswarm morphology. As h increases, the microchains shorten, and the microswarm becomes more compact.

This structural evolution significantly affects the hydrodynamic behavior in its vicinity, thereby modulating the performance of the microswarm in target manipulation. A finite element model was established in this study to gain an in-depth insight into the intrinsic correlation between the microswarm structure and flow field characteristics. The microchain structures were simplified to rectangular geometries. The model simulated the flow field distribution around the microswarm at three representative frequencies (Fig. 1c). The rotational motion of the microswarm induced a vortex-like flow field centered on its core. As the microswarm approached the cargo, the resulting pressure gradient drew the cargo to the edge of the microswarm and guided its inward spiraling motion toward the center, thereby enabling efficient encapsulation. During directed locomotion, the encapsulated cargo was stably retained within the microswarm, facilitating synchronized transport.

The flow field distribution generated by the microswarm was closely correlated with the microchain scale. At a low frequency (f = 3 Hz), the microchains were excessively elongated, and the microswarm structure was loose, leading to reduced internal fluid velocity, weak pressure gradients, and ultimately low cargo capture efficiency. As the frequency increased (f = 6 Hz), the microchains reached a moderate length with reduced spacing, leading to a higher fluid velocity that enhanced the capability of the microswarm for cargo capture and retention. However, when the frequency was excessively high (f = 10 Hz), the microchains became too short and densely packed and formed a compact aggregate that restricted the internal fluid motion and reduced the cargo transport efficiency. Therefore, an optimal frequency threshold exists at which the microswarm transport performance is maximized, providing a theoretical foundation for subsequent precise manipulation.

Furthermore, we propose a frequency-switching strategy to release the captured cargo. When f was reduced below 1 Hz, the microchains rapidly restructured and elongated, forming a thick rod-shaped configuration. In this state, the microswarm exhibits a loose architecture with a significantly weakened flow-field capture force. We hypothesize that the rotational motion of this rod-shaped structure generates a thrust on the internal cargo, driving its migration toward the microswarm edge and causing it to gradually separate, thereby achieving controlled cargo release.

Figure 1d illustrates the complete workflow for delivering cargo using a microswarm. The magnetic microparticles injected into the working area are typically dispersed. Upon the application of a rotating magnetic field, they self-assemble into a microswarm. The visual feedback system tracks the real-time positions of the microswarm and cargo, enabling autonomous capture. After stable encapsulation, the microswarm carries the cargo for directional delivery. A frequency-switching mechanism is triggered upon reaching the release area. The subsequent restoration of the high-frequency magnetic field rapidly reconfigures the microswarm into a dense aggregate and withdraws it from the release area. This strategy enables label-free cargo delivery and controllable release. Moreover, the application of a high-strength magnetic field endows the microswarm with enhanced resistance to environmental disturbances, offering a practical technical pathway for minimally invasive delivery applications in complex biological environments.

The motion performance of the microswarm was evaluated through directional movement experiments. Figure 2a shows the microswarm moving along a triangular trajectory under the guidance of the magnetic tweezers. Figure 2b shows the superimposed trajectories of the actual path (red solid line) and desired path (blue dotted line) of the microswarm. Figure 2c shows the tracking errors between the actual and desired path. Despite the sharp turn of 60° during the experiment, the microswarm stably followed the desired path, with the maximum tracking error remaining within 0.5 mm. This excellent tracking capability demonstrates the potential of the system for microscale-targeted delivery.

The cargo-carrying performance was systematically evaluated for microswarms with varying doses of Fe3O4 particles (Fig. 2d). Experiments were conducted under a magnetic field with f = 6 Hz and h = 30 mm, using polystyrene microspheres (PSs) as cargos with diameters of 70–430 µm. As the particle dose increased, the maximum velocity (V max) of the cargo-carrying microswarm increased. However, the hydrodynamic drag force to be overcome by the microswarm increased significantly with the cargo diameter, which progressively reduced V max. When the cargo exceeded the structural bearing limit of the microswarm, it failed to follow the movement of the microswarm. Experiments demonstrated that microswarms formed from 2, 4, and 6 µL of magnetic particles stably transported PSs with diameters of 70–430 µm. Owing to its performance advantages, the microswarm assembled with 6 µL of particles was used in subsequent experiments.

In addition to the particle dose, both f and h influence the cargo-carrying capacity of the microswarm. The V max of microswarms transporting 250 and 300 µm PSs under different f and h is shown in Fig. 2e, f. At a fixed h of 30 mm, V max increases gradually with f, reaching a peak at 6 Hz. Further increase in f leads to denser microswarm structures, resulting in reduced transport efficiency. Similarly, when f is maintained at 6 Hz, increasing h initially promotes structural compaction and enhances V max, which peaks at 30 mm before decre

Source

• nature.com (2026-07-24)
• Original article: Label-free microcargo delivery and controllable release in complex fluidic environments based on autonomous magnetic microswarm | Microsystems & Nanoengineering