Science Robotics: Tracking and navigation of a microswarm under laser speckle contrast imaging for targeted delivery

Micro/nanorobots harvest energy from internal or external environments to achieve active motion. This characteristic behavior of them permits a wide range of biomedical applications, especially in endovascular systems, such as thrombus removal, wound healing, and drug delivery, because of their tiny size and controllable locomotion. However, tracking these robotic swarms in real time has been a challenge, especially for imaging modalities that rely on prolonged exposure to ionizing radiation.

The paper reported the use of laser speckle contrast imaging (LSCI) (RFLSI III, RWD Life Sciences) for real-time tracking and navigation of magnetic microswarms in blood vessels, showcasing the potential of high-resolution micro/nanorobotic swarms imaging and navigation guided by LSCI in complex blood environments both in vivo and in vitro. These findings provide opportunities for improved targeted intravascular drug

First, the study introduces a novel control and tracking strategy using Laser Speckle Contrast Imaging (LSCI) for real-time tracking and navigation of a microswarm in different blood environments. It offers a noninvasive, full-field imaging approach with high temporal-spatial resolution. The study analyzes the interaction between the microswarm and the blood environment by quantitatively investigating the perfusion unit distribution. The LSCI technique allows for real-time monitoring and imaging of the microswarm and its surroundings, enabling simultaneous tracking and navigation in complex vascular systems.

Researchers used Fe₃O₄@ SiO₂ nanoparticles as building blocks to create magnetic microswarms. Microswarms were manipulated using a rotating magnetic field to exhibit swarm behaviors. In stagnant blood environments, the microswarm’s rotational motion effectively stirred the surrounding red blood cells (RBCs), which could be detected and imaged using LSCI. This allowed for a detailed analysis of the interactions between the swarm and its surrounding blood environment, as well as the evaluation of the hydrodynamic convection caused by the swarm. In dynamic blood environments, the microswarms were located by their contrast with the surrounding blood flow, enabling accurate tracking and navigation within the circulatory system.

To investigate the imaging and tracking of the microswarm in real tissue environments, the researchers used human placenta models. Applying LSCI technology, full-field images of real blood vessels with branches can be realized, thus the effective tracking of microswarms positions.

The researchers used a medical catheter to introduce nanoparticles into placental blood vessels, then formed a microswarm with a rotating magnetic field before testing the tracking and navigation capabilities of the swarm in these vessels under downstream and upstream flows. The findings proved that through real-time imaging feedback and effective control strategies, the microswarm remained stable under both antegrade and retrograde flows and displayed clear imaging signals. The researchers successfully tracked and navigated micro/nanorobotic swarms in placental vessels for five consecutive cycles, with a total navigation distance of approximately 400 millimeters.

These results demonstrated that with the guidance of LSCI, the control and tracking strategy proposed by the authors can achieve relatively long-distance and continuous navigation of micro/nanorobotic swarms in human placental blood vessels.

To further verify the imaging effect and navigation ability of microswarms in vivo, the researchers chose the rat femoral vein model and used LSCI to monitor the intravascular formation of swarms in real time. Results showcased that before injecting nanoparticles, there was no obvious imaging signal in the targeted vein. Yet after the injection, the particles gradually aggregated under the influence of a magnetic field and manifested the contour of microswarms in the blood vessels. Fully formed swarms exhibited higher contrast compared to nanoparticles in the aggregation process.

In summary, the LSCI-guided real-time tracking and high-precision navigation of magnetic microswarms is achievable in vascular environments both in vitro and in vivo. At the same time, this method can be applied to evaluate the interaction between microswarms and the blood environments quantitatively, and to efficiently deliver micro/nanorobots under higher-speed blood flow conditions (average flow 55 mm/s). This research offers a potent control strategy for micro/nanorobotic swarms to implement active intravascular targeted delivery, and contributes to the development and clinical application of microswarms-based therapeutic platforms.

Research highlights in methodology

This paper exemplifies the formation process of magnetic microswarms in the vascular system and the ability to track and navigate these swarms with high precision in complex blood environments in real time under LSCI guidance. It offers a noninvasive, full-field imaging approach with high temporal-spatial resolution. Researchers analyze the interaction between the microswarm and the blood environment by quantitatively investigating the perfusion unit distribution. This study has provided an effective tracking and navigation method of microswarms in a real-time manner, showcasing the great application potential of LSCI-guided microswarms for active intravascular targeted delivery.

Qinglong Wang et al., Sci Robot. 2024 Feb 21;9(87):eadh1978.

Free trial of RFLSI-ZW Laser Speckle Contrast Imaging System featured in the article.