Magnetically-driven robotic microscrew for the oviduct recanalization

Infertility is a disease of the reproductive system that affects 186 × 10⁶ people around the world.^1,2 Fallopian tube obstruction accounts for 11%–67% of female infertility cases.^3–5 The cause of the fallopian tube obstruction includes fibroids, endometriosis, and pelvic inflammatory disease. The current mainstream surgical approach to removing the blockage is represented by hysterosalpingography combined with conventional tubal catheters and guidewires.⁶ The minimum diameter of the fallopian tube is less than 1 mm.⁷ The traditional catheter can only reach the proximal fallopian tube, and the guidewire has poor steerability in the fallopian tube.^8,9 Therefore, it is challenging for this recanalization method to treat distal tubal obstruction. A medical device with a miniaturized feature and controlled steerability is needed to enter the distal fallopian tube and clear the blockage.

Miniaturized robots, relying on small dimensions and steerability, show great potential for minimally invasive surgery (e.g., cell manipulation,^10–12 laser-assisted treatment of vascular stenosis,¹³ active retentions,^14–16 drug delivery,^17,18 and clearing blockage vessels)^19,20 in narrow cavities (e.g., fallopian tubes and blood vessels). Currently, two main types of miniaturized robots are used to clear small luminal obstructions, including nanorobot clusters^21,22 and helical microrobots.^19,23,24 The nanorobot clusters take effect mainly by delivering drugs to the blocked area. Wan et al. proposed porous silica/platinum nanomotors to sequentially deliver drugs, including thrombolytic and anticoagulant drugs.²⁰ A near-infrared laser was used to generate the heat to propel the nanomotors and release the drug. Wang et al. proposed a magnetite nanoparticle microswarm to accelerate the tissue plasminogen activator (tPA) thrombolysis.²⁵ The magnetic nanomotor induced the 3-D fluid convection and the shear stress to increase contact between the drug and the blood clots under the external magnetic field. Wang et al. directly anchored the tPA on the surface of Fe₃O₄@mSiO₂ nanorobots to dissolve the thrombus through tumbling motion.²⁶ These nanomotors can be delivered and retrieved through a catheter. These robot clusters mentioned above target the blood clots. They are not suitable for the blocked fallopian tube since the drugs dissolving the blockage in the fallopian tube have not yet been developed.

The helical microrobots achieve recanalization by directly applying mechanical force to the blockage. Jeong et al. proposed a magnetically driven microrobot system that can remotely drive a bullet-shaped robot (2 mm diameter and 15 mm length) to easily penetrate an artificial thrombus in the arteries of a live pig.²³ The magnetic bullet-shaped robot without the helical structure was fabricated by conventional machining. Wang et al. reported a 3D printing strategy to fabricate a miniature helical robot (length 7.30 mm; diameter 2.15 mm). Two small magnets were inserted in the head to respond to the external magnetic torque and force. This robot has been applied for localizing thrombus and accelerating the thrombolysis rate. The small magnet restricts the miniaturization. Ma et al. fabricated a 7.5 mm long, 3 mm diameter spiral microrobot that can perform navigating and unclogging motions to clear the blood clots.²⁷ The high-resolution fabrication method successfully integrated a helical structure and two sharp tips on a slender cylinder to facilitate the motion and blockage penetration. Pozhitkova et al. outlined a soft helix robot (length 15 mm) based on a strip-shaped magnetic composition.²⁴ This helical robot can realize the recanalization by penetrating and extracting the blood clots through external rotating magnetic fields. However, the dimension of these robots designed for tubal evacuation is larger than 1 mm. They cannot be applied in the fallopian tube. Therefore, a miniaturized robot structure that can enter the depth of the fallopian tube is needed.

Here, we demonstrate a magnetically driven robotic microscrew to achieve fallopian tube recanalization. The magnetic robotic microscrew can move in the small-scale tube through a helical propulsion mode. The microscrew structure around the central cylindrical tube can generate the mechanical force to drill the mimic blockage under a rotating magnetic field. The propulsion speed and mechanical force can be modulated by changing the rotating frequency. Moreover, the vortex flow induced by the rotating robot can transport the destroyed fragments and enhance the drilling efficiency. As a result, we demonstrate the feasibility of the proposed microrobot as a concept for clearing the blockage in the fallopian tube, which proves the capability of recanalization in the small lumen.

We prototyped the screw-shaped microrobot consisting of a helical body, a cylindrical central tube, and a disk-shaped tail. The micro-scale screw-shaped structure with 800 μm length and 390 μm width is fabricated by high-resolution 3D microfabrication technology. Inspired by the shape characteristics of micro-organisms (e.g., spirochetes and spermatozoa), the helical structure around the cylindrical central tube is used as the main body of the robot for helical propulsion. The disk-shaped tail is added to make the microrobot tend to rotate around the central axis, and the cylinder central tube is used to enhance the structure stability during lithography. The magnetic microrobot is first constructed by 3D microfabrication technology on a glass substrate. Then an ultra-thin iron layer, deposited through magnetron sputtering, imparts magnetic properties, while a titanium layer, coated over the iron surface, enhances both stability and biocompatibility [Fig. 1(b)].

The propulsion capability of the robot is determined by the morphology. We designed four types of structures of the magnetic microrobots based on helical structure, including the screw structure, helix structure with a cylindrical cavity, helix structure with a needle-shaped tail, and twisted triangle structure, as shown in Fig. 2(a). The helical structure is designed to generate the propulsion force, and the needle structure and the triangular blade are designed to facilitate the penetration of the blockage.

To analyze the propulsion force of magnetic microrobots, a hydrodynamic simulation is carried out as shown in Fig. 2 and Movie S1. The velocity streamline has an obvious axial component along the microrobot, which indicates that the microrobots have an attraction effect on the fluid. A vortex flow field is created before the microrobot based on the attraction effect on the fluid. The driving force represents the mechanical mobility during the locomotion, and the friction represents the drilling capability during clearing the blockage. The driving force of the microrobot is proportional to the field rotating frequency before step-out [Fig. 2(b)]. When the robots contact the blockage, the driving force acts as the normal force to induce the friction force on the blockage. We assume the friction coefficient μ is set to be 0.2,²⁸ and the friction f is calculated by f = F_d × μ (F_d is the driving force, and μ is the friction coefficient). Therefore, we can modulate the driving force and friction force by controlling the frequency. Compared with the other three structures, the screw structure has an advantage in both driving force and friction. Therefore, we adopt the screw-shaped structure used to clear the blockage.

The magnetic microrobot is remotely driven by the external magnetic field (Fig. 3 and Movie S2). The robot is coated by magnetron sputtering with an extremely thin layer of iron. The ultrathin iron layer can be regarded as a superparamagnetic material. Therefore, the magnetization of the magnetic microrobots is zero without the external magnetic field. The microrobot can be magnetized under the external magnetic field. A glass channel with a diameter of 1.7 mm is used to mimic the fallopian tube. The magnetic field generator is used to generate the static field and the rotating magnetic field with the required strength, direction, and frequency. To test the magnetic responsibility, we first actuate the magnetic microrobot under the static field. When the microrobot is exposed to an external magnetic field, it naturally aligns its easy axis with the field direction, as illustrated in Fig. 3(a). This alignment allows for precise control of the microrobot’s orientation by manipulating the field. The interaction between the microrobot’s magnetic moment and the external field ensures stable alignment, enabling targeted navigation and actuation in biomedical applications. The microrobot follows the external magnetic field and rotates before step-out [Fig. 3(b)]. The robot’s motion speed is sequentially tested under the condition of the magnetic field rotational frequency of 1–11 Hz, and the results are shown in Fig. 3(b). We can see that the propulsion velocity is proportional to the rotating frequency of the magnetic field, which is consistent with the simulation results. Higher rotating frequency leads to higher velocity. When we need to penetrate the blockage, we adopt a high rotating frequency to increase the velocity and driving force. In addition, the fabricated microrobots were stored at room temperature. The magnetic microrobots exhibited stable magnetic responsiveness over the course of one week, confirming the durability of the iron nanolayer.

The recanalization effect of the magnetic microrobot on the blockage in the fallopian tube-mimicking glass tube is demonstrated by applying the external field (Fig. 4 and Movie S3). Most of the tubal obstructions are a mixture of cellular mucus composed of detached fragments of epithelial tissue from the inflamed lesions of the fallopian tubes, together with other cells and secretions. We use a cell cluster based on MDA-MB-231 cells (human breast cancer cells) to mimic obstruction. The tube is blocked in the center by this cell cluster [Fig. 4(a)]. The magnetic microrobots are pre-treated with trypsin to enhance the drilling capability when contacting the cells in the cluster.

When the microrobot spirals with its rotational axis aligned parallel to the channel wall, a large contact section forms between its sidewall and the channel, generating substantial frictional resistance. To minimize this resistance, it is essential to adjust the alignment of the magnetic field. By tilting the robot’s rotation axis 15° relative to the channel wall, the contact area decreases significantly, reducing friction. This adjustment allows the magnetic microscrew to achieve faster propulsion, enhancing efficiency and enabling smoother navigation through confined spaces. This approach ensures both reduced energy consumption and improved performance in complex environments, such as biological channels or microfluidic systems, where frictional forces can otherwise impede movement.

The microrobot rapidly approaches the blockage in the helical propulsion mode. When the microrobot touches the cells, the microrobot generates the mechanical forces to drill the cell cluster under the magnetic field (10 Hz, 15 mT). When the cell cluster is destroyed, the dispersed cells detached from the cluster are attracted and transported to the back of the microrobot through the vortex flow [Fig. 4(b)]. As shown in Fig. 4(c), the area of the cell cluster is gradually decreased within 18 s. After 18 s, the magnetic microrobot penetrates the blocked area and destroys the obstruction structure in a large area [Fig. 4(c)], verifying the feasibility of the microrobot to unblock the fallopian tube obstruction.

In summary, we developed a robotic microscrew capable of helical motion and blockage drilling. The microscale microrobot is engineered with complex structures (a helical structure, a cylindrical central tube, and a disk-shaped tail) based on high-resolution 3D microfabrication technology. The microscrew structure generates the propulsion force under the rotating magnetic field. We can modulate the speed in the fallopian tube-mimicking glass tube. The velocity reaches 1.5 mm/s. In the fallopian tube obstruction model, the magnetic microrobot can rapidly approach the mimic blockage based on the cell cluster. After contacting the blockage, the microrobot induces the friction force to destroy the cell cluster. The vortex field is an important aspect to enhance the drilling effect. The vortex field has been successfully created to transport cells to the back of microrobots. The area of the cell cluster is rapidly reduced within 18 s. Compared with other robots for obstruction recanalization, the present microrobot shows great potential in blockage recanalization in the small lumen with microscale dimension.

3D microfabrication of the robotic arrays was accomplished by microArch S240A (Boston Micro Fabrication). A 5 × 5 array was printed with photosensitive resin. Then the robot array was rinsed with isopropanol to clear up the remained resin. In this work, iron (Fe, 99.995%) and titanium (Ti, 99.995%) were coated through a magnetron sputterer (nanoPVD S10A, Moorfield Nanotechnology). The RF sputtering power of the iron target was set to 120 W. The sputtering gas flow was Argon with a flow rate of 50 sccm. The sputtering temperature was set to 180 °C. The sputtering time was set to 3 h, and the rotational speed of the sample stage was set to 5 rpm. The RF sputtering power of the titanium target was set to 105 W, and the sputtering gas flow was Argon with a flow rate of 40 sccm. The sputtering temperature was set to 180 °C, and the sputtering time was set to 30 min. The rotational speed of the sample stage was set to 5 rpm.

To accurately generate the magnetic field that drives the magnetic microrobot, a magnetic microrobot control platform was used in this work. The magnetic microrobot control platform consists of a microscope and a MagnebotiX MFG-100 magnetic field generator system (MagnebotiX Corporation) integrated on top of it. The MagnebotiX MFG-100 magnetic field generator system consisted of the MFG-100 magnetic field generator unit for generating the magnetic field, an ECB-820 electronic current supply for driving the coils, and MBX control software for calculating the current required to generate a user-specified magnetic field for the eight coils. The camera was used to monitor the magnetic micrometer robot's movement. The magnetic control platform was used to accurately control each parameter of the magnetic field.

MDA-MB-231 cells were cultured to simulate cellular blockage in the fallopian tube. Since the MDA-MB-231 cells have strong adhesion, the cells tend to adhere to each other and form cell clusters, which can simulate the blockage formed by cell accumulation. The cell culture medium used in the experiments consisted of 90% DMEM (ThermoFisher, model: 12491023), 10% fetal bovine serum (FBS) (ThermoFisher, model: 10100147C), and 1% penicillin-streptomycin solution (ThermoFisher, model: 15140148). Before the experiment, it is necessary to centrifuge the cells at 180 ×g for 3 min. Then the cells were stored in the centrifuge tube for 1–2 h to allow the cells to adhere to each other to form cell clusters. To enhance the disruptive effect on the cell-like clusters, the magnetic microrobots were treated with Trypsin (ThermoFisher, Model No. 25200056) for about 15 min.

The supplementary material is available. Movie S1: Hydrodynamic simulation of helical propulsion. Movie S2: Locomotion of the microrobots under the static and rotating fields. Movie S3: Obstruction recanalization based on the microrobot.

The work was supported by the National Natural Science Foundation of China Grant Nos. 52303167, 52203152, and 52305610, the Shenzhen Outstanding Talents Training Fund Grant Nos. RCBS20210706092255078 and RCBS20221008093222008, the Shenzhen Science and Technology Program Grant Nos. JCYJ20220818101409021 and JSGGKQTD20221101115654021, the Guangdong Basic and Applied Basic Research Foundation Grant No. 2024A1515010107, the Special Projects in Key Fields of Ordinary Colleges and Universities in Guangdong Province Grant No. 2022ZDZX3047, and the Obstetrics and Gynecology Open Fund of Peking University Third Hospital Grant No. BYSYSZKF2023013.

The authors have no conflicts to disclose.

X.L. and Y.L. contributed equally to this work.

Xiangchao Liu: Data curation (equal); Formal analysis (equal); Writing – original draft (equal). Yuan Liu: Conceptualization (equal); Formal analysis (equal); Writing – original draft (equal); Writing – review & editing (equal). Jing Huang: Formal analysis (equal). Xuhui Zhao: Data curation (equal); Formal analysis (equal). Jiangfan Yu: Resources (equal); Writing – review & editing (equal). Xiaopu Wang: Methodology (equal); Resources (equal); Writing – review & editing (equal). Haifeng Xu: Conceptualization (lead); Data curation (equal); Formal analysis (equal); Funding acquisition (equal); Project administration (lead); Resources (lead); Supervision (lead); Writing – original draft (equal); Writing – review & editing (equal).

The data that support the finding of this study are avaliable within the article and its supplementary material.