Xing Liuxi, Cai Yulu, Zhang Yapei, Mozel Kevin, Tang Zhengxu, Tang Tengteng, Mottini Vittorio, Nigam Saumya, Smith Bryan R, Lee Ian Y, Nagaraja Tavarekere N, Wang Ping, Li Xiangjia, Gao Tong, Li Jinxing
Department of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Department of Aerospace and Mechanical Engineering, Arizona State University, Tempe, AZ, 85281, USA.
Adv Mater. 2025 Aug 11:e19708. doi: 10.1002/adma.202419708.
Microrobots hold immense potential in biomedical applications, including drug delivery, disease diagnostics, and minimally invasive surgeries. However, two key challenges hinder their clinical translation: achieving scalable and precision fabrication, and enabling non-invasive imaging and tracking within deep biological tissues. Magnetic particle imaging (MPI), a cutting-edge imaging modality, addresses these challenges by detecting the magnetization of nanoparticles and visualizing superparamagnetic nanoparticles (SPIONs) with sub-millimeter resolution, free from interference by biological tissues. This capability makes MPI an ideal tool for tracking magnetic microrobots in deep tissue environments. In this study, "TriMag" microrobots are introduced: 3D-printed microrobots with three integrated magnetic functionalities-magnetic actuation, magnetic particle imaging, and magnetic hyperthermia. The TriMag microrobots are fabricated using an innovative method that combines two-photon lithography for 3D printing biocompatible hydrogel structures with in situ chemical reactions to embed the hydrogel scaffold with FeO nanoparticles for good MPI contrast and CoFeO nanoparticles for efficient magnetothermal heating. This approach enables scalable, precise fabrication of helical magnetic hydrogel microrobots. The resulting TriMag microrobots, with the synergistic effects of FeO and CoFeO nanoparticles, demonstrate efficient magnetic actuation for controlled movement, precise imaging via MPI for imaging and tracking in biological fluid and organs, including porcine eye and mouse stomach, and magnetothermal heating for tumor ablation in a mouse model. By combining these capabilities, the fabrication and imaging approach provides a robust platform for non-invasive monitoring and manipulation of microrobots for transformative applications in medical treatment and biological research.
微型机器人在生物医学应用中具有巨大潜力,包括药物递送、疾病诊断和微创手术。然而,两个关键挑战阻碍了它们向临床转化:实现可扩展且精确的制造,以及在深层生物组织内实现非侵入性成像和跟踪。磁粒子成像(MPI)作为一种前沿的成像方式,通过检测纳米颗粒的磁化并以亚毫米分辨率可视化超顺磁性纳米颗粒(SPIONs)来应对这些挑战,不受生物组织干扰。这种能力使MPI成为在深层组织环境中跟踪磁性微型机器人的理想工具。在本研究中,引入了“TriMag”微型机器人:具有三种集成磁功能——磁驱动、磁粒子成像和磁热疗的3D打印微型机器人。TriMag微型机器人采用创新方法制造,该方法将用于3D打印生物相容性水凝胶结构的双光子光刻与原位化学反应相结合,将水凝胶支架嵌入FeO纳米颗粒以获得良好的MPI对比度,并嵌入CoFeO纳米颗粒以实现高效磁热加热。这种方法能够可扩展、精确地制造螺旋形磁性水凝胶微型机器人。由此产生的TriMag微型机器人,由于FeO和CoFeO纳米颗粒的协同作用,展示了用于受控运动的高效磁驱动、通过MPI在生物流体和器官(包括猪眼和小鼠胃)中进行成像和跟踪的精确成像,以及在小鼠模型中用于肿瘤消融的磁热疗。通过结合这些能力,制造和成像方法为微型机器人的非侵入性监测和操作提供了一个强大的平台,以用于医疗治疗和生物学研究中的变革性应用。