A Untethered Magnetic Micro-Robot for Local Therapeutic Delivery for Neurosurgical Oncology

Abstract

INTRODUCTION: Microrobots designed for biomedical applications have garnered significant research interest, offering advantages in drug delivery, microsurgery, and biopsies. Magnetic fields enabled by electromagnetic coils permit untethered nonlinear movement of these tiny robots within the brain on the surface, the cerebrospinal fluid, and parenchyma. Microdrillers (either individually or in swarms) are a promising tool for microsurgery, capable of drilling through viscoelastic media (brain tissue). However, challenges remain in scaling down the robot size and exploring diverse applications. METHODS: Parallelizable (batch) microfabrication involved 3D printing via two-photon lithography. The pH-sensitive hydrogel was synthesized through UV-initiated radical polymerization mixed with a tracer (fluorescein sodium salt). Imaging via photon-counting CT was performed for microbot tracking in preclinical models including hydrogel phantoms, large animal cadaveric fresh brain tissue, and human cadaveric tissue. RESULTS: Microbot speeds in various tissues were characterized with speeds up to 800 um/sec over magnetic field amplitudes of 5 to 55 mT while performing complex nonlinear trajectories via open-loop surgeon control via surgeon. Targeted hydrogel delivery of fluorescein label/nanoparticle drug over a pH range of 6.2 (tumor tissue) and 7.8 (normal tissue) over a time interval of 50 s is demonstrated as proof of concept with a rate of 2.4 times faster in acidic conditions. Lastly, we show state-of-the-art micromillmetric resolution for real time imaging via photon-counting spectral CT for implementation of closed loop control. CONCLUSIONS: A novel minimally invasive microrobotic platform technology capable of targeted local drug delivery in brain parenchyma is demonstrated.