MRI-powered Magnetic Miniature Capsule Robot with HIFU-controlled On-demand Drug Delivery

Authors: Mehmet Efe Tiryaki, Fatih Doğangün, Cem Balda Dayan, Paul Wrede, Metin Sitti · ICRA 2023

Licences

Open Access
Paper: CC BY 4.0

Everything below draws on the full paper under its CC BY 4.0 licence; its figure is credited to the authors.

TL;DR

An MRI scanner both images and pulls a 5 mm magnetic capsule; an air bubble plugs its drug hole until MRI-guided focused ultrasound removes it, with pressure setting the release rate.

Why it matters

The work combines MRI-powered magnetic navigation with MRI-compatible acoustic triggering in one system, so a single scanner can image, move the robot and initiate release. The authors report navigation in porcine intestine about two orders of magnitude faster than a passive capsule and release at several targets in one operation.

Problem

MRI scanners can image a magnetic miniature robot and pull it with their gradient coils, but such robots have had little function beyond navigation, because the scanner's magnetic and RF conditions rule out most remote triggers. Magnetic deformation-based release needs field control MRI coils cannot give, RF triggers interfere with imaging, and light cannot reach deep tissue; MRI-guided HIFU release had only been shown with passive targeting.

Proposed solution

A 5 mm 3D-printed polymer capsule with a 1.5 mm steel magnetic core and a single 500 µm hole traps an air bubble in the hole as a stopper. A modified gradient-echo sequence on a 7 T scanner alternates imaging and actuation gradients to steer the capsule, and an MRI-compatible HIFU transducer on a 2D piezo stage removes the bubble with an acoustic pulse, after which acoustic pressure sets the release rate.

Key insights

A hole in a near-hydrophobic printed shell traps an air bubble that seals the drug, and a HIFU pulse can remove it on demand.
Required acoustic pressure falls as hole diameter grows and rises with wall thickness, in a nearly linear relation to hole diameter.
Acoustic pressure controls the release rate, so the same capsule can release at several targets during one navigation run.
Higher pressures release faster but acoustic radiation forces push the capsule off the focus, so the operator must hold it in place with magnetic force.

Main results

Navigation in a 50 cm ex vivo porcine small intestine took 44.2 ± 10.1 s over 5 runs, an average of 1.13 cm/s; the abstract describes this as travel at up to 1.13 cm/s. The authors compare it with 0.025 cm/s reported for passive capsules.
The capsule's air bubble was removed at 1.25 MPa acoustic pressure.
Capsule emptying time: 158 ± 18 s at 1.4 MPa, 38 ± 5 s at 1.9 MPa and 20 ± 2 s at 2.4 MPa.
Drug was released at all four target points in a U-shaped agarose channel using MRI-powered positioning and 1.4 MPa pulses.
Capsules without a bubble leaked all their dye within 1 day at 4 °C, while capsules with a bubble showed no leakage after 4 days; the bubble survived a magnetic steerer at 500 rpm.
Contact angle of water on the printed shell material: 81.48 ± 1.71°.

Limitations

Only 2D control of the HIFU focal point and a fixed, limited focal distance because of the small-animal scanner's space.
Drug release cannot be seen in MR images because the magnetic core's artifact is as large as the camera's field of view, so release is controlled open-loop from estimated release rates.
Scaling the capsule down needs a physical model of bubble removal and release hydrodynamics, finer drug-loading needles, and a way to counter acoustic radiation forces.
Tests used non-biological fluids at room temperature in vitro; viscosity, pH, tissue acoustics and moving organs are expected to change release and have not been studied.
The multi-target release demonstration used a capsule without an air bubble and an MRI-conditioned camera for visual confirmation.

Field impact

Finalist for the ICRA 2023 Outstanding Healthcare and Medical Robotics Paper award, with 3 citations. No code, data or design files are released with the paper.

Abstract

Magnetic resonance imaging (MRI)-guided robotic systems offer great potential for new minimally invasive medical tools, including MRI-powered miniature robots. By re-purposing the imaging hardware of an MRI scanner, the magnetic miniature robot could be navigated into the remote part of the patient's body without needing tethered endoscopic tools. However, the state-of-art MRI-powered magnetic miniature robots have limited functionality besides navigation. Here, we propose an MRI-powered magnetic miniature capsule robot benefiting from acoustic streaming forces generated by MRI-guided high-intensity focus ultrasound (HIFU) for controlled drug release. Our design comprises a polymer capsule shell with a submillimeter-diameter drug-release hole that captures an air bubble functioning as a stopper. We use the HIFU pulse to initiate drug release by removing the air bubble once the capsule robot reaches the target location. By controlling acoustic pressure, we also regulate the drug release rate for multiple location targeting during navigation. We demonstrated that the proposed magnetic capsule robot could travel at high speed up to 1.13 cm/s in ex vivo porcine small intestine and release drug to multiple target sites in a single operation, using a combination of MRI-powered actuation and HIFU-controlled release. The proposed MRI-guided microrobotic drug release system will greatly impact minimally invasive medical procedures by allowing on-demand targeted drug delivery.

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