Microrobots that can carry drugs and steer could provide targeted drug delivery

Microrobots formed in droplets could enable precision-targeted drug delivery, improving on I.V. drug delivery that sends only 0.7% of the drug to the target tissue, according to a recent study in Science Advances, conducted through simulations at the University of Michigan and experiments at the University of Oxford.

An experiment mimicking a treatment for inflammatory bowel disease, performed in a pig intestine and supported by simulations, demonstrated how the microrobots can be delivered by catheter and directed to a target site with a magnetic field. The microrobots are two-sided particles that are composed of a gel that can carry medicines and magnets that enable their control.

In the intestine experiment, when the gel dissolved, it delivered a dye that the team detected to ensure that the chemical cargo arrived at its target site. They also tested delayed release, with some gels dissolving over longer periods of time. After delivery, the magnetic particles were directed back to the catheter and retrieved.

If dispensed at multiple locations, this function could improve inflammatory bowel disease treatment; for instance, by delivering multiple drugs such as steroids, immunomodulators and regenerative agents to different inflammation sites along the intestine.

The team also tested a minimally invasive surgery use case with a model of a human knee. The microrobots were released at an easily accessible area, then maneuvered to a difficult-to-reach target site to dispense a dye before navigating back to the entry site for extraction.

“With this work, we’re moving closer towards very advanced therapeutic delivery. Our advanced fabrication techniques enable the creation of soft robotic systems with remarkable features and motion capabilities,” said Molly Stevens, the John Black Professor of Bionanoscience at the University of Oxford Institute of Biomedical Engineering and co-senior author of the study.

The particles that compose the microrobots are made by pushing a stream of gel containing magnetic particles through a narrow channel. A stream of oil enters the device and intersects the gel, pinching off evenly sized droplets. Magnetic gel particles sink to the bottom of the droplet and empty gel floats on the top.

The resulting devices, called permanent magnetic droplet-derived microrobots or PMDMs, measure about 0.2 millimeters, or the width of two human hairs.

“Traditional microrobot fabrication has very low throughput. Using microfluidics, we can generate hundreds of microrobots within minutes. It significantly increases efficiency and decreases fabrication cost,” said Yuanxiong Cao, a doctoral student in the Stevens Group at the University of Oxford and co-lead author of the study.

Simulations predicted and then fine-tuned how the microrobots move in response to specific magnetic field frequencies. Simulated obstacle courses served as a proving ground for steering the microrobots through complex environments.

The physical system uses an electromagnet controlled by commercial software, creating magnetic fields that form and move inchworm-like chains of microrobots. The chains move in three different ways, which the researchers refer to as walking, crawling or swinging. They can disassemble and reassemble on command, helping them traverse narrow passages or other obstructions.

“I was amazed to see how much control we have over the different particles, especially for the assembly and disassembly cycles, based on the magnetic field frequency,” said Philipp Schönhöfer, a co-lead author of the study and research investigator of chemical engineering at U-M in the group of Sharon Glotzer, the Anthony C. Lembke Department Chair of Chemical Engineering and co-senior author.

As a next step, the research team is designing new microrobots that can better navigate intricate environments. They will test different particles in emulsions to understand how they attract each other and study how larger particle swarms behave under varying magnetic fields.

“With our computational platform, we have now also developed a playground to explore an even wider design space, which has already triggered ideas for more complex microrobot architectures inspired by the PMDM concept,” Schönhöfer said.

Researchers from the Imperial College of London also contributed to the study.