This 3-millimeter microrobot is initially covered in wax as it travels inside the body. With a focused ultrasonic pulse, the wax melts and the liquid medication is delivered to a precise target. (Purdue University photo/Aaron Davis)

David Cappelleri, Professor of Mechanical Engineering and Biomedical Engineering (by courtesy), and Assistant Vice President for Research Innovation, has experimented with mobile microrobots for years. “We use an external magnetic field to tumble over complex topography, such as what you’d encounter inside a human body,” he said. “This enables us to make the robots very small, and control them very precisely.”

The robots need to be small enough to maneuver, but large enough to carry a significant drug payload — and precise enough to deliver it on command. To build such a tiny marvel, Cappelleri turned to the Nanoscribe 3D printer, which had already become famous for printing the world’s smallest drum for Guinness World Records. “This is the only machine on campus that can construct something that small and complex,” Cappelleri said.

Their team designed and 3D-printed a brick-shaped microrobot: 3 millimeters long, 1.5 millimeters wide, 1.5 millimeters high, and capable of carrying up to 20 microliters of medication. A rotating external magnet provided the energy for the microrobot to tumble in any direction, while an attached ultrasound probe enabled the operator to see inside and navigate precisely.

This 3-millimeter microrobot features a reservoir capable of holding up to 20 microliters of medication; a mechanical grid on top to lock the chambers with watertight wax; and neodymium magnets in the middle to provide for locomotion within the body. Purdue University researchers 3D-printed the microrobot in biocompatible resin using a Nanoscribe Photonic Professional GT2. (Purdue University photo/Aaron Davis)

So how do you deploy a drug payload on command, from a robot that tiny? “This turned out to be one of the biggest challenges of the project,” Cappelleri said. “How do we keep the medication safe as the robot travels, and then release it only when we’ve arrived at our destination?”

After considering mechanical approaches, the team came up with a simple solution: a food-safe wax that maintains a watertight seal at body temperature, but melts when its temperature is raised a few degrees. To actuate it, the team used an external focused ultrasonic pulse to melt the wax cap in about 60 seconds, thus releasing the medication from the robot’s reservoir.

Their research has been published in Advanced Robotics Research.

To conduct the in vivo tests, Cappelleri teamed up with Craig Goergen, Professor of Biomedical Engineering; and Luis Solorio, Associate Professor of Biomedical Engineering. In 2020 they successfully demonstrated the first tumbling microrobot through a biological system, and in 2021 simulated a targeted drug delivery. That led to a 3-year, $1.11 million project with the National Institutes of Health to conduct in vivo testing with real medications.

They decided to address colorectal disease, specifically inflammatory bowel disease (IBD). “There are several aspects that make IBD a perfect target for these robots,” said Goergen. “Most IBD therapies today have a broad effect on the entire gastrointestinal system, when it’s only a small section of the colon that might be inflamed. It’s a messy environment, and these robots have shown they can navigate the complex topography. When they’ve finished their work, they have a natural route to evacuate from the body. Precise interventions like this will reduce side effects for the patients.”

They conducted three distinct experiments to confirm their theories. In the first, they used a model colon to test the microrobot’s locomotion capabilities and stability of the wax cap at body temperatures.

In the next test, they filled the microrobot with a contrast agent, and used the magnetic control apparatus to navigate the robot to a specific area of the colon, after which they used the focused ultrasonic beam to melt the wax cap. The contrast agent only became visible after the actuation, meaning that there was no early leakage in the robot’s travels, and the targeted deployment was successful.

Finally, they used a cell assay to test efficacy of medication delivery. They filled the microrobot with doxorubicin (a medication proven to shrink cancerous cells) and navigated it to a cluster of harvested cancer cells. Just as before, the delivery was successful. 72 hours later, the cancer cells showed an expected therapeutic effect — meaning that the robots had successfully deployed a real-world targeted medication.

David Cappelleri creates microrobots, smaller than a grain of rice, that can tumble through a live colon using external magnetic fields. (Purdue University photo/Jared Pike)

“This is a huge success,” Cappelleri said. “We’ve successfully demonstrated system-level integration of all the parts necessary to deliver targeted drug payloads using microrobots.”

“It’s thrilling to think about the potential applications of this,” Goergen said. “We’ve started in the colon, but the possibilities are endless: ovarian cancer, brain cancer, organ dysfunction, blood vessels, the heart. Any part of the body that could benefit from targeted medications, we can potentially deliver those drugs using these microrobots.”

Provisional patents for this technology have been filed through Purdue Research Foundation’s Office of Technology Commercialization. If you’re interested in licensing this technology, please contact Patrick Finnerty at pwfinnerty@prf.org and reference PRF track code: PRF#70958.

This work was supported by NIH award 1U01TR004239-1 and the Purdue Institute for Cancer Research Pilot Grant 2023-24 Cycle 2 Award. All animals and methods used are in compliance with Purdue University’s Institutional Animal Care and Use Committee (IACUC) under protocol number 2002002016.

Source:
David Cappelleri, dcappell@purdue.edu
Craig Goergen, cgoergen@purdue.edu
Luis Solorio, lsolorio@purdue.edu

Writer:
Jared Pike, jaredpike@purdue.edu, 765-496-0374

Tumbling Magnetic Microrobots for Targeted In Vivo Drug Delivery in the GI Tract
Aaron C. Davis, Luis Carlos Sanjuan Acosta, Shubh P. Mehta, Baiyan Qi, Yang Yang, Luis Solorio, Craig J. Goergen, David J. Cappelleri
https://doi.org/10.1002/adrr.202500135
ABSTRACT: Achieving reliable, on-demand targeted drug release in dynamic environments such as the gastrointestinal tract remains a critical challenge. Here, we introduce a hollow two-photon polymerized microrobot whose ports are sealed by a mechanically interlocked heneicosane wax cap within a suspended microgrid, retaining seal integrity during locomotion in biologically relevant environments. In vitro, microrobots loaded with doxorubicin remained stable at body temperature (37°C) and exhibited complete, step-like discharge within 1 min once the bath temperature crossed the 40–42°C threshold. Guided by an integrated magnetic and robotic ultrasound system, microrobots were introduced rectally and navigated in vivo to the distal colon of anesthetized rats and visualized in real time. Focused ultrasound (FUS) heating to 42°C triggered on-demand release of an echogenic nanoparticle tracer, producing a distinct contrast plume. No release occurred before reaching the targeted release temperature, underscoring the design's high thermal specificity and leakage-free performance at body temperature. Therapeutic relevance was demonstrated in an inflammatory-bowel-disease cell model: doxorubicin-filled microrobots reduced MDA-MB-231 viability below the projected LC50 value after 72 h. Together, the heneicosane cap and the noninvasive FUS thermal trigger enable leakage-free storage, real-time navigation, and spatially confined drug release in vivo, advancing untethered microrobotic delivery toward clinically actionable, colon-targeted therapies.