Tumbling microrobots tackle inflammatory bowel disease — and that’s only the beginning
It’s the stuff of science fiction — or it was until recently. Fantastic Voyage, a 1966 movie and related book, featured miniaturized submarine crew members traversing an injured scientist’s body to repair brain damage, and the 2014 animated film Big Hero 6 presented swarming healthcare microrobots.
For years, biomedical engineers have dreamed of bringing such technologies to life. For example, what if robots smaller than a grain of rice could move through the human body to deliver medications, and eventually also conduct diagnostic tests, clear blood clots and even perform surgeries — all with greater precision, fewer side effects and less trauma than conventional medicine allows?
These visions are becoming realities through research at Purdue’s College of Engineering in collaboration with the Indiana University School of Medicine (IUSM). Our ultimate goal is to design and implement an integrated microrobotics system for targeted delivery of custom therapeutics inside the human body for various diseases.
Unmet need — and opportunity
Currently, we’re focusing on colorectal disease — in particular, finding better ways to treat inflammatory bowel disease (IBD). Several factors point to an unmet clinical need, and opportunity, for more efficacious and less toxic drug treatments for this disease. IBD patients face significantly increased risk of colorectal cancer. However, today’s IBD pharmaceutical options are either topical and inconvenient or systemic with limited effectiveness and risk for serious adverse effects. A powerful solution for delivering medications locally and precisely would represent a major breakthrough.
Our team is creating magnetic microrobots and designing systems to help them provide targeted, localized drug delivery in the colon. Compared with conventional techniques, actively guided microrobots hold promise to be more effective, lower the risk of side effects and trauma, and offer higher drug retention rates. Benefiting from continuing design and fabrication advances, microrobots can be wirelessly controlled and steered to navigate complex topographies in the human body, such as those in the colon, to reach specific locations.
In 2020, using the colon of an anesthetized live mouse, we successfully demonstrated the first microscale robot tumbling through a biological system in vivo. Now, supported by a $1.11 million National Institutes of Health (NIH) grant, we are working to prove that a combined actuation/imaging system with high resolution, cross compatibility, a small footprint, and tissue penetration capabilities can be developed to actively guide minimally-invasive in vivo magnetic microrobots for the on-demand local delivery of compounds to treat IBD.
Engineering-medicine collaboration
Our research is part of the Purdue Institute for Cancer Research, and it aligns with Purdue Engineering Initiatives in Autonomous and Connected Systems and Engineering-Medicine.
The NIH-funded project has three aims, each led by a different Purdue team member. David Cappelleri is responsible for designing and building microrobots that can tumble (think back flips and side flips) through a live colon using external magnetic fields. The microrobots are made — inexpensively of polymer and metal, and nontoxic and biocompatible — at Purdue’s Birck Nanotechnology Center. Luis Solorio is leading efforts to design a drug loading and release system to enable microrobots to deliver a therapeutic payload. Craig Goergen is heading up designing a focused ultrasound heating system that the microrobots can use for active in vivo targeting and delivery of a therapeutic payload, as well as using traditional ultrasound for real time in vivo imaging of the microrobots.
Through the Engineering-Medicine initiative, Dr. Thomas F. Imperiale, at IUSM, is the clinical expert, advising on all aspects of the work. Trained in clinical epidemiology and gastroenterology, he directly treats many IBD patients in his clinical practice.
Challenges surmounted
We’ve overcome key challenges.
First, we achieved mobility and control of microrobots in various terrains and environments such as those in the body, including wet, sticky and non-smooth surfaces. We designed the microrobot to rotate with the rotating magnetic field, as cars and trucks traverse rough topography — with wheels that can roll over the magnetic field. The rectangular microrobot essentially functions as a rotating wheel driving over diverse terrains. We can speed it up or slow the magnetic field down by changing the frequency of the magnetic field. We also can modulate the direction of the field in the plane to steer the robot to different locations.
Next, we investigated how we could attach a drug payload to the robot for precise delivery to a targeted location. We developed a unique electrospraying technique to coat the robot with a mock drug payload and demonstrate delivery capabilities.
Of course, it’s necessary to know that the microrobot is at the targeted location. To visualize a microrobot, we developed an integrated actuation/imaging system consisting of a rotating permanent magnet and an ultrasound imaging device. The system was designed for small animal research so we could evaluate the entire system with in vivo studies. This is the first step toward translating our technology to humans for precision medicine applications.
What’s next?
Ability to directly access parts of the body that human medical providers can’t reach opens the possibility of more effective targeted treatment, ultimately throughout the body. Among important advantages, without the risk of systemic effects, drug concentrations can be more potent and diagnostic sampling can be more precise.
In the near future, we envision deploying teams and/or swarms of tumbling microrobots for diverse targeted drug delivery and diagnostic procedures — from chemotherapy treatments to biopsies to colonoscopies — in the gastrointestinal tract. Minimally invasive surgeries are a longer-term prospect.
New versions of microrobots can be created for additional areas of the body. For example, we’re developing a class of swimming microrobots that could work in arteries and other fluid-filled locations, clearing blood clots, delivering drugs and taking samples. Other classes of microrobots may arise to repair cells or wounds in vivo. Patients with cancers and neurological diseases are among those who could be helped.
We expect microrobots’ capabilities to expand as well. New opportunities are emerging with the advent of 3D and 4D printing. 3D printing of smart materials can give us 4D-printed microrobots, which can change their shape and/or material properties with different stimuli, enabling higher versatility and complexity in advanced applications.
Microrobots hold nearly unlimited potential for improving medical therapies — better treating and diagnosing disease, sparing patients side effects and trauma, and ultimately saving lives.
David J. Cappelleri, PhD
Assistant Vice President for Research Innovation, Office of Research
B.F.S. Schaefer Scholar and Professor, School of Mechanical Engineering
Professor, Weldon School of Biomedical Engineering (by Courtesy)
College of Engineering
Purdue University
Craig J. Goergen, PhD
Leslie A. Geddes Professor of Biomedical Engineering
Director of Clinical Programs, Weldon School of Biomedical Engineering
Faculty Council Co-Director, Purdue Engineering Initiative in Engineering-Medicine
College of Engineering, Purdue University
Adjunct Professor of Surgery
Indiana University School of Medicine
Luis Solorio, PhD
Associate Professor of Biomedical Engineering
College of Engineering, Purdue University
Thomas F. Imperiale, MD
Distinguished Professor, Indiana University
Lawrence Lumeng Professor of Gastroenterology and Hepatology
Professor of Medicine
Indiana University School of Medicine
Research Scientist, Roudebush VA Medical Center and Regenstrief Institute, Inc.
Adjunct Professor, School of Public Health
Medical Director, Margaret Mary Health
Related Links
Tackling inflammatory bowel disease with tumbling microrobots
All-terrain microrobot flips through a live colon
Swimming microrobots achieve record speeds, thanks to microscale 3D printing
Soft microrobots demonstrate potential for targeted drug delivery
‘World’s smallest drum’ expands horizons for microrobotics research
