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Do The Impossible

Building with Biology:
Tiny Bio-bots Powered by Living Cells

Miniature biological robots developed at Illinois are flexing their muscles. Engineers at the University of Illinois at Urbana-Champaign have demonstrated a class of walking “bio-bots” powered by muscle cells and controlled with electrical pulses, giving researchers unprecedented command over their function. These tiny cell-based soft robotic devices could have a transformative impact on our ability to design machines and systems that can sense and respond to a range of complex environmental signals.

"If we can rebuild existing systems with cells, we can also design new systems that harness the innate dynamic abilities of cells to self-organize and respond to environmental cues," explains graduate student Ritu Raman, co-first author of a 2014 PNAS publication introducing the current generation of 3D printed bio-bots. "This idea of forward-engineering integrated cellular systems with multiple functionalities is the founding principle of bio-bots."

Taking the Next Leap Forward

Ritu Raman (PhD, MechSE, '16) explains the impact of forward-engineering with "smart" biological materials.

“Biological actuation driven by cells is a fundamental need for any kind of biological machine you want to build,” said study leader Rashid Bashir, Abel Bliss Professor and head of bioengineering at Illinois. “We’re trying to integrate these principles of engineering with biology in a way that can be used to design and develop biological machines and systems for environmental and medical applications. Biology is tremendously powerful, and if we can somehow learn to harness its advantages for useful applications, it could bring about a lot of great things.”

Bashir’s group has been a pioneer in designing and building bio-bots, less than a centimeter in size, made of flexible 3-D printed hydrogels and living cells. Previously, the group demonstrated bio-bots that “walk” on their own, powered by beating heart cells from rats. However, heart cells constantly contract, denying researchers control over the bot’s motion. This makes it difficult to use heart cells to engineer a bio-bot that can be turned on and off, sped up or slowed down.

1st Gen. Bio-bot (2012)
Powered by beating heart cells

2nd Gen. Bio-bot (2014)
Powered by skeletal muscle cells

The current generation of bio-bots are powered by a strip of skeletal muscle cells that can be triggered by an electric pulse. This gives the researchers a simple way to control the bio-bots and opens the possibilities for other forward design principles, so engineers can customize bio-bots for specific applications.

“Skeletal muscles cells are very attractive because you can pace them using external signals,” Bashir said. “For example, you would use skeletal muscle when designing a device that you wanted to start functioning when it senses a chemical or when it received a certain signal. To us, it’s part of a design toolbox. We want to have different options that could be used by engineers to design these things.”

Walking Bio-bots

The design is inspired by the muscle-tendon-bone complex found in nature. There is a backbone of 3-D printed hydrogel, strong enough to give the bio-bot structure but flexible enough to bend like a joint. Two posts serve to anchor a strip of muscle to the backbone, like tendons attach muscle to bone, but the posts also act as feet for the bio-bot. A bot’s speed can be controlled by adjusting the frequency of the electric pulses. A higher frequency causes the muscle to contract faster, thus speeding up the bio-bot’s progress.

“It’s only natural that we would start from a bio-mimetic design principle, such as the native organization of the musculoskeletal system, as a jumping-off point,” said graduate student Caroline Cvetkovic, co-first author of the 2014 PNAS publication.

“This work represents an important first step in the development and control of biological machines that can be stimulated, trained, or programmed to do work. It’s exciting to think that this system could eventually evolve into a generation of biological machines that could aid in drug delivery, surgical robotics, ‘smart’ implants, or mobile environmental analyzers, among countless other applications.”

How Walking Biobots Work

Ritu Raman (PhD, MechSE, '16) explains the science behind walking bio-bots.

The researchers are currently working to gain even greater control over the bio-bots’ motion, for example, by integrating neurons so the bio-bots can be steered in different directions with light or chemical gradients. On the engineering side, they hope to design a hydrogel backbone that allows the bio-bot to move in different directions based on different signals. Thanks to 3-D printing, engineers can explore different shapes and designs quickly. Bashir and colleagues even plan to integrate a unit into undergraduate lab curriculum so that students can design different kinds of bio-bots.

“The idea is to be able to impart some sensing capabilities with specific neurons, that could sense a toxin or a specific biomarker in the blood, and then have cells that generate the antibodies against that, or some chemicals to neutralize that toxin,” Bashir explains. “These structures would have the capability to swim or walk. A colleague on campus, Professor Taher Saif, has been working on swimming devices that can propel through a fluid. So with the combination of these functionalities, you can imagine a device that can sense, move towards a gradient, and respond by delivering a chemical.”

CLINICAL APPLICATIONS OF BIO-BOTS

Prof. Rashid Bashir outlines short- and long-term implications
of bio-bot technology on the advancement of clinical care.

Taher Saif, the Gutgsell Professor of mechanical science and engineering at Illinois, has been working in collaboration with Bashir's group to lead development of a class of tiny bio-hybrid machines that swim like sperm. The swimming bio-bots are modeled after single-celled creatures with long tails called flagella. The researchers begin by creating the body of the bio-bot from a flexible polymer. Then they culture heart cells near the junction of the head and the tail. The cells self-align and synchronize to beat together, sending a wave down the tail that propels the bio-bot forward.

Swimming Biobots

"This self-organization is a remarkable emergent phenomenon," Saif said, "and how the cells communicate with each other on the flexible polymer tail is yet to be fully understood. But the cells must beat together, in the right direction, for the tail to move. It's the minimal amount of engineering—just a head and a wire. Then the cells come in, interact with the structure, and make it functional."

“The goal of ‘building with biology’ is not a new one—tissue engineering researchers have been working for many years to reverse engineer native tissue and organs, and this is very promising for medical applications,” said Raman, a partner in Bashir's lab. “But why stop there? We can go beyond this by using the dynamic abilities of cells to self-organize and respond to environmental cues to forward engineer non-natural biological machines and systems.

“The idea of doing forward engineering with these cell-based structures is very exciting,” Bashir said. “Being in control of the actuation is a big step forward toward that goal. The science of building with cells presents a variety of new opportunities.”

BUILDING WITH CELLULAR STRUCTURES

Prof. Rashid Bashir introduces the potential implications
of "building with biology" that extend beyond health and medicine.

The National Science Foundation supported this work through a Science and Technology Center (Emergent Behavior of Integrated Cellular Systems) grant, in collaboration with the Massachusetts Institute of Technology, the Georgia Institute of Technology and other partner institutions. Saif was also a co-author. Bashir also is affiliated with the Micro and Nanotechnology Laboratory, the departments of electrical and computer engineering and of mechanical science and engineering, Frederick Seitz Materials Research Laboratory and the Institute for Genomic Biology at Illinois.

Bio-Bot Research Group

“Looking at the big picture, our underlying goal for the center is to see if we can fabricate systems that don’t exist today, or if we can impart a function on systems that do exist—to create 'hyper-organs,'” Bashir imagines. “In the future, can we design with cells to make machines and systems that are living?”

When it comes to forward-engineering biology to improve the future of healthcare and medicine, it seems the impossible truly is within our reach.

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Contributors: Liz Ahlberg (eahlberg@illinois.edu) | Josh Nielsen (jniels@illinois.edu)