News

"Mapping The Body” in Newsweek

Published: October 1, 2014

“A new look at live cells in 3D”

Published: October 1, 2014

EBICS @ MIT Co-Hosts Career Development Panel

Published: July 27, 2014

EBICS @ MIT cohosted a Career Development Panel "On the Bridge Between Academia and Indutry" in partnership with MIT's Biological Enigineering department, the NIH Center for Integrated Synthetic Biology, and the MIT Postdoc Association. The panel was a huge success with record attendance.

Three EBICS Graduate Students Win Design Principles Prizes

Published: July 8, 2014

During a recent competition focused on soliciting ideas for EBICS Design Principles, thre EBICS graduate students took home top prizes. Raymond Swetenburg (UGA) won first place. Meghan Ferrall (GATech) and Jessica Mustard (Tufts) tied for second place prize. Entries were collected via an email list and judged by EBICS Advisory Committee members during the EBICS Retreat at University of Illinois, Urbana-Champaign. All submitted design principles from faculty and students will soon be become part of a searchable knowledge base on the EBICS website.

 

Congratulations again to all of winners!

Georgia Tech News Center: My summer in Africa with Manu Platt

Published: September 24, 2013

Dr. Manu Platt, Assistant Professor in the Wallace H. Coulter Dept. of Biomedical Engineering and EBICS Diversity Director, narrates a personal slideshow from his Summer research trip to South Africa and Ethiopia. His research focuses on how cells sense, respond, and remodel their immediate mechanical and biochemical environments for repair and regeneration in health and disease. Manu's group applies their expertise to further EBICS microvascular networks and computational modeling efforts. 

Watching tumors burst through a blood vessel

Published: September 19, 2013

Doug White wins Medtronic Excellence in Modeling Award

Published: September 3, 2013

Congratulations to Doug White from the McDevitt and Kemp labs at Georgia Tech on winning the Medtronic Excellence in Modeling Award to be presented in September at BMES.

Biobots research profiled in New York Times

Published: August 20, 2013

Rashid Bashir brings engineering to life

Published: June 24, 2013

AAAS Fellow Rashid Bashir explores and expands the crossroads of engineering and medicine. "I think bioengineers are always trying to understand and mimic biology," says Bashir. And maybe even go nature one better.

Hannah Merrick receives MIT's Infinite Mile Award, shown here with School of Engineering Assistant Dean Donna Savicki (left) and Dean Ian Waitz (right).

Hannah Merrick receives Infinite Mile Award from MIT's School of Engineering

Published: May 22, 2013

[Text delivered at Infinite Mile Ceremony, May 22, 2013.]

I am pleased to present Hannah Merrick with an Infinite Mile Award for Excellence. Hannah began as an Administrative Assistant to the center for Emergent Behaviors of Integrated Cellular Systems (EBICS) in the Department of Biological Engineering in May of 2011 and she quickly became a key member of the organization, easily fulfilling all position requirements and beyond.

EBICS is a large center, including about 130 faculty, postdocs and students across 11 institutions with a small administrative staff. Hannah assists with virtually every aspect of the Center from events planning and scheduling to record keeping, accounts reconciliation, and developing budgets; from designing flyers and announcements to analyzing data and generating charts and tables; from researching project management software to navigating the National Science Foundation (NSF) bureaucracy. 

Faculty say Hannah is “not satisfied with simply running an efficient, well-organized operation…[her] willingness to take on responsibilities outside of her defined job description and her willingness to learn new skills to help the Center distinguishes her as an employee who consistently goes beyond expectations.” One example of this was when the Center did not have the funds to hire a full-time web developer; Hannah took matters into her own hands.  “Through online tutorials and readings she learned to use the back end of our web platform and was able to build the necessary portions of the site herself, allowing the Center to meet [their] critical reporting deadline[s]”.

As if that’s not enough, Hannah gracefully juggled all administrative responsibilities for the Center during a month-long gap while the Center was between managers. During the transition between managers was the annual NSF Site Visit review of the Center where she organized all efforts for this high-stakes, three-day, 50-person event involving multiple NSF offices and nearly all Center partner organizations. While this job is normally handled by two staff members, Hannah took on the 13 presentations, a poster session, a videoconference meeting with senior university administrators across three time zones, and multiple small group events held simultaneously at separate locations.  In addition, she coordinated with multiple hotels, oversaw catering to accommodate various dietary restrictions, managed internet conductivity and other IT issues during this critical site visit with grace and ease. 

We are told that Hannah’s initiative is impressive as evidenced by the considerable time and effort she put into understanding the research projects.  Consequently even though she had limited training in science, she was able to assist in scientific writing and editing while managing the research communication forum.  Faculty call Hannah’s achievement this year “nothing short of remarkable”.

Hannah, I’m thrilled to present you with an Infinite Mile Award for excellence for your extraordinary skills and willingness to go above and beyond.

Stem Cell Report 2013

Report released, "Global Assessment of Stem Cell Engineering"

Published: February 28, 2013

The study, conducted by the World Technology Evaluation Center (WTEC), aims to assess the current status and the trends of stem cell engineering, and compare U.S. research and development programs with those abroad.

UGA biology graduate student Raymond Swetenberg (in photo) is doing research on stem cells for Aruna Biomedical.

Innovation on the Rise in Georgia

Published: December 3, 2012

Tue., December 4, 2012 4:00pm (EST) | By Jeanne Bonner

 

ATLANTA  —   

Georgia lost more than 300,000 jobs during the Great Recession. And many companies have gone belly up. But, that doesn’t mean innovation has dried up or cutting edge companies have stopped forming in Georgia. UGA biology graduate student Raymond Swetenberg (in photo) is doing research on stem cells for Aruna Biomedical.

Georgia lost more than 300,000 jobs during the Great Recession. And many companies have gone belly up. But, that doesn’t mean innovation has dried up or cutting edge companies have stopped forming in Georgia.

It’s a sunny fall morning at the University of Georgia in Athens and biology graduate student Raymond Swetenberg is hunched over his workspace. 

But he’s not in the library or at a campus job. He’s deep in a lab filled with industrial refrigerators and bio equipment, doing research for Aruna Biomedical. It’s a company founded by his professor, Steven Stice.

Wearing latex gloves and peering through a microscope, Swetenberg is examining stem cells submerged in formaldehyde.

“I’m doing what we call fixing cells in formaldehyde,” he said. “Kind of like you think of old organs in old scientists’ labs that are stuck in formaldehyde. It’s kind of like putting the cells in suspended animation. Then we can examine them a little better.”

Aruna develops stem cells that companies use to find cures for diseases. Pfizer, the pharmaceutical giant, for example, is using them for a treatment for Alzheimers’.

Stice says that means Aruna is converting research conducted at UGA into a tangible product to sell. 

“That’s why I came to the University of Georgia 14 years ago….is to be able to move technology from my academic lab and commercialize it through companies started here in Georgia,” he said.

And that type of transaction pays dividends for Georgia’s economy by boosting employment.

“Aruna has licensed technology from the University of Georgia to commercialize it here in Georgia, creating jobs through that,” he said.

Aruna resides in UGA’s BioBusiness Center and is among the dozens of startup companies arising from research done at state universities. 

The center is part of a network of spaces around the state that are known as business incubators because they nurture young companies. 

Another company at UGA, Pathens Inc., is developing a new way to give a vaccine for tuberculosis. Instead of injecting it, you inhale it.

Fred Quinn, a UGA biology professor and the company’s founder, says it solves a crucial problem for healthcare professionals, especially in areas where most of the two billion cases of tuberculosis are.

“When you’re in rural Africa or Asia, it’s difficult to trek in a thousand needles to inject kids and adults,” he said.

But startups blazing new fields are not the only place where innovation is occurring. The state also has facilities where older companies can re-invent themselves.

One such space is Georgia Tech’s Manufacturing Institute. On a recent afternoon, Stephen Sheffield showed off equipment that creates manufacturing prototypes.

He’s built models for Caterpillar, John Deere and Boeing on projects. And that’s in part because of something many predicted would never happen.

“Manufacturing is coming back, and a lot of companies are coming to us with an interest,” he said.

Indeed what Georgia Tech officials hope will be a ‘manufacturing renaissance’ here and beyond is driving innovation. 

Sheffield helps clients sharpen their competitive edge.

“There are a lot of smaller companies that have new ideas,” he said. “And they’re finding out that if we can improve some of these things, we know can beat some foreign competition and we can bring some work back. And that’s pretty innovative.”

Back at UGA, Swetenburg, the grad student, continues his work. And professor Stice says he’ll help Aruna answer a fundamental question about biology.

“What Raymond’s doing is really trying to figure out is why things happen the way they do,” he said.

And answering that question will help Aruna find more customers, sell more stem cells, and employ more people. And that’s what it’s all about.

 

Next Generation: Robotic Inchworm

Published: November 19, 2012

Researchers use 3D printing to create miniature robots powered by rat cardiac cells that move like caterpillars.

By Sabrina Richards | November 20, 2012

A caterpillar-like robot powered by cardiac cell contractions.Elise A. Corbin.

Device: Researchers used 3D printing technology to create centimeter-long robots, powered by contracting rat cardiac cells, which move by inching along a surface. Published last week (November 15) inScientific Reports, the study clarifies some principles of biobot design, while demonstrating how 3D printing facilitates the process of robot construction.

“The merger of tissue engineering and 3D printing is very exciting,” said Henry Hess, a biomedical engineer at Columbia University who was not involved with the project. 3D printing technology makes fabrication of biobots easy, precise, and reproducible, allowing researchers to concentrate on refining the engineering principles underlying successful biobot design.

In order to make their caterpillar-like biological machine, Rashid Bashir and his colleagues at the University of Illinois at Urbana-Champaign used a 3D printer to lay down thin layers of polymer, similar to contact lens material, upon which they applied a collagen matrix to hold a layer of rat cardiomyocytes. Each polymer/cardiomyocyte layer was placed on a non-elastic base, from which the polymer “legs” extended on either side. The cardiac cells contract spontaneously, providing the force necessary to move the legs of the robots.

The tricky part came when designing the legs themselves, Bashir said. In order to achieve inchworm-like movements, “the back leg has to adhere and the front has to move forward, then the front one has to adhere and the back one has to move forward,” he explained. “So there has to be an asymmetric change in surface adhesion.”

They tested several designs of varying polymer thickness and leg length, which altered how much the force of the beating cardiac cells curled the legs, pulling them away from the surface. Some biobots had legs that couldn’t reach the ground, while others had legs that didn’t release surface tension enough to step forward. The answer came in the form of an asymmetrical design—with one long leg and one short—that resulted in just the right change in adhesion to allow the bots to move forward, said Bashir.

The successful robot, about half a centimeter long, is able to crawl at about a centimeter per minute. “We’ve had [the biobots] going for days to weeks,” as long as the cardiomyocytes can extract nutrients from the liquid medium through which the biobots walk, said Bashir.

What’s New: Though Bashir’s group is not the first to use cardiomyocytes to power tiny biobots, this is the first time scientists have employed 3D printing to facilitate biobot design, said Hess. This technology enables the researchers to predictably create biobots of the right size and shape, which is subject to very specific forces from the cardiac cells, said Bashir.

Importance: Though biobot technology is still in its early days, researchers hope to use biologically-based robots in many future applications, such as sensing and attacking a tumor, or monitoring cancer cells in a patient’s blood, said Roger Kamm, a biological engineer at Massachusetts Institute of Technology who was not involved in the project.

Bashir imagines that his little caterpillar biobots might be able to screen for and target toxins in the environment. He imagines that they could someday be used as biodegradable toxin sensors, able to move toward higher concentrations of water toxins and release neutralizing chemicals to tackle the problem.

Needs Improvement: The current biobots are merely a proof of principle. Though they now can move for weeks while in nutrient-rich media, increasing their size and capabilities or transporting them to toxic environments will require making them less reliant on their environment and more resistant to it, said Kamm. Others in the National Science Foundation-funded collaboration that supported the current research, called Emergent Behavior of Integrated Cellular Systems, are working on microfluidic devices that could provide nutrients to cardiac cells in bigger biobots. Kamm also envisions future bots utilizing many different types of cells: cardiac cells might still provide movement, but perhaps insect cells could be used to create a tough exoskeleton, or plant cells could extract solar energy.

A great challenge will be to create biobots that “live” longer than one cardiomyocyte division, said Hess. “One vision of course is to generate a truly living structure,” he explained. “It could live for 80 years in the same way that a human heart turns over components and lasts for a long time.”

But small steps come first. Now that they’ve demonstrated some guiding principles for their design, Bashir and his colleagues plan to design biological machines that can change direction and climb stairs.

V. Chan et al., “Development of Miniaturized Walking Biological Machines,” Scientific Reports, doi: 10.1038/srep00857, 2012.

Crawling Bio-Robot Runs on Rat Heart Cells

Published: November 18, 2012

Ker Than

for National Geographic News

Published November 19, 2012

A new biological robot has been made from rat heart cells and synthetic materials, a new study says—and the machine could someday lead to others that will attack diseases inside the human body

The centimeter-long "biobot" was made by attaching heart muscle cells onto a flexible structure, or body, of hydrogel—the same material used to make contact lenses for human eyes.

Watch a Video of the Biobot

 

To make the biobot's body, the team used a 3-D printer, which creates solid objects by laying down successive layers of soft materials that fuse together and harden.

Gathering the heart cells was a bit trickier. The researchers removed whole hearts from anesthetized newborn rats, cut the organs into tiny pieces, and then processed the fragments to loosen and separate the heart cells. The cells were then added to the robot body—each bot contains between a few thousand and a few hundred thousand. (Read "Heart Cells Can Regenerate, Nuclear-Bomb Evidence Shows.")

"In a few days they start beating, and the bots start to move," explained study co-author Rashid Bashir, an engineer at the University of Illinois at Urbana-Champaign who helped develop the robot.

As the biobot's "engine," the heart cells' contractions bend the machine's body, causing it to move forward fractions of an inch per second. The biobot has two legs, one that propels it forward and another that acts as a stabilizer.

Heart cells were chosen for the biobot because they spontaneously contract, or "beat," in time with one another, Bashir said by email.

(Also see "Color-Changing Rubber Robot Could Aid Animal Study.")

Biobot Replicates Life

For now, the biobot must be submerged in a nutrient-rich fluid to keep the heart cells alive. But future biological machines could be "fed" via veins.

"Work going on in other labs is aimed at creating vascular systems to meet the metabolic needs of muscles for biobots as they become more developed and grow in scale," said Roger Kamm, a mechanical engineer at MIT who was not involved in the study.

By melding the synthetic and the natural, engineers hope to endow their creations with biological abilities that purely mechanical robots just aren't capable of yet.

"There's a lot that biology does that we just haven't been able to replicate with the inanimate materials that we currently have," Kamm said. "For example, the nose is just a fantastic sensor. We still use dogs in airports to sniff out explosives."

(Pictures: Humanoid robots in National Geographic magazine.)

No Limit to Bio-Robot Uses?

Biobot researchers say there is no limit to the potential uses for their creations.

"You could have crawling or swimming biobots that could sense and migrate towards—and then neutralize—toxic substances," Kamm said.

Similarly, he added, "you could also imagine biobots that function inside the human body and that could sense [chemicals] secreted by tumor cells, migrate through the tissue to the tumor, and secrete substances that destroy it."

But all of that is still far off in the future, study author Bashir cautioned.

"For now we are working on understanding the underlying principles and design rules."

The biobot is detailed in this week's issue of the journal Nature Scientific Reports.

 

3D printed biorobot will enter your gut to track and destroy toxins

Published: November 16, 2012

By Graham Templeton on November 17, 2012 at 9:47 am | 4 Comments

When researchers boast rather casually that making new variations of their invention is as simple as editing a CAD file, we might assume they are talking about a new sort of coffee mug, or perhaps a revolutionary spool for garden hose. Certainly such a simple and cost-effective design process could never give rise to something as complex as a bio-robot, a chimera of industrial gel and living tissue designed to work inside the human body. However, after researchers at the University of Illinois set themselves the task of creating just such a robot, that’s precisely what they did.

Using new, specialized 3D printing technology, engineers were able to deposit a bio-friendly hydrogel into a cantilever design just seven by two millimeters in size, seeded with heart cells from a rat. The cells grew into a matrix and began doing what heart cells do best — beating. By depositing the cells in a particular arrangement throughout the structure, and coaxing them to grow in the desired ways, the beats eventually produced controlled forward movement. After a number of false starts and inferior designs, the researchers were able to build a bio-robot that moved consistently — albeit at only 236 micrometers per second, or 0.00053 miles per hour.

Their workflow allowed the team to create an array of prototypes that they used determine the optimal length and thickness of the biobot’s actuating leg, which provides the power to drive the whole thing forward. In under a dozen prototypes, both CAD-designed and machine-printed, researchers found a working midpoint between the flexibility and strength of the actuating leg, as well as between the stability and size of the support leg.

To put this in perspective, previous attempts at making biological machines have required poured molds or even hand-cut sculptures, and their labor-intensive nature has not allowed the sort of trial and error engineering that has proven so powerful in other industries. Though the result is undeniably simple, it is a working proof of concept for not just biobots, but for bio-printing as well.

Uses for their hydrogel walker are purely speculative at this point, but the team sees potential for the robot to follow a toxin up its concentration gradient toward its source, where antitoxins could be released. In fact, some form of biobot is almost certain to be a large part of the burgeoning field of artificial immune systems. Additionally, while the robot might be small from our perspective, future designs could be plenty strong enough to carry payloads of everything from cell cultures to tracking devices. A tracked biobot released into the gut might stall at a hard-to-find blockage, thus showing physicians where it lies.

Of course, all of these applications are dependent on improving both the speed and lifespan of the biobot. Current designs lose most of their motility after just five days, and while finite lifespan and biodegradable contents are desirable attributes in almost anything released into the body, most jobs will require a more robust robot than that.

Already, the team is working to replace their heart muscle cells with skeletal muscles cells, which are harder to grow but both stronger and easier to control. Integration of specialized neurons should allow some form of sensing of the environment, and a two-legged version would allow more sophisticated steering and locomotion.

These may seem like daunting tasks, but the new approach to design makes even large problems surmountable. When the design process can be iterated in only a few days (and most of that time is spent just letting the cells grow), there’s no telling how soon these biobots might be sliding their way into through bodies, and past our expectations.

____________________________

Read original article at ExtremeTech

3D-Printed Biobots Will Crawl Through Your Body, Targeting Toxins

Published: November 14, 2012

November 15, 2012 at 12:50:00 PM by Sarah Fecht | 1 Comments

3D-printed biobots might one day roam the insides of our bodies, sensing and neutralizing toxins, targeting tumors and releasing drugs, and acting as cellular repairmen. Research published today in Scientific Reports takes a first step toward that goal. 

Engineers from the University of Illinois at Urbana-Champaign used a 3D printer to build several designs for a wormy biobot. They started by printing 5- to 10-millimeter-long a flexible gel scaffold, and seeded it with heart cells from rats. This cardiac tissue spread over the hydrogel in a thin layer, and the cells, powered by a liquid food, beat like a heart to keep the little machine moving. As they alternately flex and relax, the cells move the hydrogel backbone back and forth, resulting in a walking motion. 

For now these biobots won’t win any sprints; they walk about 236 micrometers per second. The research team is working on making them faster and more powerful. And, more excitingly, the team is turning these bots into mobile sensors and responders. 

To do it, engineer Rashid Bashir says the team is trying to replace the biobots’ cardiac muscle with skeletal muscle. (Cardiac cells beat spontaneously, whereas skeletal muscle cells are more controllable.) Then, Bashir says, they’ll incorporate neurons that could detect specific molecules in the environment, such as glucose or a toxin. The neurons could be programmed to send a neurotransmitter to contract the skeletal muscle cells whenever they sense such a toxin, and so could steer the biobot toward its source. Once there, the bot could release a drug or anti-toxin. 

Future biobots might have two legs, enabling them to move forward and backwards, and they might be able to work in the open air where they could help with security and environmental monitoring. Bashir says that 3D printing is a key to the potential of biobots; it means the design is flexible and adaptable for many different purposes. 

Read more: 3D-Printed Biobots Will Crawl Through Your Body, Targeting Toxins - Popular Mechanics

Walking Bio-Bot Made WIth Cells, Gels

Published: November 14, 2012

Humans build autonomous robots all the time, but they tend to be made of metal, plastic and need batteries. Now a team at the University of Illinois has built an antonomous robot made from plastic and living cells. Such a device could be used to detect chemicals in water, climb walls or react to certain elements in the water like a sensor.

Ginormous Armed Robot Controlled by Phone

Engineering Professor Rashid Bashir led a group of scientists that put a layer of heart cells from a rat on one side of a layer of hydrogel. The heart cells, being muscle cells, contract, and bend the whole thing. When they relax, it straightens out. The rhythmic expansion and contractraction allows the so-called bio bot to pull itself along. Because the bio-bot is made of soft plastic and cells, it can be manipulated into shapes that aren't possible with metal. For example, Bashir's group made the polymer into a shape with two appendages — one shaped like a wide square and for support and another shaped into a thin, flat shape that bends. When it "walks" it looks more like a swimming motion.

'Frozen Smoke' To Lend Robots a Light Touch

Another feature is the way it's made: the hydrogel part was made in a 3D printer. By printing robot "parts" this way, it's possible to get a greater variety of shapes. It also means that designing new ones is a much quicker process, since the shaping is done on design software and the materials are simple to work with. The research was published in the journal Scientific Reports. Credit: University of Illinois

BY JESSE EMSPAK

Robots Powered by Rat Heart Cells to Deliver Drugs, Environmental Decontaminants

Published: November 14, 2012

November 15th, 2012 | by Charles Q. Choi

A new biological robot or “bio-bot” made with cells from rat hearts can inch across surfaces like a caterpillar.

Future bio-bots could incorporate neurons to intelligently react to their surroundings.

“You can imagine a bio-bot that can look for toxins in water and then annihilate them,” says researcher Rashid Bashir, a University of Illinois at Urbana-Champaign bioengineer. “They could sense where those toxins are, move toward them and release chemicals that neutralize them, helping in environmental cleanup.”

The investigators developed bio-bots. Each less than a centimeter long, using 3-D printers that laid down layers of living cells and other materials on top of each other, much like ordinary printers would lay down layers of ink on paper. Scientists are increasingly using 3-D printers to manufacture a dazzling variety of robotic devices

The researchers first used 3-D printers to create scaffolds for the living cells. These platforms were made of a hydrogel similar to the material used to produce soft contact lenses.

The 3-D printers extrude the scaffolds layer by layer, solidifying each with ultraviolet lasers before depositing the next. In the end, the scaffolds each resemble a stick of gum with a rectangular block sticking out from it. 

Living cells from rat hearts are then printed onto the scaffold on either side of this rectangular block and immersed in a nutrient bath that keeps them alive for three to five days. These heart cells simultaneously contract, making the scaffold flex under them.

The rectangular block on the bio-bot’s scaffold does not sit directly in the device’s middle. Rather, it lies slightly closer to one of its ends. This ensures that one end or “leg” of the scaffold has more rat cells on it, meaning that it bends more than the other side when the cells contract. This asymmetry gives bio-bots directed movement. If the rectangular block were in the middle, both of the robot’s ends would bend equally, resulting in it essentially going nowhere.

The side of the bio-bot with more rat cells on it serves as its propelling leg, providing that it has enough friction to grip the surface it is moving on. The bio-bots can propel themselves forward at speeds up to roughly 236 microns per second. (The average human hair is about 100 microns wide.) This movement amounts to a little more than a half-inch per minute.

“The resulting actuation and movement is very promising, and we will work to improve the designs further,” Bashir says. He and his colleagues detailed their findings onlineNov. 15 in the journal Scientific Reports.

 

The next step could involve tinkering with the bio-bot scaffolds to grant them novel capabilities. For instance, scientists could tailor the hydrogel that comprises the scaffolds to release certain molecules in response to any of a wide range of stimuli, such as acidity or temperature. These molecules might include vital nutrients or growth factors to keep the cells alive, or drugs that increase or decrease cell movements to alter bio-bot speed.

A more advanced form of control over the units could involve giving them neurons, Bashir says. For instance, researchers could engineer clusters of sensory neurons that can both monitor the environment and trigger bio-bot movements.

“What I find most interesting and exciting about this work is the potential to construct systems that are steerable and can be combined with other cell types to sense their environment and move in response to it,” says bioengineer Roger Kamm at MIT, who did not take part in this research.

Bio-bots also could have a wide range of applications in the body or in the lab, Bashir says. For instance, bio-bots might help deliver life-saving medicines within a person, or be used to mimic organs like hearts to help test potential pharmaceuticals.

“The goal is to build biological machines using cells as building blocks,” Bashir says.

He stressed that his team is still working on the technology. “What we have now are just building blocks for more complex systems that can eventually be used for the benefit of humankind,” he says.

Top Image: Courtesy Elise A. Corbin. (Courtesy Vincent Chan)
 

Charles Q. Choi has written for Scientific American, The New York Times, Wired, Science and Nature, among others. In his spare time, he has traveled to all seven continents, including scaling the side of an iceberg in Antarctica, investigating mummies from Siberia, snorkeling in the Galapagos, climbing Mt. Kilimanjaro, camping in the Outback, avoiding thieves near Shaolin Temple and hunting for mammoth DNA in Yukon.

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The team that developed the "bio-bots" – from left, Taher Saif, Vincent Chan, Hyun Joon Kong, Rashid Bashir, Kidong Park and Mitchell Collens. | Photo by L. Brian Stauffer

These bots were made for walking: Cells power biological machines

Published: November 14, 2012

 

 |VIEW VIDEO

 

 

11/15/2012 | Liz Ahlberg, Physical Sciences Editor | 217-244-1073; eahlberg@illinois.edu

CHAMPAIGN, Ill. — They’re soft, biocompatible, about 7 millimeters long – and, incredibly, able to walk by themselves. Miniature “bio-bots” developed at the University of Illinois are making tracks in synthetic biology.

Designing non-electronic biological machines has been a riddle that scientists at the interface of biology and engineering have struggled to solve. The walking bio-bots demonstrate the Illinois team’s ability to forward-engineer functional machines using only hydrogel, heart cells and a 3-D printer.

With an altered design, the bio-bots could be customized for specific applications in medicine, energy or the environment. The research team, led by U. of I. Professor Rashid Bashir, published its results in the journal Scientific Reports.

“The idea is that, by being able to design with biological structures, we can harness the power of cells and nature to address challenges facing society,” said Bashir, an Abel Bliss Professor of Engineering. “As engineers, we’ve always built things with hard materials, materials that are very predictable. Yet there are a lot of applications where nature solves a problem in such an elegant way. Can we replicate some of that if we can understand how to put things together with cells?”

The key to the bio-bots’ locomotion is asymmetry. Resembling a tiny springboard, each bot has one long, thin leg resting on a stout supporting leg. The thin leg is covered with rat cardiac cells. When the heart cells beat, the long leg pulses, propelling the bio-bot forward.

The team uses a 3-D printing method common in rapid prototyping to make the main body of the bot from hydrogel, a soft gelatin-like polymer. This approach allowed the researchers to explore various conformations and adjust their design for maximum speed. The ease of quickly altering design also will allow them to build and test other configurations with an eye toward potential applications.

For example, Bashir envisions the bio-bots being used for drug screening or chemical analysis, since the bots’ motion can indicate how the cells are responding to the environment. By integrating cells that respond to certain stimuli, such as chemical gradients, the bio-bots could be used as sensors.

“Our goal is to see if we can get this thing to move toward chemical gradients, so we could eventually design something that can look for a specific toxin and then try to neutralize it,” said Bashir, who also is a professor of electrical and computer engineering, and of bioengineering

“Now you can think about a sensor that’s moving and constantly sampling and doing something useful, in medicine and the environment. The applications could be many, depending on what cell types we use and where we want to go with it.”

Next, the team will work to enhance control and function, such as integrating neurons to direct motion or cells that respond to light. They are also working on creating robots of different shapes, different numbers of legs, and robots that could climb slopes or steps.

“The idea here is that you can do it by forward-engineering,” said Bashir, who is the director of the Micro and Nanotechnology Laboratory. “We have the design rules to make these millimeter-scale shapes and different physical architectures, which hasn’t been done with this level of control. What we want to do now is add more functionality to it.”

“I think we are just beginning to scratch the surface in this regard,” said graduate student Vincent Chan, first author of the paper. “That is what’s so exciting about this technology – to be able to exploit some of nature’s unique capabilities and utilize it for other beneficial purposes or functions.”

The National Science Foundation supported this work through a Science and Technology Center (Emergent Behavior of Integrated Cellular Systems) grant. Graduate student Mitchell Collens, postdoctoral researcher Kidong Park, chemical and biological engineering professorHyunjoon Kong, and mechanical science and engineering professor Taher Saif were co-authors of the paper. Bashir also is affiliated with the Frederick Seitz Materials Research Laboratory and the Institute for Genomic Biology at the U. of I.

Caption: The team that developed the "bio-bots" – from left, Taher Saif, Vincent Chan, Hyun Joon Kong, Rashid Bashir, Kidong Park and Mitchell Collens. | Photo by L. Brian Stauffer

Genetic Packing: Successful Stem Cell Differentiation Requires DNA Compaction, Study Finds

Published: May 8, 2012

New research findings show that embryonic stem cells unable to fully compact the DNA inside them cannot complete their primary task: differentiation into specific cell types that give rise to the various types of tissues and structures in the body.

Researchers from the Georgia Institute of Technology and Emory University found that chromatin compaction is required for proper embryonic stem cell differentiation to occur. Chromatin, which is composed of histone proteins and DNA, packages DNA into a smaller volume so that it fits inside a cell.

A study published on May 10, 2012 in the journal PLoS Genetics found that embryonic stem cells lacking several histone H1 subtypes and exhibiting reduced chromatin compaction suffered from impaired differentiation under multiple scenarios and demonstrated inefficiency in silencing genes that must be suppressed to induce differentiation.

“While researchers have observed that embryonic stem cells exhibit a relaxed, open chromatin structure and differentiated cells exhibit a compact chromatin structure, our study is the first to show that this compaction is not a mere consequence of the differentiation process but is instead a necessity for differentiation to proceed normally,” said Yuhong Fan, an assistant professor in the Georgia Tech School of Biology.

Fan and Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, led the study with assistance from Georgia Tech graduate students Yunzhe Zhang and Kaixiang Cao, research technician Marissa Cooke, and postdoctoral fellow Shiraj Panjwani.

The work was supported by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS), the National Science Foundation, a Georgia Cancer Coalition Distinguished Scholar Award, and a Johnson & Johnson/Georgia Tech Healthcare Innovation Award.

Phase contrast images showing that H1 triple-knockout (bottom) embryonic stem cells were unable to adequately form neurites and neural networks compared to wild-type embryonic stem cells (top). (Click image for high-resolution version. Credit: Yuhong Fan)

To investigate the impact of linker histones and chromatin folding on stem cell differentiation, the researchers used embryonic stem cells that lacked three subtypes of linker histone H1 — H1c, H1d and H1e — which is the structural protein that facilitates the folding of chromatin into a higher-order structure. They found that the expression levels of these H1 subtypes increased during embryonic stem cell differentiation, and embryonic stem cells lacking these H1s resisted spontaneous differentiation for a prolonged time, showed impairment during embryoid body differentiation and were unsuccessful in forming a high-quality network of neural cells.

“This study has uncovered a new, regulatory function for histone H1, a protein known mostly for its role as a structural component of chromosomes,” said Anthony Carter, who oversees epigenetics grants at NIGMS.  “By showing that H1 plays a part in controlling genes that direct embryonic stem cell differentiation, the study expands our understanding of H1’s function and offers valuable new insights into the cellular processes that induce stem cells to change into specific cell types.”

During spontaneous differentiation, the majority of the H1 triple-knockout embryonic stem cells studied by the researchers retained a tightly packed colony structure typical of undifferentiated cells and expressed high levels of Oct4 for a prolonged time. Oct4 is a pluripotency gene that maintains an embryonic stem cell’s ability to self-renew and must be suppressed to induce differentiation.

“H1 depletion impaired the suppression of the Oct4 and Nanog pluripotency genes, suggesting a novel mechanistic link by which H1 and chromatin compaction may mediate pluripotent stem cell differentiation by contributing to the epigenetic silencing of pluripotency genes,” explained Fan. “While a significant reduction in H1 levels does not interfere with embryonic stem cell self-renewal, it appears to impair differentiation.”

Immunostaining of wild-type (top) and H1 triple-knockout (bottom) cultures under a neural differentiation protocol. The H1 triple-knockout cells were defective in forming neuronal and glial cells and a neural network, which is essential for nervous system development. (Click image for high-resolution version. Credit: Yuhong Fan)

The researchers also used a rotary suspension culture method developed by McDevitt to produce with high efficiency homogonous 3D clumps of embryonic stem cells called embryoid bodies. Embryoid bodies typically contain cell types from all three germ layers — the ectoderm, mesoderm and endoderm — that give rise to the various types of tissues and structures in the body. However, the majority of the H1 triple-knockout embryoid bodies formed in rotary suspension culture lacked differentiated structures and displayed gene expression signatures characteristic of undifferentiated stem cells.

“H1 triple-knockout embryoid bodies displayed a reduced level of activation of many developmental genes and markers in rotary culture, suggesting that differentiation to all three germ layers was affected.” noted McDevitt.

The embryoid bodies also lacked the epigentic changes at the pluripotency genes necessary for differentiation, according to Fan.

“When we added one of the deleted H1 subtypes to the embryoid bodies, Oct4 was suppressed normally and embryoid body differentiation continued,” explained Fan. “The epigenetic regulation of Oct4 expression by H1 was also evident in mouse embryos.”

In another experiment, the researchers provided an environment that would encourage embryonic stem cells to differentiate into neural cells. However, the H1 triple-knockout cells were defective in forming neuronal and glial cells and a neural network, which is essential for nervous system development. Only 10 percent of the H1 triple-knockout embryoid bodies formed neurites and they produced on average eight neurites each. In contrast, half of the normal embryoid bodies produced, on average, 18 neurites.

In future work, the researchers plan to investigate whether controlling H1 histone levels can be used to influence the reprogramming of adult cells to obtain induced pluripotent stem cells, which are capable of differentiating into tissues in a way similar to embryonic stem cells.

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under award number GM085261 and the National Science Foundation under award number CBET-0939511. The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NIH or NSF.

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Image caption: Hematoxylin and eosin (H&E) staining of sections of wild-type (top row) and H1 triple-knockout (bottom row) embryoid bodies. After 14 days in rotary suspension culture, the wild-type embryoid bodies showed more differentiated morphologies with cysts forming (black arrows) and the knockout embryoid bodies failed to form cavities (far right). (Click image for high-resolution version. Credit: Yuhong Fan)

Paula Hammond, the David H. Koch Professor in Engineering, right, with postdoc Jinkee Hong. Photo: Allegra Boverman

Delivering RNA with tiny sponge-like spheres

Published: February 25, 2012

For the past decade, scientists have been pursuing cancer treatments based on RNA interference— a phenomenon that offers a way to shut off malfunctioning genes with short snippets of RNA. However, one huge challenge remains: finding a way to efficiently deliver the RNA.

Most of the time, short interfering RNA (siRNA) — the type used for RNA interference — is quickly broken down inside the body by enzymes that defend against infection by RNA viruses.

Paula Hammond, the David H. Koch Professor in Engineering, right, with postdoc Jinkee Hong. (Photo: Allegra Boverman)

“It’s been a real struggle to try to design a delivery system that allows us to administer siRNA, especially if you want to target it to a specific part of the body,” says Paula Hammond, the David H. Koch Professor in Engineering at MIT.

Hammond and her colleagues have now come up with a novel delivery vehicle in which RNA is packed into microspheres so dense that they withstand degradation until they reach their destinations. The new system, described Feb. 26 in the journal Nature Materials, knocks down expression of specific genes as effectively as existing delivery methods, but with a much smaller dose of particles.

Such particles could offer a new way to treat not only cancer, but also any other chronic disease caused by a “misbehaving gene,” says Hammond, who is also a member of MIT’s David H. Koch Institute for Integrative Cancer Research. “RNA interference holds a huge amount of promise for a number of disorders, one of which is cancer, but also neurological disorders and immune disorders,” she says..

Lead author of the paper is Jong Bum Lee, a former postdoc in Hammond’s lab. Postdoc Jinkee Hong, Daniel Bonner PhD ’12 and Zhiyong Poon PhD ’11 are also authors of the paper.

Genetic disruption

RNA interference is a naturally occurring process, discovered in 1998, that allows cells to fine-tune their genetic expression. Genetic information is normally carried from DNA in the nucleus to ribosomes, cellular structures where proteins are made. siRNA binds to the messenger RNA that carries this genetic information, destroying instructions before they reach the ribosome.

A cluster of microsponges made of long strands of folded RNA, as seen by scanning electron microscopy.

Scientists are working on many ways to artificially replicate this process to target specific genes, including packaging siRNA into nanoparticles made of lipids or inorganic materials such as gold. Though many of those have shown some success, one drawback is that it’s difficult to load large amounts of siRNA onto those carriers, because the short strands do not pack tightly.

To overcome this, Hammond’s team decided to package the RNA as one long strand that would fold into a tiny, compact sphere. The researchers used an RNA synthesis method known as rolling circle transcription to produce extremely long strands of RNA made up of a repeating sequence of 21 nucleotides. Those segments are separated by a shorter stretch that is recognized by the enzyme Dicer, which chops RNA wherever it encounters that sequence.

As the RNA strand is synthesized, it folds into sheets that then self-assemble into a very dense, sponge-like sphere. Up to half a million copies of the same RNA sequence can be packed into a sphere with a diameter of just two microns. Once the spheres form, the researchers wrap them in a layer of positively charged polymer, which induces the spheres to pack even more tightly (down to a 200-nanometer diameter) and also helps them to enter cells.

After the spheres enter a cell, the Dicer enzyme chops the RNA at specific locations, releasing the 21-nucleotide siRNA sequences. 

Peixuan Guo, director of the NIH Nanomedicine Development Center at the University of Kentucky, says the most exciting aspect of the work is the development of a new self-assembly method for RNA particles. Guo, who was not part of the research team, adds that the particles might be more effective at entering cells if they were shrunk to an even smaller size, closer to 50 nanometers.xxx
Targeting tumors

In the Nature Materials paper, the researchers tested their spheres by programming them to deliver RNA sequences that shut off a gene that causes tumor cells to glow in mice. They found that they could achieve the same level of gene knockdown as conventional nanoparticle delivery, but with about one-thousandth as many particles.

The microsponges accumulate at tumor sites through a phenomenon often used to deliver nanoparticles: The blood vessels surrounding tumors are “leaky,” meaning that they have tiny pores through which very small particles can squeeze. 

In future studies, the researchers plan to design microspheres coated with polymers that specifically target tumor cells or other diseased cells. They are also working on spheres that carry DNA, for potential use in gene therapy.

Constructing Biological Machines: Research has implications for industry, medicine, energy, environment

Published: January 18, 2012

By Marlene Cimons, National Science Foundation

Imagine clusters of living cells that behave like “machines,” doing many jobs that today’s standard mechanical devices cannot perform, or doing them better.

For example, picture a collection of neurons that signals when a plant needs water. Or an “organ,” made up of cells implanted under the skin, that senses when someone’s blood pressure is too high, then dispenses a drug to lower it. Or a “nose” that crawls into a tiny space and detects a toxin in the water supply, or a hidden explosive.

A science fiction fantasy? Not necessarily.

“We want to create a new biology to, for the first time, build biological machines made purely from cells, whether human cells or those from other animals and organisms,” says Roger D. Kamm, professor of biological and mechanical engineering at the Massachusetts Institute of Technology, and director of the Center for Emergent Behaviors of Integrated Cellular Systems. “We’re not trying to make something that nature already makes very well, but we want to take advantage of what nature has developed over the years, and improve upon it, or use it for other purposes."

The idea behind the center’s research is to understand cells and their environment, and how these cells work together to incorporate biochemical and mechanical cues to perform a wide variety of functions. The center’s approach for constructing biological machines is similar to the engineering techniques employed in making non-biological machines. “Many members of our team are engineers, and we think like engineers, building machines up from individual parts,” Kamm says.

The center, which is based at MIT, is a National Science Foundation (NSF) Science and Technology Center, with research partners at the University of Illinois at Urbana-Champaign, the Georgia Institute of Technology and minority-serving partners at City College of New York, University of California at Merced, and Morehouse College. NSF is funding the Center with $5 million annually over five years.

If successful, the research could have dramatic applications in industry, medicine, energy and the environment, among others. “Just like you can use gears, motors, and sensors, for example, in making a conventional machine, you can use their biological equivalents for a cell-based one,” Kamm says.

Biological robots in an assembly line, for example, could repair themselves and adapt to optimize their performance; new “organs” could be designed and implanted, with the ability to sense drug or glucose levels in the bloodstream, and respond appropriately by turning on or off drug secretion; organisms could swim to an oil spill, and “eat” the damaging substance, replicate if needed, then swim home to the “host” ship for processing; “smart” plant-based machines could release the correct amount of controlled energy to produce heat, light or mechanical work.

“Your imagination could run wild with this once you start thinking of the possibilities,” Kamm says. “Much of what we are planning to do may sound way out there, and futuristic, but we can already accomplish many of the individual steps. For example, we can make a collection of muscle cells contract on demand. The next challenge is to figure out how to keep these cells functioning collectively as a muscle. Right now the cells will start to lose their muscle-like characteristics, and become unable to function."

To be sure, the idea of creating living systems with important new roles raises certain ethical issues which center scientists plan to address.

“Will these machines be endowed with the capability to self-repair, adapt, and self-replicate?” Kamm says. “If so, they become indistinguishable from natural organisms and need to be considered in a similar light. If stem cells are used, from what source may they be taken? What protections and regulations need to be in place? These and many other questions will be openly debated within the center, and with the larger community as we develop these advancing technologies.’’

Center researchers have five projects currently underway. Three of the projects focus on developing machine components and enabling technologies--the methods that will allow the assembly of machines. In addition, the scientists are developing two cellular machines. One of them will be able to sense glucose in the bloodstream and dispense insulin as needed. They also are working on creating millimeter scale biological machines made from polymers and living cells, possibly cardiac or skeletal muscle cells that can identify a chemical toxin, move toward it, and release chemicals to neutralize it. Similarly, another project will release machines that can inspect produce, searching for pathogens, and signal whether they have found any.

Center researchers’ long-term goal is to explore ways to construct robotics from cells. “What would be the advantage of a biological robotic arm? It could remodel itself if its task changes, so it can perform the task better, and can repair itself,” Kamm says. “If I wanted to become a professional tennis player, for example, and I started to train and work out, my arm would remodel itself and perform the task better over time. That’s the idea.”

While the obstacles are still considerable, biological machines may be closer than most people believe. “Our hope is to create several simple biological machines within the next five years,” Kamm says. “And, during that same time period, we also expect that industry will begin to recognize the potential, and initiate its own research and development programs that will speed things along even more.”

Team designs a bandage that spurs, guides blood vessel growth

Published: December 13, 2011

CHAMPAIGN, lll. — Researchers have developed a bandage that stimulates and directs blood vessel growth on the surface of a wound. The bandage, called a “microvascular stamp,” contains living cells that deliver growth factors to damaged tissues in a defined pattern. After a week, the pattern of the stamp “is written in blood vessels,” the researchers report.

 

After the stamp is removed its pattern is revealed in the pattern of blood vessels below. | Photo courtesy Micro and Nanotechnology Lab After the stamp is removed its pattern is revealed in the pattern of blood vessels below. | Photo courtesy Micro and Nanotechnology Lab

A paper describing the new approach will appear as the January 2012 cover article of the journal Advanced Materials.

“Any kind of tissue you want to rebuild, including bone, muscle or skin, is highly vascularized,” said University of Illinois chemical and biomolecular engineering professor Hyunjoon Kong, a co-principal investigator on the study with electrical and computer engineering professor Rashid Bashir. “But one of the big challenges in recreating vascular networks is how we can control the growth and spacing of new blood vessels.”

“The ability to pattern functional blood vessels at this scale in living tissue has not been demonstrated before,” Bashir said. “We can now write features in blood vessels.”

Other laboratories have embedded growth factors in materials applied to wounds in an effort to direct blood vessel growth. The new approach is the first to incorporate live cells in a stamp. These cells release growth factors in a more sustained, targeted manner than other methods, Kong said.

The stamp is nearly 1 centimeter across and is built of layers of a hydrogel made of polyethylene glycol (an FDA-approved polymer used in laxatives and pharmaceuticals) and methacrylic alginate (an edible, Jell-O-like material).

The stamp is porous, allowing small molecules to leak through, and contains channels of various sizes to direct the flow of larger molecules, such as growth factors.

The researchers tested the stamp on the surface of a chicken embryo. After a week the stamp was removed, revealing a network of new blood vessels that mirrored the pattern of the channels in the stamp.

“This is a first demonstration that the blood vessels are controlled by the biomaterials,” Kong said.

The researchers see many potential applications for the new stamp, from directing the growth of blood vessels around a blocked artery, to increasing the vascularization of tissues with poor blood flow, to “normalizing” blood vessels that feed a tumor to improve the delivery of anti-cancer drugs. Enhancing the growth of new blood vessels in a coordinated pattern after surgery may also reduce recovery time and lessen the amount of scar tissue, the researchers said.

In another study published earlier this year, the team developed a biodegradable material that supports living cells. Future research will test whether the new material also can be used as a stamp.

Researchers on the study team also included K. Jimmy Hsia, a professor of mechanical science and engineering and of bioengineering at Illinois; postdoctoral researchers Jae Hyun Jeong and Pinar Zorlutuna; and graduate students Vincent Chan, Chaenyung Cha and Casey Dyck.

This study was supported in part by the National Science Foundation Emergent Behaviors of Integrated Cellular Systems Center at Illinois, Georgia Institute of Technology and Massachusetts Institute of Technology; the U.S. Army Telemedicine and Advanced Technology Research Center; an NSF Career grant; the American Heart Association; and the Amore Pacific Corp.

Bashir, the Abel Bliss Professor of Engineering, also is a professor of bioengineering. He and Kong are affiliates of the Micro and Nanotechnology Lab and the Institute for Genomic Biologyat Illinois.

Editor's note: To contact Hyunjoon Kong, call 217-333-1178; email hjkong06@illinois.edu.
To reach Rashid Bashir, email rbashir@illinois.edu.

The paper, “Living Microvascular Stamp for Patterning of Functional Neovessels; Orchestrated Control of Matrix Property and Geometry,” is available online.

 

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