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Friday, November 30th, 2012
| Time | Event |
| 5:00a | Precisely engineering 3-D brain tissues Borrowing from microfabrication techniques used in the semiconductor industry, MIT and Harvard Medical School (HMS) engineers have developed a simple and inexpensive way to create three-dimensional brain tissues in a lab dish. The new technique yields tissue constructs that closely mimic the cellular composition of those in the living brain, allowing scientists to study how neurons form connections and to predict how cells from individual patients might respond to different drugs. The work also paves the way for developing bioengineered implants to replace damaged tissue for organ systems, according to the researchers. “We think that by bringing this kind of control and manipulation into neurobiology, we can investigate many different directions,” says Utkan Demirci, an assistant professor in the Harvard-MIT Division of Health Sciences and Technology (HST). Demirci and Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT’s Media Lab and McGovern Institute, are senior authors of a paper describing the new technique, which appears in the Nov. 27 online edition of the journal Advanced Materials. The paper’s lead author is Umut Gurkan, a postdoc at HST, Harvard Medical School and Brigham and Women’s Hospital. ‘Unique challenges’ Although researchers have had some success growing artificial tissues such as liver or kidney, “the brain presents some unique challenges,” Boyden says. “One of the challenges is the incredible spatial heterogeneity. There are so many kinds of cells, and they have such intricate wiring.” Brain tissue includes many types of neurons, including inhibitory and excitatory neurons, as well as supportive cells such as glial cells. All of these cells occur at specific ratios and in specific locations. To mimic this architectural complexity in their engineered tissues, the researchers embedded a mixture of brain cells taken from the primary cortex of rats into sheets of hydrogel. They also included components of the extracellular matrix, which provides structural support and helps regulate cell behavior. Those sheets were then stacked in layers, which can be sealed together using light to crosslink hydrogels. By covering layers of gels with plastic photomasks of varying shapes, the researchers could control how much of the gel was exposed to light, thus controlling the 3-D shape of the multilayer tissue construct. This type of photolithography is also used to build integrated circuits onto semiconductors — a process that requires a photomask aligner machine, which costs tens of thousands of dollars. However, the team developed a much less expensive way to assemble tissues using masks made from sheets of plastic, similar to overhead transparencies, held in place with alignment pins. The tissue cubes can be made with a precision of 10 microns, comparable to the size of a single cell body. At the other end of the spectrum, the researchers are aiming to create a cubic millimeter of brain tissue with 100,000 cells and 900 million connections. The new system is the first that includes all of the necessary features for building useful 3-D tissues: It is inexpensive, precise, and allows complex patterns to be generated, says Metin Sitti, a professor of mechanical engineering at Carnegie Mellon University. “Many people could easily use this method for creating heterogeneous, complex gel structures,” says Sitti, who was not part of the research team. Answering fundamental questions Because the tissues include a diverse repertoire of brain cells, occurring in the same ratios as they do in natural brain tissue, they could be used to study how neurons form the connections that allow them to communicate with each other. “In the short term, there's a lot of fundamental questions you can answer about how cells interact with each other and respond to environmental cues,” Boyden says. As a first step, the researchers used these tissue constructs to study how a neuron’s environment might constrain its growth. To do this, they placed single neurons in gel cubes of different sizes, then measured the cells’ neurites, long extensions that neurons use to communicate with other cells. It turns out that under these conditions, neurons get “claustrophobic,” Demirci says. “In small gels, they don't necessarily send out as long neurites as they would in a five-times-larger gel.” In the long term, the researchers hope to gain a better understanding of how to design tissue implants that could be used to replace damaged tissue in patients. Much research has been done in this area, but it has been difficult to figure out whether the new tissues are correctly wiring up with existing tissue and exchanging the right kinds of information. Another long-term goal is using the tissues for personalized medicine. One day, doctors may be able to take cells from a patient with a neurological disorder and transform them into induced pluripotent stem cells, then induce these constructs to grow into neurons in a lab dish. By exposing these tissues to many possible drugs, “you might be able to figure out if a drug would benefit that person without having to spend years giving them lots of different drugs,” Boyden says. Other authors of the paper are Yantao Fan, a visiting graduate student at HMS and HST; Feng Xu and Emel Sokullu Urkac, postdocs at HMS and HST; Gunes Parlakgul, a visiting medical student at HMS and HST; MIT graduate students Jacob Bernstein and Burcu Erkmen; and Wangli Xing, a professor at Tsinghua University. The research was funded by the National Science Foundation, the Paul Allen Family Foundation, the New York Stem Cell Foundation, the National Institutes of Health, the Institute of Engineering and Technology A.F. Harvey Prize, and MIT Lincoln Laboratory. EVENT: As part of the MIT News at Noon program, Burcu Erkmen will speak about this research at the MIT Museum on Friday, Dec. 7, from 12:10 to 12:50 p.m. Learn more |
| 5:00a | The robotic equivalent of a Swiss army knife The little device is called a milli-motein — a name melding its millimeter-sized components and a motorized design inspired by proteins, which naturally fold themselves into incredibly complex shapes. This minuscule robot may be a harbinger of future devices that could fold themselves up into almost any shape imaginable. The device was conceived by Neil Gershenfeld, head of MIT’s Center for Bits and Atoms, visiting scientist Ara Knaian and postdoctoral associate Kenneth Cheung, and is described in a paper presented recently at the 2012 Intelligent Robots and Systems conference. Its key feature, Gershenfeld says: “It’s effectively a one-dimensional robot that can be made in a continuous strip, without conventionally moving parts, and then folded into arbitrary shapes.” To build the world’s smallest chain robot, the team had to invent an entirely new kind of motor: not only small and strong, but also able to hold its position firmly even with power switched off. The researchers met these needs with a new system called an electropermanent motor. The motor is similar in principle to the giant electromagnets used in scrapyards to lift cars, in which a powerful permanent magnet (one that, like an ordinary bar magnet, requires no power) is paired with a weaker magnet (one whose magnetic field direction can be flipped by an electric current in a coil). The two magnets are designed so that their fields either add or cancel, depending on which way the switchable field points. Thus, the force of the powerful magnet can be turned off at will — such as to release a suspended car — without having to power an enormous electromagnet the whole time.  A four-segment milli-motein chain with a one-centimeter module size. Photo: MIT Center for Bits and Atoms The milli-motein concept follows up on a paper, published last year, which examined the theoretical possibility of assembling any desired 3-D shape simply by folding a long string of identical subunits. That paper, co-authored by Cheung, MIT professor Erik Demaine, alumnus Saul Griffith, and former Computer Science and Artificial Intelligence Laboratory research scientist Jonathan Bachrach, proved mathematically that it was possible for any 3-D shape to be reproduced by folding a sufficiently long string — and that it’s possible to figure out how to fold such a string, and the exact steps needed to successfully reach the desired endpoint. “We showed that you could make such a universal system that’s very simple,” Cheung says. While he and his colleagues have not yet proved a way of always finding the optimal path to a given folded shape, they did find several useful strategies for arriving at practical folding sequences. Demaine points out that the folding of the shape doesn’t have to be sequential, moving along the string one joint at a time. “Ideally, you’d like to do it all at once,” he says, with each of the joints folding themselves to the desired configuration simultaneously so that the loads are distributed. Other researchers, including some at MIT, have explored the idea of fashioning reconfigurable robots from a batch of separate pieces that could self-assemble into different configurations — an approach sometimes called “programmable pebbles.” But Gershenfeld’s team found that a string of subunits capable of folding itself into any shape could be simpler in terms of control, power and communications than using separate pieces that must find each other and assemble in the right order. “You can just pass signals down the chain,” Knaian says. It’s part of an overall approach, Gershenfeld explains, to “turning data into things.” In an article in the current issue of the magazine Foreign Affairs, he describes a technology roadmap for accomplishing that, and its policy implications. He and his colleagues have established a global network of more than 100 “fab labs” that provide community access to computer-controlled fabrication tools. Today, the design information is contained in an external computer rather than in the materials being manufactured, but the research goal is to digitize the materials themselves so that they can ultimately change their own shape, as the milli-motein does. Hod Lipson, an associate professor of mechanical and aerospace engineering and computing and information science at Cornell University, says, "This result brings us closer to the idea of programmable matter — where computer programs and materials merge to form a new kind of matter whose shape and function can be programmed — not unlike biology. Many people are excited today to learn about 3-D printing and its ability to fabricate any shape; Gershenfeld’s group is already thinking about the next episode, where we don’t just control the shape of objects, but also their behavior." The milli-motein is part of a family of such devices being explored at size scales ranging from protein-based “nanoassemblers” to a version where the chain is as big as a person, Gershenfeld says. Ultimately, a reconfigurable robot should be “small, cheap, durable and strong,” Knaian says, adding that right now, “it’s not possible to get all of those.” Still, he points out, “Biology is the existence proof that it is possible.” The MIT researchers’ work could lead to robotic systems that can be dynamically reconfigured to do many different jobs rather than repeating a fixed function, and that can be produced much more cheaply than conventional robotics. The development of the milli-motein included recent graduate Maxim Lobovsky SM '11 and undergraduate students Asa Oines and Peter Schmidt-Neilsen (who worked on the project as visiting high-school students). The work was supported by the U.S. Defense Advanced Research Projects Agency’s Maximum Mobility and Manipulation and Programmable Matter projects. |
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