#Big step in battling bladder disease The millions of people worldwide who suffer from the painful bladder disease known as interstitial cystitis (IC) may soon have a better, long-term treatment option, thanks
to a controlled-release, implantable device invented by MIT professor Michael Cima and other researchers.
In the mid-2000s, a urologist at Boston Children Hospital contacted Cima at the behest of Institute Professor Robert Langer with a plea:
Could he develop an alternative treatment for IC? Treating the debilitating disease which causes painful and frequent urination that can interrupt daily life currently requires infusing the drug lidocaine into a patient bladder through a catheter.
This provides temporary relief and must be repeated frequently. ou hear that and you say, here has to be a better way,?
says Cima, the David H. Koch Professor of Engineering. Rising to the challenge, Cima and engineering student Heejin Lee SM 4, Phd 9 invented a solution:
a pretzel-shaped silicone tube that could be inserted into the bladder, slowly releasing lidocaine over two weeks.
Equipped with shape-memory wire, the tube could be straightened to fit into a catheter and spring back into its pretzel shape in the bladder,
preventing it from being expelled during urination. Since 2009, the platform which was detailed in a 2010 issue of the Journal of Controlled Release has been developed to carry lidocaine
and tested in clinical trials by Taris Biomedical, co-founded by Cima and Langer, a longtime collaborator and entrepreneur.
Last month, pharmaceutical giant Allergan bought the worldwide rights to that specific device called Liris (for lidocaine-releasing intravesical system), for $69 million up front and what could total more than $600 million in milestone payments.
Allergan is prepping for phase-three clinical trials for Liris, which can deliver 400 milligrams of lidocaine to patients.
Because the device stays in the bladder so long, it also allows for smaller doses, reducing adverse reactions.)
But Taris now plans to tailor the platform device to carry other drugs into the bladder to treat various diseases,
including bladder cancer. rology hasn gotten really the benefit of improvement in the biotech revolution. This type of technology can revolutionize how we do drug therapy in urology,
says Cima, who serves on Tarisboard of directors. Taris taking shape Liris started as Lee Phd thesis under the tutelage of Cima and with a grant from the MIT Deshpande Center for Technological Innovation
along with several MIT graduate students, to test much smaller versions of the device in animals. he Deshpande funding was an absolutely critical element in getting the data necessary to raise capital for Taris,
Indeed, collecting clinical data is a major challenge in spinning biotechnology out of the lab, notes Cima,
who has founded four other companies in his time at MIT Microchips Inc.,Springleaf Therapeutics, Entra Pharmaceuticals,
the researchers developed a prototype device by using a laser to cut a hole in a silicone tube to add drugs. ight
laughing. remember Heejin came into my office thinking his thesis was about to go out the window.
because the obvious solution doesn work.?Heejin then redesigned the device as a pretzel-shaped structure by incorporating a superelastic wire made from a special nitinol alloy.
This structure is threaded into a catheter, and inserted into the bladder. When expelled from the catheter,
the device returns to a pretzel shape and floats freely. The researchers found that the pretzel shape still used in today devices was critical for retention in the bladder,
as it prevents the device from simple expulsion through the urethra when the bladder contracts.
Thanks to the data gathered from the study, Cima and Langer were able to launch Taris, with Lee as chief scientist,
with $15 million in funding to enter phase-one clinical trials. Taris would go on to earn $30 million in subsequent funding rounds.
t was a big unmet need, Langer says of his decision to co-found Taris;
and some of the students had done the work, collected the data to determine it was thought feasible,
I it was something that could make a big impact. Surprise findings Tarisfirst trial involved implanting an empty device (with no drugs) inside volunteers to test comfort levels.
a nurse called and asked about every ache and pain, Cima says. After two weeks, there were none.
whom also had called lesions Hunner lesions, which affect about 10 to 15 percent of IC sufferers.
Usually, doctors cauterize these lesions (which don disappear on their own) while patients are under anesthesia in an operating room.
But the resulting scarring sometimes leads to patients losing some bladder function. uch to our surprise
in our trials, the lesions in those using Liris disappeared after two weeksin five out of six patients,
Results of both trials were published in 2012 in the journal Science Translational Medicine. Last year, Taris began an ongoing focus study specifically on patients with Hunner lesions.
ain is a subjective outcome, Cima says, ut the disappearance of the Hunner lesions was a purely objective outcome.
That objective result, I believe, is one important factor that Allegan decided to acquire the product.
Taris itself had also become a leading expert in interstitial cystitis. So that helped too. With the Allergan acquisition funds, Taris will further develop the device to deliver drugs for other bladder diseases,
including chemotherapy for bladder cancer whose high recurrence rate is due, in part, to difficulties delivering drugs in a sustained way.
Last year, Taris entered a research collaboration with Astrazeneca to develop novel treatments for bladder cancer. his device is a platform
Cima says. hether it bladder cancer, overactive or underactive bladder any of these indications where you might want to deliver drugs right to the bladder it can do that.
A member of the MIT Koch Institute, Cima is also working on other drug-delivery projects,
such as intraperitoneal chemotherapy delivery to treat ovarian cancer, funded in part by the Bridge Project
#Nanoparticles get a magnetic handle A long-sought goal of creating particles that can emit a colorful fluorescent glow in a biological environment
The new technology could make it possible to track the position of the nanoparticles as they move within the body or inside a cell.
At the same time the nanoparticles could be manipulated precisely by applying a magnetic field to pull them along. And finally the particles could have a coating of a bioreactive substance that could seek out
and bind with particular molecules within the body such as markers for tumor cells or other disease agents.
It s been a dream of mine for many years to have a nanomaterial that incorporates both fluorescence
and magnetism in a single compact object says Moungi Bawendi the Lester Wolfe Professor of Chemistry at MIT and senior author of the new paper.
Compactness is critical for biological and a lot of other applications. In addition previous efforts were unable to produce particles of uniform and predictable size
which could also be an essential property for diagnostic or therapeutic applications. Moreover Bawendi says We wanted to be able to manipulate these structures inside the cells with magnetic fields
but also know exactly what it is we re moving. All of these goals are achieved by the new nanoparticles
which can be identified with great precision by the wavelength of their fluorescent emissions. The new method produces the combination of desired properties in as small a package as possible Bawendi says which could help pave the way for particles with other useful properties such as the ability to bind with a specific type of bioreceptor or another
and postdoc Ou Chen the nanoparticles crystallize such that they self-assemble in exactly the way that leads to the most useful outcome:
That puts the fluorescent molecules in the most visible location for allowing the nanoparticles to be tracked optically through a microscope.
because the starting material fluorescent nanoparticles that Bawendi and his group have been perfecting for years are themselves perfectly uniform in size.
Initially at least the particles might be used to probe basic biological functions within cells Bawendi suggests.
As the work continues later experiments may add additional materials to the particles coating so that they interact in specific ways with molecules or structures within the cell either for diagnosis or treatment.
Watch how supernanoparticles are made to glow and manipulated with magnets inside a cancer cell. Video: Melanie Gonick/MIT The ability to manipulate the particles with electromagnets is key to using them in biological research Bawendi explains:
The tiny particles could otherwise get lost in the jumble of molecules circulating within a cell.
A silica coating on the particles allows additional molecules to attach causing the particles to bind with specific structures within the cell.
Silica makes it completely flexible; it s a well developed material that can bind to almost anything Bawendi says.
For example the coating could have a molecule that binds to a specific type of tumor cells;
so you could see the spatial macroscopic outlines of a tumor he says. The next step for the team is to test the new nanoparticles in a variety of biological settings.
We ve made the material Chen says. Now we ve got to use it and we re working with a number of groups around the world for a variety of applications.
Christopher Murray a professor of chemistry and materials science and engineering at the University of Pennsylvania who was connected not with this research says This work exemplifies the power of using nanocrystals as building blocks for multiscale and multifunctional structures.
We often use the term artificial atoms in the community to describe how we are exploiting a new periodic table of fundamental building blocks to design materials
Massachusetts General Hospital; Institut Curie in Paris; the Heinrich-Pette Institute and the Bernhard-Nocht Institute for Tropical Medicine in Hamburg Germany;
Children s Hospital Boston; and Cornell University. The work was supported by the National institutes of health the Army Research Office through MIT s Institute for Soldier Nanotechnologies and the Department of energy y
#Untangling how cables coil The world fiber-optic network spans more than 550,000 miles of undersea cable that transmits e-mail, websites,
and other packets of data between continents, all at the speed of light. A rip or tangle in any part of this network can significantly slow telecommunications around the world.
Now engineers at MIT, along with computer scientists at Columbia University, have developed a method that predicts the pattern of coils
and tangles that a cable may form when deployed onto a rigid surface. The research combined laboratory experiments with custom-designed cables
computer-graphics technology used to animate hair in movies, and theoretical analyses. In the lab, MIT engineers set up a desktop system to spool spaghetti-like cables onto a conveyor belt.
They adjusted parameters such as speed of deployment and the speed of the belt, and observed how the cable coiled as it hit the surface.
At Columbia, computer scientists adapted a source code used for simulating animated hair and, incorporating the parameters of the MIT experiment,
and data loss. e now have a set of design guidelines that allow you to tune certain parameters to achieve a particular pattern,
an associate professor of mechanical engineering and civil and environmental engineering at MIT. e have a description that applies to many systems.
and Eitan Grinspun of Columbia University. Shipping up to Boston Fiber-optic cables are deployed typically from a sailing vessel,
then the cable can get taut and fracture, which is really bad news . So we wanted to understand what was underlying those patterns.
and his students fabricated filaments from silicone-based rubber, and rigged a spool to automatically reel out the wire onto a conveyor belt.
The team used a digital video camera to record the filamentsmotion as they hit the belt,
Reis teamed up with Grinspun, an expert in discrete differential geometry. Grinspun has applied sophisticated mathematical methods to simulating the movement of thin filaments such as hair
so a lot of algorithms we develop, we need to think about geometry. Grinspun had upgraded previously a code he developed to simulate hair to model the flow of viscous fluids like honey.
As honey is poured from a jar, it can resemble rope or thread, drizzling onto a surface in wavelike patterns.
so we thought that we should port some of his algorithms into engineering, and test if these patterns can be predicted,
which, when wound on a spool, retains a certain amount of curve as it unwound.
For example, an understanding of such relationships from an engineering standpoint may improve the animation of phenomena such as hair blowing in the wind. think what we now have is a bridge between these two fields,
#Fast cheap nanomanufacturing Luis Fernando Velsquez-Garc a s group at MIT s Microsystems Technology Laboratories (MTL) develops dense arrays of microscopic cones that harness
depositing or etching features onto nanoscale mechanical devices; spinning out nanofibers for use in water filters body armor and smart textiles;
or propulsion systems for fist-sized nanosatellites. In the latest issue of the IEEE Journal of Microelectromechanical systems Velsquez-Garc a his graduate students Eric Heubel and Philip Ponce de Leon and Frances Hill a postdoc in his group describe a new prototype
array that generates 10 times the ion current per emitter that previous arrays did. Ion current is a measure of the charge carried by moving ions
The same prototype also crams 1900 emitters onto a chip that s only a centimeter square quadrupling the array size and emitter density of even the best of its predecessors.
because scaling down emitters implies less power consumption less bias voltage to operate them and higher throughput says Velsquez-Garca a principal research scientist at MTL.
Surface tension wicks the fluid up the side of the emitters to the tip of the cone whose narrowness concentrates the electrostatic field.
But in the new work they instead used carbon nanotubes atom-thick sheets of carbon rolled into cylinders grown on the slopes of the emitters like trees on a mountainside.
and height of the nanotubes the researchers were able to achieve a fluid flow that enabled an operating ion current at very near the theoretical limit.
We also show that they work uniformly that each emitter is doing exactly the same thing Velsquez-Garc a says.
That s crucial for nanofabrication applications in which the depth of an etch or the height of deposits must be consistent across an entire chip.
To control the nanotubes growth the researchers first cover the emitter array with an ultrathin catalyst film
which is broken into particles by chemical reactions with both the substrate and the environment. Then they expose the array to a plasma rich in carbon.
The nanotubes grow up under the catalyst particles which sit atop them until the catalyst degrades.
Increasing the emitter density the other improvement reported in the new paper was a matter of optimizing existing manufacturing recipe Velsquez-Garca says.
The emitters like most nanoscale silicon devices were produced through photolithography a process in which patterns are transferred optically to layers of materials deposited on silicon wafers;
a plasma then etches the material away according to the pattern. The recipe is the gases power pressure level time
and the sequence of the etching Velsquez-Garca says. We started doing electrospray arrays 15 years ago
Nanoprintingvelsquez-Garca believes that using arrays of emitters to produce nanodevices could have several advantages over photolithography the technique that produces the arrays themselves.
and don t require a vacuum chamber the arrays could deposit materials that can t withstand the extreme conditions of many micro-and nanomanufacturing processes.
In my opinion the best nanosystems are going to be done by 3-D printing because it would bypass the problems of standard microfabrication Velsquez-Garca says.
which requires a high level of training to operate and everything is defined in planes. In many applications you want the three-dimensionality:
3-D printing is going to make a big difference in the kinds of systems we can put together
and not a beam of droplets says Herbert Shea an associate professor in the Microsystems for Space technologies Laboratory at the cole Polytechnique F d rale de Lausanne.
Using their nanotube forest they re able to get the devices to operate in pure ion mode
However large concentrations of ethanol can be toxic to yeast which has limited the production capacity of many yeast strains used in industry.
Toxicity is probably the single most important problem in cost-effective biofuels production says Gregory Stephanopoulos the Willard Henry Dow Professor of Chemical engineering at MIT.
Now Stephanopoulos and colleagues at MIT and the Whitehead Institute for Biomedical Research have identified a new way to boost yeast tolerance to ethanol by simply altering the composition of the medium in
They also showed that this approach works with commercial yeast strains and other types of alcohols including propanol and butanol
which are even more toxic to yeast. The more we understand about why a molecule is toxic
and methods that will make these organisms more tolerant the more people will get ideas about how to attack other more severe problems of toxicity says Stephanopoulos one of the senior authors of the Science paper.
This work goes a long way to squeezing the last drop of ethanol from sugar adds Gerald Fink an MIT professor of biology member of the Whitehead Institute and the paper s other senior author.
Postdoc Felix Lam is the paper s lead author and graduate student Adel Ghaderi also contributed to the study.
Reinforcing cell defensesthe research team began this project searching for a gene or group of genes that could be manipulated to make yeast more tolerant to ethanol
By augmenting the yeast s environment with potassium chloride and increasing the ph with potassium hydroxide the researchers were able to dramatically boost ethanol production.
They also found that these changes did not affect the biochemical pathway used by the yeast to produce ethanol:
which produce energy that the cell can harness to control the flow of various molecules into and out of the cell.
Industrial relevancebefore yeast begin their work producing ethanol the starting material usually corn must be broken down into glucose.
Lonnie Ingram director of the Florida Center for Renewable Chemicals and Fuels at the University of Florida describes the MIT team s discovery as remarkable and unexpected.
They are also working on using this approach to boost the ethanol yield from various industrial feedstocks that because of starting compounds inherently toxic to yeast now have low yields.
The research was funded by the MIT Energy Initiative and the Department of energy y
#MIT launches Laboratory for Social Machines with major Twitter investment The MIT Media Lab today announced the creation of the Laboratory for Social Machines (LSM), funded by a five-year, $10 million
commitment from Twitter. As part of the new program, Twitter will also provide full access to its real-time, public stream of tweets,
as well as the archive of every tweet dating back to the first. The new initiative, based at the Media Lab, will focus on the development of new technologies to make sense of semantic and social patterns across the broad span of public mass media
social media, data streams, and digital content. Pattern discovery and data visualization will be explored to reveal interaction patterns and shared interests in relevant social systems,
while collaborative tools and mobile apps will be developed to enable new forms of public communication and social organization.
A main goal for the LSM will be to create new platforms for both individuals and institutions to identify,
Though funded by Twitter, the LSM will have complete operational and academic independence. In keeping with the academic mission of LSM, students and staff will work across many social media
and mass media platforms including, but not limited to, Twitter. he Laboratory for Social Machines will experiment in areas of public communication
and social organization where humans and machines collaborate on problems that can be solved manually or through automation alone, says Deb Roy,
an associate professor at the Media Lab who will lead the LSM, and who also serves as Twitter chief media scientist."
"Social feedback loops based on analysis of public media and data can be an effective catalyst for increasing accountability
and transparency creating mutual visibility among institutions and individuals.""""With this investment, Twitter is seizing the opportunity to go deeper into research to understand the role Twitter
and other platforms play in the way people communicate, the effect that rapid and fluid communication can have
"says Dick Costolo, CEO of Twitter.""As social media leads us into the emergence of a new era of communication and engagement, the LSM,
in collaboration with Twitter, will create analytical tools to help turn the vision of a new public sphere into reality,
"adds Joi Ito, director of the MIT Media Lab T
#High-speed biologics screen MIT engineers have devised a way to rapidly test hundreds of different drug-delivery vehicles in living animals making it easier to discover promising new ways to deliver a class of drugs called biologics
which includes antibodies peptides RNA and DNA to human patients. In a study appearing in the journal Integrative biology the researchers used this technology to identify materials that can efficiently deliver RNA to zebrafish and also to rodents.
This type of high-speed screen could help overcome one of the major bottlenecks in developing disease treatments based on biologics:
It is challenging to find safe and effective ways to deliver them. Biologics is the fastest growing field in biotech
because it gives you the ability to do highly predictive designs with unique targeting capabilities says senior author Mehmet Fatih Yanik an associate professor of electrical engineering and computer science and biological engineering.
However delivery of biologics to diseased tissues is challenging because they are significantly larger and more complex than conventional drugs.
By combining this work with our previously published high-throughput screening system we are able to create a drug-discovery pipeline with efficiency we had imagined never before adds Tsung-Yao Chang a recent MIT Phd recipient and one of the paper s lead authors.
Peng Shi a former MIT postdoc who is now an assistant professor at the University of Hong kong is the paper s other lead author.#
#Fish on the flyzebrafish are used commonly to model human diseases in part because their larvae are transparent making it easy to see the effects of genetic mutations or drugs.#
#In 2010 Yanik s team developed a technology for rapidly moving zebrafish larvae to an imaging platform orienting them correctly
and imaging them. This kind of automated system makes it possible to do large-scale studies because analyzing each larva takes less than 20 seconds compared with the several minutes it would take for a scientist to evaluate the larvae by hand.
For this study Yanik s team developed a new technology to inject RNA carried by nanoparticles called lipidoids previously designed by Daniel Anderson an associate professor of chemical engineering member of the Koch Institute for Integrative Cancer Research and Institute
for Medical Engineering and Science and an author of the new paper. These fatty molecules have shown promise as delivery vehicles for RNA interference a process that allows disease-causing genes to be turned off with small strands of RNA.#
#Yanik s group tested about 100 lipidoids that had performed not well in tests of RNA delivery in cells grown in a lab dish.
They designed each lipidoid to carry RNA expressing a fluorescent protein allowing them to easily track RNA delivery
Then the lipidoid-RNA complex was injected automatically guided by a computer vision algorithm. The system can be adapted to target any organ
#A few hours after injection the researchers imaged the zebrafish to see if they displayed any fluorescent protein in the brain indicating
#The ability to identify useful drug delivery nanoparticles using this miniaturized system holds great potential for accelerating our discovery process Anderson says.
The lipidoid material screen is just an example demonstrated in this article; a similar strategy can be extended readily to other libraries
#Jeff Karp an associate professor of medicine at Harvard Medical school who was not part of the research team says this work is an excellent example of harnessing a multidisciplinary team to partner complementary technologies for the purpose of solving a unified problem.
and other small animals have teamed up with Anderson et al. who are leading experts in RNA delivery to create a new platform for rapidly screening biologics
This approach should have utility across multiple disease areas. New leadsthe researchers are now using
If we can pick up certain design features from the screens it can guide us to design larger combinatorial libraries based on these leads Yanik says.
Yanik s lab is currently using this technology to find delivery vehicles that can carry biologics across the blood-brain barrier a very selective barrier that makes it difficult for drugs
but not much of the rest of the spectrum since that would increase the energy that is reradiated by the material
The material is a two-dimensional metallic dielectric photonic crystal and has the additional benefits of absorbing sunlight from a wide range of angles
The creation of this material is described in a paper published in the journal Advanced Materials co-authored by MIT postdoc Jeffrey Chou professors Marin Soljacic Nicholas Fang Evelyn Wang and Sang-Gook
The material works as part of a solar-thermophotovoltaic (STPV) device: The sunlight s energy is converted first to heat
which then causes the material to glow emitting light that can in turn be converted to an electric current.
Some members of the team worked on an earlier STPV device that took the form of hollow cavities explains Chou of MIT s Department of Mechanical engineering who is the paper s lead author.
No one had tried putting a dielectric material inside so we tried that and saw some interesting properties.
It s a very specific window that you want to absorb in he says. We built this structure
Earlier lab demonstrations of similar systems could only produce devices a few centimeters on a side with expensive metal substrates so were not suitable for scaling up to commercial production he says.
which would add greatly to the complexity and expense of a solar power system. This is the first device that is able to do all these things at the same time Chou says.
While the team has demonstrated working devices using a formulation that includes a relatively expensive metal ruthenium we re very flexible about materials Chou says.
In theory you could use any metal that can survive these high temperatures. This work shows the potential of both photonic engineering
and materials science to advance solar energy harvesting says Paul Braun a professor of materials science and engineering at the University of Illinois at Urbana-Champaign who was involved not in this research.
In this paper the authors demonstrated in a system designed to withstand high temperatures the engineering of the optical properties of a potential solar thermophotovoltaic absorber to match the sun s spectrum.
Of course much work remains to realize a practical solar cell however the work here is one of the most important steps in that process.
The group is now working to optimize the system with alternative metals. Chou expects the system could be developed into a commercially viable product within five years.
He is working with Kim on applications from this project. The team also included MIT research scientist Ivan Celanovic and former graduate students Yi Yeng Yoonkyung Lee Andrej Lenert and Veronika Rinnerbauer.
The work was supported by the Solid-state Solar Thermal energy Conversion Center and the U s. Department of energy y
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011