Posts Tagged ‘MIT’

DARPA (US Defense Advanced Research Projects Agency), nanoparticles, and your traumatized brain

Friday, May 10th, 2013

According to the May 10, 2013 news item on Nanowerk,

DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections.

Led by Professor Michael J. Sailor, Ph.D., from the University of California San Diego [UC San Diego], the award brings together a multi-disciplinary team of renowned experts in laboratory research, translational investigation and clinical medicine, including Erkki Ruoslahti, M.D., Ph.D. of Sanford-Burnham Medical Research Institute, Sangeeta N. Bhatia, M.D., Ph.D. of Massachusetts Institute of Technology and Clark C. Chen, M.D., Ph.D. of UC San Diego School of Medicine.

Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.

“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said Chen, a neurosurgeon with UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.

The May 9, 2013 UC San Diego news release by Susan Brown, which originated the news item, describes the reasons why DARPA wants to use nanoparticles in therapies for people suffering from traumatic brain injury,

Under normal conditions, the brain is protected from infection by a physiological system called the blood-brain barrier. “Unfortunately, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold,” said Chen, associate professor and vice-chair of research in the Division of Neurosurgery at UC San Diego School of Medicine.

DARPA hopes to meet these challenges with nanotechnology. The agency awarded this grant under its In Vivo Nanoplatforms for Therapeutics program to construct nanoparticles that can find and treat infections and other damage associated with traumatic brain injuries.

“Our approach is focused on porous nanoparticles that contain highly effective therapeutics on the inside and targeting molecules on the outside,” said Sailor, the UC San Diego materials chemist who leads the team. “When injected into the blood stream, we have found that these silicon-based particles can target certain tissues very effectively.”

Several types of nanoparticles have already been approved for clinical use in patients, but none for treatment of trauma or diseases in the brain. This is due in part to the inability of nanoparticle formulations to cross the blood-brain barrier and reach their intended targets.

“Poor penetration into tissues limits the application of nanoparticles to the treatment of many types of diseases,” said Ruoslahti, distinguished professor at Sanford-Burnham and partner in the research. “We are trying to overcome this limitation using targeting molecules that activate tissue-specific transport pathways to deliver nanoparticles.”

There is another major hurdle for treating brain injuries (from the news release),

Treating brain infections is becoming more difficult as drug-resistant strains of viruses and bacteria have emerged. Because drug-resistant strains mutate and evolve rapidly, researchers must constantly adjust their approach to treatment.

In an attempt to hit this moving target, the team is making their systems modular, so they can be reconfigured “on-the-fly” with the latest therapeutic advances.

Nanocomplexes that contain genetic material known as short interfering RNA, or siRNA, developed by Bhatia’s research group at MIT, will be key to this aspect of the team’s approach.

“The function of this type of RNA is that it specifically intereferes with processes in a diseased cell. The advantage of RNA therapies are that they can be quickly and easily modified when a new disease target emerges,” said Bhatia, a bioengineering professor at MIT and partner in the research.

But effective delivery of siRNA-based therapeutics in the body has proven to be a challenge because the negative charge and chemical structure of naked siRNA makes it very unstable in the body and it has difficulty crossing into diseased cells. To solve these problems, Bhatia has developed nanoparticles that form a protective coating around siRNA.

“The nanocomplexes we are developing shield the negative charge of RNA and protect it from nucleases that would normally destroy it. Adding Erkki’s tissue homing and cell-penetrating peptides allows the nanocomplex to transport deep into tissue and enter the diseased cells,” she said.

Bhatia has previously used the cell-penetrating nanocomplex to deliver siRNA to a tumor cell and shut down its protein production machinery. Although her group’s effort has focused on cancer, the team is now going after two other hard-to-treat cell types: drug-resistant bacteria and inflammatory cells in the brain.

“The work proposed by this multi-disciplinary team should provide new tools to mitigate the debilitating effects of penetrating brain injuries and offer our warfighters the best chance of meaningful recovery,” Chen said. [emphasis mine]

BTW, the term ‘warfighters’ is new to me; are we replacing the word ‘soldier’?

Returning to the matter at hand, I found DARPA’s In Vivo Nanoplatforms for Therapeutics program which is described this way on its home page,

Disease limits soldier readiness and creates healthcare costs and logistics burdens. Diagnosing and treating disease faster can help limit its impact. [emphasis mine] Current technologies and products for diagnosing disease are principally relegated to in vitro (in the lab) medical devices, which are often expensive, bulky and fragile.

DARPA’s In Vivo Nanoplatforms (IVN) program seeks to develop new classes of adaptable nanoparticles for persistent, distributed, unobtrusive physiologic and environmental sensing as well as the treatment of physiologic abnormalities, illness and infectious disease.

The IVN Diagnostics (IVN:Dx) program effort aims to develop a generalized in vivo platform that provides continuous physiological monitoring for the warfighter. [emphasis mine] Specifically, IVN:Dx will investigate technologies that may provide:

  • Implantable nanoplatforms using bio-compatible and nontoxic materials
  • In vivo sensing of small and large molecules of biological interest
  • Multiplexed detection of analytes at clinically relevant concentrations
  • External interrogation of the nanoplatform free from any implanted communications electronics
  • Complete system demonstration in a large animal

The IVN Therapeutics (IVN:Tx) program effort will seek unobtrusive nanoplatforms for rapidly treating disease in warfighters.

(I see DARPA is using both soldier and warfighter’.)

This team is not the only one wishing to deliver drug therapies in a targeted fashion to the brain. My Feb. 19, 2013 posting mentioned Chad Mirkin (Northwestern University) and his team’s efforts with spherical nucleic acids (SNAs), from the posting,

Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine. (originally excerpted from this the Feb. 15, 2013 news release on EurekAlert)

Coincidentally, Mirkin has just been named ‘Chemistry World Entrepreneur of the Year’ by the UK’s Royal Society of Chemistry, from the May 10, 2013 news item on Nanowerk,

Northwestern University scientist Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has been named 2013 Chemistry World Entrepreneur of the Year by the Royal Society of Chemistry (RSC). The award recognizes an individual’s contribution to the commercialization of research.

The RSC is honoring Mirkin for his invention of spherical nucleic acids (SNAs), new globular forms of DNA and RNA. These structures form the basis for more than 300 products commercialized by licensees of the technology.

I’m never quite sure what to make of researchers who receive public funding then patent and license the results of that research.

Getting back to soldiers/warfighters, I’m glad to see this research being pursued. Years ago, a physician mentioned to me that soldiers in Iraq were surviving injuries that would have killed them in previous conflicts. The problem is that the same protective gear which insulates soldiers against many injuries makes them vulnerable to abusive head trauma (same principle as ‘shaken baby syndrome’). For example, imagine having a high velocity bullet hit your helmet. You’re protected from the bullet but the impact shakes your head so violently, your brain is injured.

EmTech México 2013

Thursday, May 9th, 2013

MIT (Massachusetts Institute of Technology) produces an annual emerging technologies conference (EmTech) on its own home ground of Cambridge, MA and also in India (mentioned in my Mar. 5, 2010 posting; scroll down 2/3 of the way), in China, in Spain (mentioned in my Oct. 28, 2011 posting; scroll down about 1/4 of the way) and, of particular interest to me, in México.

The ‘nanotechnology’ bombings in México in 2011 and in early 2013, mentioned most recently in my Mar. 14, 2013 posting, provide an interesting backdrop to the upcoming conference (EmTech México 29-30 mayo, 2013 • Ciudad de México).

The speaker list for the conference is, as expected, heavy with MIT faculty but it also boasts someone I’ve featured here from time to time, Tim Harper of Cientifica. Here’s the description they have for Tim (from the EmTech México speaker [biography] page),

Tim Harper es uno de los principales expertos en la comercialización de nanotecnología y de tecnologías emergentes. Le interesan además la biología sintética, la medicina regenerativa y la geoingeniería.

Harper es un emprendedor, inversor en tecnologías emergentes y asesor gubernamental en materia de estrategia tecnológica. Es fundador y CEO de Cientifica, la empresa más respetada a nivel mundial en materia de información nanotecnológica y pronósticos meteorológicos. Harper fue cofundador de la empresa Nanosight, donde desarrolló un innovador sistema de detección de nanopartículas.

Perteneció al  equipo de  ingenieros de la Agencia Espacial Europea en el centro de I+D en Norrdwijk (Países Bajos). Allí contribuyó decisivamente al lanzamiento del primer microscopio de fuerza atómica en el espacio, donde nunca se había analizado el polvo cósmico.

En 1999, Harper organizó en Sevilla (España) la primera conferencia del mundo sobre inversión en nanotecnología. Desde entonces dirige con éxito el World Nanoeconomic Congress en cuatro continentes. En el año 2002 fundó la European NanoBusiness Association, una sociedad sin ánimo de lucro cuyo objetivo es promover la competitividad europea en materia de nanotecnología.

I gather the conference will be held  in Spanish. My skills in this language are almost nonexistent but relying heavily on my poor French, here’s a rough translation of the first paragraph,

Tim Harper is an expert on the commercialization of nanotechnology and other emerging technologies. He also maintains a professional interest in the fields of synthetic biology, regenerative medicine, and geoengineering.

Here are a few of the other speakers listed on the EmTech México conference’s Ponentes page,

  • Jason Pontin, Director de MIT Technology Review
  • Mario Molina, Premio Nobel de Química (1995)
  • Niels Van Duinen, Director de Desarrollo de Negocio Internacional de Philips Lighting
  • Carlo Ratti, Director del grupo Senseable City Lab en el MIT
  • Marcelo Coelho, Diseñador e investigador del grupo Fluid Interfaces en el MIT Media Lab
  • Juan Pablo Puerta, Director de Ingenería, Etsy
  • Marisa Viveros, Vicepresidenta de Cyber Security Innovation de IBM

You can check out all of the Emtech conferences on this page.

One last note, MIT has its own baggage viz the recent suicide of Aaron Swartz. This essay on Wikipedia offers one of the more neutral descriptions. I’ve excerpted the introduction, (Note: Links and footnotes have been removed),

Aaron Hillel Swartz (November 8, 1986 – January 11, 2013) was an American computer programmer, writer, political organizer and Internet activist.

Swartz was involved in the development of the web feed format RSS,[ the organization Creative Commons,] the website framework web.py and the social news site Reddit, in which he was an equal partner after its merger with his Infogami company. Swartz also focused on sociology, civic awareness and activism. In 2010, he became a research fellow at Harvard University’s Edmond J. Safra Research Lab on Institutional Corruption, directed by Lawrence Lessig. He founded the online group Demand Progress, known for its campaign against the Stop Online Piracy Act.

On January 6, 2011, Swartz was arrested by MIT police on state breaking-and-entering charges, in connection with the systematic downloading of academic journal articles from JSTOR. Federal prosecutors eventually charged him with two counts of wire fraud and 11 violations of the Computer Fraud and Abuse Act, charges carrying a cumulative maximum penalty of $1 million in fines plus 35 years in prison, asset forfeiture, restitution and supervised release.

On January 11, 2013, two years after his initial arrest, Swartz was found dead in his Crown Heights, Brooklyn apartment, where he had hanged himself.

MIT president L. Rafael Reif has since ordered a review of MIT’s role in the tragedy noted in the Wikipedia essay and elsewhere. The essay on Aaron Swartz offers a fairly comprehensive overview of Swartz’s life and accomplishments, as well as, his legal situation and the circumstances surrounding his death.

A suicide is a complex event and it is not possible to hold any one person or institution to blame, tempting as it may be. Nonetheless, it must be said that it seems oddly dissonant that MIT which prides itself on its technological advancements  and membership in an elite, forward-thinking research community would be party to an action where prosecutors seemed more intent on punishment than on any principle of law relating to research and its dissemination. Whatever one thinks of Swartz’s actions, it is clear he was acting out of a spirit of civil disobedience (trying to set publicly funded research free).

In fact, the emerging technologies of yesteryear are have social impacts today such that the ways in which we view research and the scientific process are changing prompting questions such as ‘Who gets access to information and ideas?’ and, as  importantly, ‘When?’

I wonder if any of these events, the multiple bombings in México and MIT’s role in the Swartz case and suicide will have any sort of impact on this conference. I doubt it; there wasn’t a single philosopher on the speaker’s list.

Jason Pontin

Director de MIT Technology Review

Emory University’s Shuming Nie discusses Iron Man 3 and nanotechnology and researchers develop an injectable nano-network

Monday, May 6th, 2013

I have written about Iron Man 3 before (my May 11, 2012 posting) in the context of its nanotechnology inspirations, specifically, the Extremis Armor. For anyone not familiar with the story, I have a few bits which will bring you up to speed before getting to Shuming Nie’s commentary and some recent research into injectable nano-networks, which seems highly relevant to the Iron Man 3 discourse. First, here’s an excerpt from my May 11, 2012 posting,

In a search for Extremis, I found out that this story reboots the Iron Man mythology by incorporating nanotechnology and alchemy to create a new armor, the Extremis Armor, from the Extremis Armor website (I strongly suggest going to the website and reading the full text which includes a number of illustrative images if you find this sort of thing interesting),

When a bio-tech weapon of mass destruction was unleashed, Tony Stark threw himself onto the bleeding edge between science and alchemy, combining nanotechnology and his Iron Man armor.  The result, which debuted in Iron Man, Vol. IV, issue 5, was the Extremis Armor, Model XXXII, Mark I, which made him the most powerful hero in the world–but not without a price.

There were two key parts to this Extremis-enhanced suit.  The first part is the golden Undersheath, the protective interface between Stark’s nervous system and the second chief part, the External Suit Devices (ESDs), a.k.a. the red armor plating.

The Undersheath to the Iron Man suit components was super-compressed and stored in the hollows of Stark’s bones. The sheath material exited through skeletal pores and slid between all cells to self-assemble a new “skin” around him.  This skin provides a complete interface to the Iron Man suit components and can perform numerous other functions. (The process in reverse withdrew the Undersheath back into these specially modified areas of Tony Stark’s bone marrow tissue.)

The Undersheath is a nano-network that incorporates peptide-peptide logic (PPL), a molecular computational system made of superconducting plastic impregnated molecular chains. [my emphasis added for May.6.13 posting]  The PPL handles, among other things: memory, critical logic paths, comparative “truth” tables, automatic response look-up tables, data storage, communication, and external sensing material interface.

The lattice assembly is a stress-compression truss with powered interstitial joints.  This can surround the PPL material and guide it through Stark’s body.  This steerable, motile lattice framework is commanded by the PPL molecule computational mentality.  The metallic component to the lattice is a controlled mimetic artifact that can take on the characteristics of most elements.  Even unusual combinations of behaviors such as extreme hardness and flexibility.

The combination of the two nano-scale materials allows for a very dense non-traditional computer that can change the fabric of its design in very powerful ways. The incorporation of the Undersheath in Stark’s entire nervous system renders reflex-level computer responses to pan-spectrum stimuli.

Anthony Stark’s Bio/Metalo-Mimetic Material concept is a radical departure from the traditional solid-state underpinnings of his prior Iron Man suit designs.  Making use of nano-scale assembly technology, “smart” molecules can be made atom by atom. The design allows for simple computers to be linked into a massive parallel computer that synthesizes human thought protocols.

The External Suit Devices (ESDs), the red armor plates, were made via mega-nano technology that has assembled atoms into large, discreet effectors.  This allows for the plates to be collapsable to very small volumes for easy storage and carried in Stark’s briefcase. The ESDs were commanded by the Undersheath and were self-powered by high-capacity Kasimer plates.  They were equipped with large arrays of nano-fans that allow flight.  Armoring-up was done by drawing the suit to Stark via a vectored repulsor field, just lightly pushing them from different angles.

The armor’s memory-metal technology renders it lightweight and flexible while not in use, but extremely durable when polarized.  The armor was strong, of course, but it could be made even stronger by rerouting repulsor input to reinforce the armor’s mass.

Stark’s skin is now a part of the suit, when engaged.  [emphasis mine] Comfort is relative because the suit rapidly responds to any discomfort, from impacts to high temperatures, from itching to scratching.  The suit’s protocols include semi-autonomy when needed.  Where Stark ends and the suit begins is flexible.  The exact nature of the artificial Extremis Virus is not known (especially because Stark recompiled the dose, then tweaked the nutrients and suspended metals, radically altering Maya Hansen’s [the character Rebecca Hall will reputedly play] formulations).  The effect it has had on Stark’s body is to allow the presence of so much alien material within his body without trauma.

Because of the bio-interface between Tony and the armor, he could utilize the suit to its fullest potential and also instantly access computers and any digital system worldwide at the speed of thought.  He was biologically integrated with his armor, one with it, imbued with unprecedented powers and abilities.  He channeled and processed data, emergency signals, and satellite reconnaissance from every law enforcement, military, and intelligence service in the world–in his head.  He could send electronic signals and make phone calls with his mind.  He could see through satellites.  Plus he had the ability to transmit whatever he saw (from his visual cortex) to other people’s display screens.  The computer’s cybernetic link enables him to operate all of the armor’s functions, as well as providing a remote link to other computers (as Stark is now part of the armor this connection is seamless).  The armor’s system was connected to the global mainframe via StarkTech servers.

I also like this more generalized description of the technology in the Wikipedia essay on Extemis Comics (Note: A link has been removed),

Extremis has been referred to as a “virus” constantly since the story. The verbatim description offered by its inventor Maya Hansen, goes: “…Extremis is a super-soldier solution. It’s a bio-electronics package, fitted into a few billion graphite nanotubes and suspended in a carrier fluid. [emphasis mine] A magic bullet, like the original super-soldier serum—all fitted into a single injection. It hacks the body’s repair center—the part of the brain that keeps a complete blue print of the human body. When we’re injured, we refer to that area of the brain to heal properly. Extremis rewrites the repair center. In the first stage, the body essentially becomes an open wound. The normal human blueprint is being replaced with the Extremis blueprint. The brain is being told the body is wrong. Extremis protocol dictates that the subject be placed on life support and intravenously fed nutrients at this point. For the next two or three days, the patient remains unconscious within a cocoon of scabs. (…) Extremis uses the nutrients and body mass to grow new organs. Better ones…”

A Postmedia movie reviewer, Katherine Monk noted this about the plot in her May 3, 2013 review of Iron Man 3 ,

Apparently, back in the early days of genetic engineering, a brilliant, zit-faced scientist (Guy Pearce) offered Tony a piece of a lucrative patent that had the potential to alter the human body, and even regenerate amputated limbs.

Tony walked away from the offer as well as the pretty girl (Rebecca Hall) who worked for the genetic engineer, but in the opening sequence, we see the technology was successfully developed and tested. It makes people superhuman, but it can also make them spontaneously combust, leaving great craters and human casualties behind.

Now for the video commentary, Dr. Shuming Nie, Biomedical Engineering at Emory University, offers some scientific insight into the science and the fiction of ‘extremis’ as per Iron Man 3 in his YouTube video,

Keeping on the science theme,  researchers at North Carolina State University (NCSU) and other institutions announced an injectable nano-network for diabetics in a May 3, 2013 news release on EurekAlert,

In a promising development for diabetes treatment, researchers have developed a network of nanoscale particles that can be injected into the body and release insulin when blood-sugar levels rise, maintaining normal blood sugar levels for more than a week in animal-based laboratory tests. The work was done by researchers at North Carolina State University, the University of North Carolina at Chapel Hill, the Massachusetts Institute of Technology and Children’s Hospital Boston.

“We’ve created a ‘smart’ system that is injected into the body and responds to changes in blood sugar by releasing insulin, effectively controlling blood-sugar levels,” says Dr. Zhen Gu, lead author of a paper describing the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill. “We’ve tested the technology in mice, and one injection was able to maintain blood sugar levels in the normal range for up to 10 days.”

Here’s how the smart system is achieved,

The new, injectable nano-network is composed of a mixture containing nanoparticles with a solid core of insulin, modified dextran and glucose oxidase enzymes. When the enzymes are exposed to high glucose levels they effectively convert glucose into gluconic acid, which breaks down the modified dextran and releases the insulin. The insulin then brings the glucose levels under control. The gluconic acid and dextran are fully biocompatible and dissolve in the body.

Each of these nanoparticle cores is given either a positively charged or negatively charged biocompatible coating. The positively charged coatings are made of chitosan (a material normally found in shrimp shells), while the negatively charged coatings are made of alginate (a material normally found in seaweed).

When the solution of coated nanoparticles is mixed together, the positively and negatively charged coatings are attracted to each other to form a “nano-network.” Once injected into the subcutaneous layer of the skin, the nano-network holds the nanoparticles together and prevents them from dispersing throughout the body. Both the nano-network and the coatings are porous, allowing blood – and blood sugar – to reach the nanoparticle cores.

“This technology effectively creates a ‘closed-loop’ system that mimics the activity of the pancreas in a healthy patient, releasing insulin in response to glucose level changes,” Gu says. “This has the potential to improve the health and quality of life of diabetes patients.”

For anyone who’s interested in researching further, heres’ a citation for and a link to the paper,

Injectable Nano-Network for Glucose-Mediated Insulin Delivery by Zhen Gu, Alex A. Aimetti, Qun Wang, Tram T. Dang, Yunlong Zhang, Omid Veiseh, Hao Cheng, Robert S. Langer, and Daniel G. Anderson. ACS Nano, Article ASAP DOI: 10.1021/nn400630x Publication Date (Web): May 2, 2013

Copyright © 2013 American Chemical Society

The paper is behind a paywall. Meanwhile, there are discussions about moving these injectable nano-networks into human clinical trials. As Nie notes, Iron Man 3 hints at new medical technologies which will be achievable in the next 10 or so years, although we may have to wait 100 to 150 years for  Extremis armor.

Beginner’s guide to carbon nanotubes and nanowires

Thursday, April 11th, 2013

There’s a very nice Apr. 11, 2013  introductory article by David L. Chandler for the Massachusetts Institute of Technology (MIT) news office) about carbon and other nanotubes and nanowires,

The initial discovery of carbon nanotubes — tiny tubes of pure carbon, essentially sheets of graphene rolled up unto a cylinder — is generally credited to a paper published in 1991 by the Japanese physicist Sumio Ijima (although some forms of carbon nanotubes had been observed earlier). Almost immediately, there was an explosion of interest in this exotic form of a commonplace material. Nanowires — solid crystalline fibers, rather than hollow tubes — gained similar prominence a few years later.

Due to their extreme slenderness, both nanotubes and nanowires are essentially one-dimensional. “They are quasi-one-dimensional materials,” says MIT associate professor of materials science and engineering Silvija Gradečak: “Two of their dimensions are on the nanometer scale.” This one-dimensionality confers distinctive electrical and optical properties.

For one thing, it means that the electrons and photons within these nanowires experience “quantum confinement effects,” Gradečak says. And yet, unlike other materials that produce such quantum effects, such as quantum dots, nanowires’ length makes it possible for them to connect with other macroscopic devices and the outside world.

The structure of a nanowire is so simple that there’s no room for defects, and electrons pass through unimpeded, Gradečak explains. This sidesteps a major problem with typical crystalline semiconductors, such as those made from a wafer of silicon: There are always defects in those structures, and those defects interfere with the passage of electrons.

H/T Nanowerk Apr. 11, 2013 news item. There’s more to read at the MIT website and I recommend this as a good beginner’s piece since the focus is entirely on what carbon nanotubes and nanowires are , how they are formed, and which distinctive properties are theirs. You can find some of this information in the odd paragraph of a news release touting the latest research but I’m very excited to find this much explanatory material in one place.

Another very good explanatory piece, this one focused on carbon nanotubes and risk, is a video produced by Dr. Andrew Maynard for his Risk Bites series. I featured and embedded it in my Mar. 15, 2013 posting. titled, The long, the short, the straight, and the curved of them: all about carbon nanotubes.  You can also find the video in Andrew’s Mar. 14, 2013 posting on his 2020 Science blog where he also writes about the then recently released information from the US National Institute of Occupational Health and Safety on carbon nanotubes and toxicity.

Inflammation isn’t all bad but sometimes you need to reduce it with nanomedicines

Tuesday, March 19th, 2013

Researchers from Brigham and Women’s Hospital (BWH), Columbia University Medical Center, Icahn School of Medicine at Mount Sinai, and Massachusetts Institute of Technology (MIT) have published about a study about their use of nano-sized particles to release therapeutic drugs that are designed to relieve chronic inflammation. From the Mar. 18, 2013 news release on EurekAlert,

Inflammation is the body’s natural defense mechanism against invading organisms and tissue injury. In acute inflammation, the pathogen or inflammatory mediators are cleared away and homeostasis is reached, however in chronic inflammatory states, this resolving response is impaired, leading to chronic inflammation and tissue damage. It is now widely believed that an impaired resolution of inflammation is a major contributing factor to the progression of a number of devastating diseases such as atherosclerosis, arthritis, and neurodegenerative diseases, in addition to cancer. Since the level of inflammation in these diseases is very high—targeted therapeutic solutions are required to help keep inflammation contained.

A new study from researchers at Brigham and Women’s Hospital (BWH), Columbia University Medical Center, Icahn School of Medicine at Mount Sinai, and Massachusetts Institute of Technology presents the development of tiny nanomedicines in the sub 100 nm range (100,000 times smaller than the diameter of a human hair strand) that are capable of encapsulating and releasing an inflammation-resolving peptide drug. The authors showed that these nanoparticles are potent pro-resolving nanomedicines, capable of selectively homing to sites of tissue injury in mice, and releasing their therapeutic payload in a controlled manner over time. Uniquely, these nanoparticles are designed to target the extracellular microenvironment of inflamed tissues. The particles then slowly release their potent inflammation-resolving payload such that it can diffuse through the inflamed tissue. There the drug binds to receptors on the plasma membrane of activated white blood cells and causes them to become more quiescent.

The research will be published some time this week (week of Mar. 18, 2013) by the Proceedings of the National Academy of Science. The news release offers more detail about the work,

“The beauty of this approach is that it takes advantage of nature’s own design for preventing inflammation-induced damage, which, unlike many other anti-inflammatory strategies, does not compromise host defense and promotes tissue repair,” said Ira Tabas, MD, PhD, physician-scientist at Columbia University Medical Center and co-senior author of this study.

“The development of self-assembled targeted nanoparticles which are capable of resolving inflammation has broad application in medicine including the treatment of atherosclerosis,” said Omid Farokhzad, MD, physician-scientist at BWH, and a co-senior author of this study.

Polymers consisting of three chains attached end-to-end were developed as building blocks for the engineering of self-assembled targeted nanoparticles; one chain enabled the entrapment and controlled release of the therapeutic payload, in this case a peptide which mimics the pro-resolving properties of the Annexin A1 protein. Another chain conferred stealth properties to the nanoparticles, enabling their long-circulation after systemic administration. Yet a third chain gave homing capability to the nanoparticles to target the collagen IV protein to the vascular wall. As such these nanoparticles are capable of selectively sticking to injured vasculature allowing their therapeutic anti-inflammatory cargo to be released where it is needed to effectively promote inflammation resolution in a deliberate and targeted manner.

“These targeted polymeric nanoparticles are capable of stopping neutrophils, which are the most abundant form of white blood cells, from infiltrating sites of disease or injury at very small doses. This action stops the neutrophils from secreting further signaling molecules which can lead to a constant hyper-inflammatory state and further disease complications,” said Nazila Kamaly, PhD, a postdoctoral fellow at BWH and co-lead author of this study.

“Nanoparticles that selectively bind to injured vasculature could have a profound impact in prevalent diseases, such as atherosclerosis, where damaged or comprised vasculature underlie the pathology. This work offers a novel targeted nanomedicine to the burgeoning field of inflammation-resolution, a field previously pioneered by BWH’s Dr. Charles Serhan,” said Gabrielle Fredman, PhD, a post-doctoral fellow at Columbia University Medical Center and co-lead author of this study.

These new developments have led the researchers to start investigating the potential of these pro-resolving nanomedicines for their effects on shrinking atherosclerotic plaques, and these studies are currently underway.

This news release does not offer any information as to what type of studies might be underway. My guess is that we are still years away from human clinical trials. Azonano also features this work in a Mar. 19, 2013 news item.

Study tracks evolution of world’s first 500 bio-nano firms

Monday, February 18th, 2013

Elicia Maine, a professor at Simon Fraser University’s Beedie School of Business, is presenting right now (9:45 am – 12:45 pm EST, Feb. 18, 2013) at the AAAS (American Association for the Advancement of Science) 2013 meeting in Boston, Massachusetts in a session titled, Confluence of Streams of Knowledge: Biotechnology and Nanotechnology, about her study on bio-nano firms. Here’s more about her and her work in a Feb. 15, 2013 news release from Simon Fraser University (SFU), Note: I have removed a link,

Elicia Maine, an SFU associate professor of technology management and strategy at the Beedie School of Business, has co-authored a study that puts bio-nano firms under the microscope.

They are a new breed of business at the intersection of biotechnology and nanotechnology.

Maine will unveil a groundbreaking study on bio-nano firms in a seminar she has co-organized (with James Utterback, a Massachusetts Institute of Technology professor) at the world’s largest science research meeting.

Maine’s presentation, followed by a panel discussion, will take place at the annual American Association for the Advancement of Science (AAAS) convention in Boston, Massachusetts on Monday, Feb. 18, 9:45 a.m.-12:45 p.m. (Pacific time) Location: Room 300, Hynes Convention Centre.

The study, the first of its kind, tracks the evolution of the world’s first 500 bio-nano firms from their inception until now. “We are interested in seeing when these firms developed or acquired nanotechnology and biotechnology capabilities, and what they have done with those capabilities in terms of integrating the knowledge into new products and processes,” says Maine.

“We’ve classified the pioneers of this new breed of firms at the confluence of biotechnology and nanotechnology based on their primary role in innovation. They cover the areas of biopharma, drug delivery, diagnostics, biomaterials, medical devices, suppliers and instrumentation, and bioinformatics.”

Unfortunately, this is an unpublished study (I haven’t been able to find any reference to it online) but there is a video of Maine talking about her research on bio-nano firms,

ETA Feb. 21, 2012, There was a second news release from SFU dated Feb. 18, 2012, which provided some additional information and quotes about Maine’s research,

The study’s authors have identified, classified and analysed more than 500 of the world’s first companies in the emerging bio-nano sector. Their data shows these companies are taking hold not just in technology hotbeds such as California’s Silicon Valley and the northeastern United States but also across the country, and in Europe.

“We have watched the ecosystem emerge in terms of the number and type of firms entering,” says Maine.  “This confluence of technology silos in the emerging bio-nano sector is enabling radical innovation, new products and connections that didn’t exist before. Some of the things we’re talking about are targeted drug delivery, tissue engineering, enhanced medical diagnostics and new therapeutics.”

Between 2005 and 2011, the number of bio-nano firms nearly doubled to 507, with more than 100 of them emerging in North America alone.

Skills training: get ready for the robots

Tuesday, February 12th, 2013

If the boffins at the Massachusetts Institute of Technology (MIT) are right, soon we may be learning alongside robots and using the same techniques.  Helen Knight’s Feb. 11, 2013 news release for MIT highlights a recent study showing that robots, like humans, learn better if they cross-train. From the news release,

Robots are increasingly being used in the manufacturing industry to perform tasks that bring them into closer contact with humans. But while a great deal of work is being done to ensure robots and humans can operate safely side-by-side, more effort is needed to make robots smart enough to work effectively with people, says Julie Shah, an assistant professor of aeronautics and astronautics at MIT and head of the Interactive Robotics Group in the Computer Science and Artificial Intelligence Laboratory (CSAIL).

“People aren’t robots, they don’t do things the same way every single time,” Shah says. “And so there is a mismatch between the way we program robots to perform tasks in exactly the same way each time and what we need them to do if they are going to work in concert with people.”

Most existing research into making robots better team players is based on the concept of interactive reward, in which a human trainer gives a positive or negative response each time a robot performs a task.

However, human studies carried out by the military have shown that simply telling people they have done well or badly at a task is a very inefficient method of encouraging them to work well as a team.

Here’s the experiment Shah and her student performed,

So Shah and PhD student Stefanos Nikolaidis began to investigate whether techniques that have been shown to work well in training people could also be applied to mixed teams of humans and robots. One such technique, known as cross-training, sees team members swap roles with each other on given days. “This allows people to form a better idea of how their role affects their partner and how their partner’s role affects them,” Shah says.

In a paper to be presented at the International Conference on Human-Robot Interaction in Tokyo in March [2013], Shah and Nikolaidis will present the results of experiments they carried out with a mixed group of humans and robots, demonstrating that cross-training is an extremely effective team-building tool.

More specifically,

To allow robots to take part in the cross-training experiments, the pair first had to design a new algorithm to allow the devices to learn from their role-swapping experiences. So they modified existing reinforcement-learning algorithms to allow the robots to take in not only information from positive and negative rewards, but also information gained through demonstration. In this way, by watching their human counterparts switch roles to carry out their work, the robots were able to learn how the humans wanted them to perform the same task.

Each human-robot team then carried out a simulated task in a virtual environment, with half of the teams using the conventional interactive reward approach, and half using the cross-training technique of switching roles halfway through the session. Once the teams had completed this virtual training session, they were asked to carry out the task in the real world, but this time sticking to their own designated roles.

Shah and Nikolaidis found that the period in which human and robot were working at the same time — known as concurrent motion — increased by 71 percent in teams that had taken part in cross-training, compared to the interactive reward teams. They also found that the amount of time the humans spent doing nothing — while waiting for the robot to complete a stage of the task, for example — decreased by 41 percent.

What’s more, when the pair studied the robots themselves, they found that the learning algorithms recorded a much lower level of uncertainty about what their human teammate was likely to do next — a measure known as the entropy level — if they had been through cross-training.

Finally, when responding to a questionnaire after the experiment, human participants in cross-training were far more likely to say the robot had carried out the task according to their preferences than those in the reward-only group, and reported greater levels of trust in their robotic teammate. “This is the first evidence that human-robot teamwork is improved when a human and robot train together by switching roles, in a manner similar to effective human team training practices,” Nikolaidis says.

Shah believes this improvement in team performance could be due to the greater involvement of both parties in the cross-training process. “When the person trains the robot through reward it is one-way: The person says ‘good robot’ or the person says ‘bad robot,’ and it’s a very one-way passage of information,” Shah says. “But when you switch roles the person is better able to adapt to the robot’s capabilities and learn what it is likely to do, and so we think that it is adaptation on the person’s side that results in a better team performance.”

The work shows that strategies that are successful in improving interaction among humans can often do the same for humans and robots, says Kerstin Dautenhahn, a professor of artificial intelligence at the University of Hertfordshire in the U.K. “People easily attribute human characteristics to a robot and treat it socially, so it is not entirely surprising that this transfer from the human-human domain to the human-robot domain not only made the teamwork more efficient, but also enhanced the experience for the participants, in terms of trusting the robot,” Dautenhahn says.

The paper (Human-Robot Cross-Training: Computational Formulation, Modeling and Evaluation of a Human Team Training Strategy) written by Nikolaidis and Shah can be found here and the website for the conference (International Conference on Human-Robot Interaction [HRI]; 8th ACM [Association of Computing Machinery]/IEEE [Institute of Electrical and Electronics Engineers] Conference on Human-Robot Interaction) where it will be presented is here.

DNA tattoo patches

Friday, February 1st, 2013

Scientists seem fascinated with tattoos these days (my Dec. 4, 2012 posting, my Nov. 9, 2012 posting, March 20, 2012 posting amongst others). The latest work comes from the Massachusetts Institute of Technology (MIT) according to this Jan. 29, 2013 news item,

In a paper appearing in the Jan. 27 [2013] online issue of Nature Materials (“Polymer multilayer tattooing for enhanced DNA vaccination”), MIT researchers describe a new type of vaccine-delivery film that holds promise for improving the effectiveness of DNA vaccines. If such vaccines could be successfully delivered to humans, they could overcome not only the safety risks of using viruses to vaccinate against diseases such as HIV, but they would also be more stable, making it possible to ship and store them at room temperature.

The Jan. 29, 2013 MIT news release by Anne Trafton, which originated the news item, explains the interest in DNA vaccines and this proposed delivery system,

Vaccines usually consist of inactivated viruses that prompt the immune system to remember the invader and launch a strong defense if it later encounters the real thing. However, this approach can be too risky with certain viruses, including HIV.

In recent years, many scientists have been exploring DNA as a potential alternative vaccine. About 20 years ago, DNA coding for viral proteins was found to induce strong immune responses in rodents, but so far, tests in humans have failed to duplicate that success.

This type of vaccine delivery would also eliminate the need to inject vaccines by syringe, says Darrell Irvine, an MIT professor of biological engineering and materials science and engineering. “You just apply the patch for a few minutes, take it off and it leaves behind these thin polymer films embedded in the skin,” he says.

Scientists have had some recent success delivering DNA vaccines to human patients using a technique called electroporation. This method requires first injecting the DNA under the skin, then using electrodes to create an electric field that opens small pores in the membranes of cells in the skin, allowing DNA to get inside. However, the process can be painful and give varying results, Irvine says.

“It’s showing some promise but it’s certainly not ideal and it’s not something you could imagine in a global prophylactic vaccine setting, especially in resource-poor countries,” he says.

Irvine and Hammond took a different approach to delivering DNA to the skin, creating a patch made of many layers of polymers embedded with the DNA vaccine. These polymer films are implanted under the skin using microneedles that penetrate about half a millimeter into the skin — deep enough to deliver the DNA to immune cells in the epidermis, but not deep enough to cause pain in the nerve endings of the dermis.

Once under the skin, the films degrade as they come in contact with water, releasing the vaccine over days or weeks. As the film breaks apart, the DNA strands become tangled up with pieces of the polymer, which protect the DNA and help it get inside cells.

The researchers can control how much DNA gets delivered by tuning the number of polymer layers. They can also control the rate of delivery by altering how hydrophobic (water-fearing) the film is. DNA injected on its own is usually broken down very quickly, before the immune system can generate a memory response. When the DNA is released over time, the immune system has more time to interact with it, boosting the vaccine’s effectiveness.

The polymer film also includes an adjuvant — a molecule that helps to boost the immune response. In this case, the adjuvant consists of strands of RNA that resemble viral RNA, which provokes inflammation and recruits immune cells to the area.

The ability to provoke inflammation is one of the key advantages of the new delivery system, says Michele Kutzler, an assistant professor at Drexel University College of Medicine. Other benefits include targeting the wealth of immune cells in the skin, the use of a biodegradable delivery material, and the possibility of pain-free vaccine delivery, she says.

Here’s a citation and link to the paper,

Polymer multilayer tattooing for enhanced DNA vaccination by Peter C. DeMuth, Younjin Min, Bonnie Huang, Joshua A. Kramer, Andrew D. Miller, Dan H. Barouch, Paula T. Hammond, & Darrell J. Irvine. Nature Materials (2013) doi:10.1038/nmat3550 Published online 27 January 2013

The article is behind a paywall. And, for those who find images help to better understand,

Graphic: Christine Daniloff/MIT [downloaded from http://web.mit.edu/newsoffice/2013/vaccine-film-delivery-hiv-0127.html]

Graphic: Christine Daniloff/MIT [downloaded from http://web.mit.edu/newsoffice/2013/vaccine-film-delivery-hiv-0127.html]

Forbes magazine and US science culture

Thursday, December 27th, 2012

Forbes magazine, which is based in the US but now has editions produced in many countries, describes its focus as business and finance. So, it might seem a little unexpected to find a list of rising stars in the fields of science and health until one remembers the current fascination, worldwide, with innovation which often seems to mean science research which can be commercialized.

Forbes has just published its list of ’30 under 30′ rising stars in the fields of Science and Health Care. Pedro Valencia, who studied with and worked in Robert Langer’s lab at the Massachusetts Institute of Technology (MIT), was one of the 30 cited in the 2012 list. From the Dec. 27, 2012 news item on Azonano,

Valencia was cited for figuring out “how to more quickly synthesize nanoparticles that can be used to make drugs more effective and less toxic and to put multiple drugs inside the same nanotech medicine. This has resulted in many top-notch scientific publications and the formation of a start-up, Blend Therapeutics.”

Valencia was the recipient of the NSF Graduate Fellowship. He was co-advised by Professor Langer and Dr. Omid Farokhzad of the Brigham Women’s Hospital – Harvard Medical School.

Langer and Farokhzad were mentioned in my Oct. 28, 2011 posting about nanotechnology commercialization efforts,

… BIND Biosciences and Selecta Biosciences, two leading nanomedicine companies, announced today that they have entered into investment agreements with RUSNANO, a $10-billion Russian Federation fund that supports high-tech and nanotechnology advances.

RUSNANO is co-investing $25 million in BIND and $25 million in Selecta, for a total RUSNANO investment of $50 million within the total financing rounds of $94.5 million in the two companies combined. …

The proprietary technology platforms of BIND and Selecta originated in laboratories at Harvard Medical School directed by Professor Omid Farokhzad, MD, and in laboratories at MIT directed by Professor Robert Langer, ScD, a renowned scientist who is a recipient of the US National Medal of Science, the highest US honor for scientists, and is an inventor of approximately 850 patents issued or pending worldwide. Drs. Langer and Farokhzad are founders of both companies. [Farokhzad was featured in a recent Canadian Broadcasting Corporation {CBC}, Nature of Things, television episode about nanomedicine, titled More than human.] Professor Ulrich von Andrian, MD, PhD, head of the immunopathology laboratory at Harvard Medical School, is a founder of Selecta.

It is fascinating to observe not only the linkages between business and science/health but also the way in which those linkages contribute to a larger ‘science culture’, which includes science festivals, science-oriented popular culture, science talks for just a few examples.

Producing stronger silk musically

Wednesday, November 28th, 2012

Markus Buehler and his interdisciplinary team (my previous posts on their work includes Gossamer silk that withstands hurricane force winds and Music, math, and spiderwebs) have synthesized a new material based on spider silk. From the Nov. 28, 2012 news item on ScienceDaily,

Pound for pound, spider silk is one of the strongest materials known: Research by MIT’s [Massachusetts Institute of Technology] Markus Buehler has helped explain that this strength arises from silk’s unusual hierarchical arrangement of protein building blocks.

Now Buehler — together with David Kaplan of Tufts University and Joyce Wong of Boston University — has synthesized new variants on silk’s natural structure, and found a method for making further improvements in the synthetic material.

And an ear for music, it turns out, might be a key to making those structural improvements.

Here’s Buehler describing the work in an MIT video clip,

The Nov. 28, 2012 MIT news release by David Chandler provides more details,

Buehler’s previous research has determined that fibers with a particular structure — highly ordered, layered protein structures alternating with densely packed, tangled clumps of proteins (ABABAB) — help to give silk its exceptional properties. For this initial attempt at synthesizing a new material, the team chose to look instead at patterns in which one of the structures occurred in triplets (AAAB and BBBA).

Making such structures is no simple task. Kaplan, a chemical and biomedical engineer, modified silk-producing genes to produce these new sequences of proteins. Then Wong, a bioengineer and materials scientist, created a microfluidic device that mimicked the spider’s silk-spinning organ, which is called a spinneret.

Even after the detailed computer modeling that went into it, the outcome came as a bit of a surprise, Buehler says. One of the new materials produced very strong protein molecules — but these did not stick together as a thread. The other produced weaker protein molecules that adhered well and formed a good thread. “This taught us that it’s not sufficient to consider the properties of the protein molecules alone,” he says. “Rather, [one must] think about how they can combine to form a well-connected network at a larger scale.”

The different levels of silk’s structure, Buehler says, are analogous to the hierarchical elements that make up a musical composition — including pitch, range, dynamics and tempo. The team enlisted the help of composer John McDonald, a professor of music at Tufts, and MIT postdoc David Spivak, a mathematician who specializes in a field called category theory. Together, using analytical tools derived from category theory to describe the protein structures, the team figured out how to translate the details of the artificial silk’s structure into musical compositions.

The differences were quite distinct: The strong but useless protein molecules translated into music that was aggressive and harsh, Buehler says, while the ones that formed usable fibers sound much softer and more fluid.

Combining materials modeling with mathematical and musical tools, Buehler says, could provide a much faster way of designing new biosynthesized materials, replacing the trial-and-error approach that prevails today. Genetically engineering organisms to produce materials is a long, painstaking process, he says, but this work “has taught us a new approach, a fundamental lesson” in combining experiment, theory and simulation to speed up the discovery process.

Materials produced this way — which can be done under environmentally benign, room-temperature conditions — could lead to new building blocks for tissue engineering or other uses, Buehler says: scaffolds for replacement organs, skin, blood vessels, or even new materials for use in civil engineering.

It may be that the complex structures of music can reveal the underlying complex structures of biomaterials found in nature, Buehler says. “There might be an underlying structural expression in music that tells us more about the proteins that make up our bodies. After all, our organs — including the brain — are made from these building blocks, and humans’ expression of music may inadvertently include more information that we are aware of.”

“Nobody has tapped into this,” he says, adding that with the breadth of his multidisciplinary team, “We could do this — making better bio-inspired materials by using music, and using music to better understand biology.”

At the end of Chandler’s news release there’s a notice about a summer course with Markus Buehler,

For those interested in the work Professor Buehler is doing, you may also be interested to know that he is offering a short course on campus this summer called Materials By Design.

Materials By Design
June 17-20, 2013
shortprograms.mit.edu/mbd

Through lectures and hands-on labs, participants will learn how materials failure, studied from a first principles perspective, can be applied in an effective “learning-from-failure approach” to design and make novel materials. Participants will also learn how superior material properties in nature and biology can be mimicked in bioinspired materials for applications in new technology. This course will be of interest to scientists, engineers, managers, and policy makers working in the area of materials design, development, manufacturing, and testing. [emphasis mine]

I wasn’t expecting to see managers and policy makers as possible students for this course.

By the way, Buehler is not the only scientist to make a connection between music and biology (although he seems to be the only person using the concept for applications), there’s also geneticist and biophysicist, Mae Wan Ho and her notion of quantum jazz. From the Quantum Jazz Biology* article by David Reilly in the June 23, 2010 Isis Report,

I use the analogy of ‘quantum jazz’ to express the quantum coherence of the organism. It goes through a fantastic range of space and time scales, from the tiniest atom or subatomic particle to the whole organism and beyond. Organisms communicate with other organisms, and are attuned to natural rhythms, so they have circadian rhythms, annual rhythms, and so on. At the other extreme, you have very fast reactions that take place in femtoseconds. And all these rhythms are coordinated, there is evidence for that.