Tag Archives: nanobots

Canada’s Nanorobotics Laboratory unveils its ‘medical interventional infrastructure’

Located at the Polytechnique Montréal (Canada), the Nanorobotics Laboratory has built a one-of-a-kind ‘medical interventional infrastructure’, the result of a $4.6M investment from various levels of government and from private enterprise.

Before getting to the news release, here’s a video featuring Prof. Sylvain Martel who discusses his work by referencing the movie, Fantastic Voyage. There are subtitles for those whose French fails them,

From an Aug. 24, 2016 Polytechnique Montréal news release (also on EurekAlert),

Fifty years to the day after the film Fantastic Voyage was first shown in theatres, the Polytechnique Montréal Nanorobotics Laboratory is unveiling a unique medical interventional infrastructure devoted to the fight against cancer. The outcome of 15 years of research conducted by Professor Sylvain Martel and his team, it enables microscopic nanorobotic agents to be guided through the vascular systems of living bodies, delivering drugs to targeted areas.

An action-packed 100,000-kilometre journey in the human body

Fantastic Voyage recounted the adventure of a team of researchers shrunk to microscopic size who, aboard a miniature submarine, travelled into a patient’s body to conduct a medical operation in a surgically inoperable area. This science fiction classic has now been eclipsed by procedures and protocols developed by Professor Martel’s multidisciplinary team comprising engineers, scientists and experts from several medical specialties working together on these projects that herald the future of medicine.

“Our work represents a new vision of cancer treatments, with our goal being to develop the most effective transportation systems for the delivery of therapeutic agents right to tumour cells, to areas unreachable by conventional treatments,” says Professor Martel, holder of the Canada Research Chair in Medical Nanorobotics and Director of the Polytechnique Montréal Nanorobotics Laboratory.

Conveying nanorobotic agents into the bloodstream to reach the targeted area right up to the tiniest capillaries without getting lost in this network stretching about 100,000 kilometres—two-and-a-half times the Earth’s circumference—is a scenario that has been turned into reality. This is an adventure-filled journey for these microscopic vehicles that must confront the powerful onslaught of arterial blood flow, the mazes of the vascular network and the narrowness of the capillaries—just like the film’s heroes!

“Doctors” invisible to the naked eye

To conduct this fantastic voyage, Professor Martel’s team is developing various procedures, often playing a pioneering role. These include navigating carriers just a fraction of the thickness of a hair through the arteries using a clinical magnetic resonance imaging (MRI) platform, the first in the world to achieve this in a living organism, in 2006. This exploit was followed in 2011 by the guidance of drug-loaded micro-transporters into the liver of a rabbit.

Limits to the miniaturization of artificial nanorobots prevent them from penetrating the smallest blood vessels, however. For this, Professor Martel plans to have them play the role of Trojan horses, enclosing an “army” of special bacteria loaded with drugs that they will release at the edges of these small vessels.

Able to follow paths smaller than a red blood cell, these self-propelled bacteria move at high speed (200 microns per second, or 200 times their size per second). Once they are inside a tumour, they are able to naturally detect hypoxic (oxygen-starved) zones, which are the most active zones and the hardest to treat by conventional means, including radiotherapy, and then deliver the drug.

Professor Martel’s team has succeeded in using this procedure to administer therapeutic agents in colorectal tumours in mice, guiding them through a magnetic field. This has just been the subject of an article in the renowned journal Nature Nanotechnology, titled Magneto-gerotactic Bacteria Deliver Drug-containing Nanoliposomes to Tumour Hypoxic Regions. “This advanced procedure, which provides optimal targeting of a tumour while preserving surrounding healthy organs and tissue, unlike current chemotherapy or radiotherapy, heralds a new era in cancer treatment,” says Dr. Gerald Batist, Director of the McGill Centre for Translational Research in Cancer, based at the Jewish General Hospital, which is collaborating on the project.

Professor Martel’s projects also focus on the inaccessibility of certain parts of the body, such as the brain, to transporting agents. In 2015, his team also stood out by successfully opening a rat’s blood-brain barrier, temporarily and without damage, providing access to targeted areas of the brain. This feat was achieved through a slight rise in temperature caused by exposing nanoparticles to a radiofrequency field.

“At present, 98% of drug molecules cross the blood-brain barrier only with great difficulty,” notes Dr. Anne-Sophie Carret, a specialist in hematology-oncology at Montréal’s Centre hospitalier universitaire Sainte-Justine and one of the doctors collaborating on the project. “This means surgery is often the only way to treat some patients who have serious brain diseases. But certain tumours are inoperable because of their location. Radiation therapy, for its part, is not without medium- and long-term risk for the brain. This work therefore offers real hope to patients suffering from a brain tumour.”

Here’s who invested, how much they invested, and what the Nanorobotics Laboratory got for its money,

This new investment in the Nanorobotics Laboratory represents $4.6 million in infrastructure, with contributions of $1.85 million each from the Canada Foundation for Innovation (CFI), and the Government of Québec. Companies including Siemens Canada and Mécanik have also made strategic contributions to the project. This laboratory now combines platforms to help develop medical protocols for transferring the procedures developed by Professor Martel to a
clinical setting.

The laboratory contains the following equipment:

  • a clinical MRI platform to navigate microscopic carriers directly into specific areas in the vascular system and for 3D visualization of these carriers in the body;
  • a specially-developed platform that generates the required magnetic field sequences to guide special bacteria loaded with therapeutic agents into tumours;
  • a robotic station (consisting of a robotized bed) for moving a patient from one platform to another;
  • a hyperthermia platform for temporary opening of the blood-brain barrier;
  • a mobile X-ray system;
  • a facility to increase the production of these cancer-fighting bacteria.

Sylvain Martel’s most recent work with nanorobotic agents (as cited in the news release) was featured here in an Aug. 16, 2016 post.

Public relations (PR) and nanotechnology

Shannon Bowen of the University of South Carolina has written an March 18, 2016 essay about public relations (PR) and nanotechnology for PR Week,

As a responsible public relations professional, you try to be proactive, keeping up with changes in technology and the resulting demands from your organization or clients. More companies are becoming involved in nanotechnology, and PR pros should not treat the subject as some black hole from which to run. Issues surrounding nanotechnology will have to be dealt with, from media relations to issues management to ethics. Like neurotechnology, the field of nanotechnology is growing at an exponential rate. It is so new that no one is really sure what development will come next — nanotech researchers are currently developing specialty areas such as nanobiology, nanopharmacology, and nanorobots.

Maybe your organization or client has no interest in nanotechnology yet, but as an up-to-date PR pro, you should be able to help separate myth or fear from fact if needed. The implications of nanotechnology in the medical field alone are numerous. In the book The Future of the Mind, physicist Michio Kaku writes of nanobots:

“On the surface, the nanobot is simple: an atomic machine with arms and clippers that grabs molecules, cuts them at specific points, and then splices them back together. By cutting and pasting various atoms, the nanobot can create almost any know molecule, like a magician pulling something out of a hat. It can also self-reproduce, so it is necessary to build only one nanobot. This nanobot will then take raw materials, digest them, and create millions of other nanobots.”

Bowen seems to have discovered nanotechnology relatively recently and seems not to realize how prevalent nanotechnology-enabled products are already,

Soon, nanotech will be unavoidable. It will cut across vast sectors of industry, from computing to defense to mechanical engineering of consumer products. All these business sectors will need communication about safety protocols, privacy concerns, public policy, regulation and lobbying, and the pros and cons of using nanotech. Public relations for the nano world will become huge — figuratively speaking.

It’s an interesting essay with some good points but Bowen is not very well informed about nanotechnology. For example, there’s this from her list of ethical and social issues,

Research ethics
Are some research projects, such as military projects, too dangerous to pursue?

Nano medications
In addition to safety, this also raises privacy concerns about tracking. Human trials of such drugs begin in about two years.

The ship has sailed with regard to military research. So, the question turns from “Should we be doing this?” to “Should we continue doing this? and, possibly, Can we get everyone (all countries) to agree to stop?”

And, there are already human trials of nanotechnology-enabled drug delivery and other biomedical applications. For example there’s this from a March 21, 2016 California Institute of Technology (CalTech) news release about nanoparticles for cancer therapy,

These nanoparticles are currently being tested in a number of phase-II clinical trials. (Information about trials of the nanoparticles, denoted CRLX101, is available at http://www.clinicaltrials.gov.

For anyone unfamiliar with the phases for clinical trials, there’s this from Patients at Heart website on the Clinical Trials Essentials webpage in the section on Research Phases,

Target Patient Population Average Number of Patients
Phase I Healthy patients 20 to 80 participants
Phase II First evaluation in patients with the target disease 100 to 300 participants
Phase III Patients with the target disease 300 to 3,000 participants
Health Canada approval for use in the general population
Phase IV Patients with the target disease Variable – large numbers

Getting back to the essay, as Bowen notes there is a field designated as nanoethics. I found this Nanoethics Group based at California Polytechnic State University and this NanoEthics journal. I’m sure there’s much more out there should you care to search.

Nanotechnology and cybersecurity risks

Gregory Carpenter has written a gripping (albeit somewhat exaggerated) piece for Signal, a publication of the  Armed Forces Communications and Electronics Association (AFCEA) about cybersecurity issues and  nanomedicine endeavours. From Carpenter’s Jan. 1, 2016 article titled, When Lifesaving Technology Can Kill; The Cyber Edge,

The exciting advent of nanotechnology that has inspired disruptive and lifesaving medical advances is plagued by cybersecurity issues that could result in the deaths of people that these very same breakthroughs seek to heal. Unfortunately, nanorobotic technology has suffered from the same security oversights that afflict most other research and development programs.

Nanorobots, or small machines [or nanobots[, are vulnerable to exploitation just like other devices.

At the moment, the issue of cybersecurity exploitation is secondary to making nanobots, or nanorobots, dependably functional. As far as I’m aware, there is no such nanobot. Even nanoparticles meant to function as packages for drug delivery have not been perfected (see one of the controversies with nanomedicine drug delivery described in my Nov. 26, 2015 posting).

That said, Carpenter’s point about cybersecurity is well taken since security features are often overlooked in new technology. For example, automated banking machines (ABMs) had woefully poor (inadequate, almost nonexistent) security when they were first introduced.

Carpenter outlines some of the problems that could occur, assuming some of the latest research could be reliably  brought to market,

The U.S. military has joined the fray of nanorobotic experimentation, embarking on revolutionary research that could lead to a range of discoveries, from unraveling the secrets of how brains function to figuring out how to permanently purge bad memories. Academia is making amazing advances as well. Harnessing progress by Harvard scientists to move nanorobots within humans, researchers at the University of Montreal, Polytechnique Montreal and Centre Hospitalier Universitaire Sainte-Justine are using mobile nanoparticles inside the human brain to open the blood-brain barrier, which protects the brain from toxins found in the circulatory system.

A different type of technology presents a risk similar to the nanoparticles scenario. A DARPA-funded program known as Restoring Active Memory (RAM) addresses post-traumatic stress disorder, attempting to overcome memory deficits by developing neuroprosthetics that bridge gaps in an injured brain. In short, scientists can wipe out a traumatic memory, and they hope to insert a new one—one the person has never actually experienced. Someone could relish the memory of a stroll along the French Riviera rather than a terrible firefight, even if he or she has never visited Europe.

As an individual receives a disruptive memory, a cyber criminal could manage to hack the controls. Breaches of the brain could become a reality, putting humans at risk of becoming zombie hosts [emphasis mine] for future virus deployments. …

At this point, the ‘zombie’ scenario Carpenter suggests seems a bit over-the-top but it does hearken to the roots of the zombie myth where the undead aren’t mindlessly searching for brains but are humans whose wills have been overcome. Mike Mariani in an Oct. 28, 2015 article for The Atlantic has presented a thought-provoking history of zombies,

… the zombie myth is far older and more rooted in history than the blinkered arc of American pop culture suggests. It first appeared in Haiti in the 17th and 18th centuries, when the country was known as Saint-Domingue and ruled by France, which hauled in African slaves to work on sugar plantations. Slavery in Saint-Domingue under the French was extremely brutal: Half of the slaves brought in from Africa were worked to death within a few years, which only led to the capture and import of more. In the hundreds of years since, the zombie myth has been widely appropriated by American pop culture in a way that whitewashes its origins—and turns the undead into a platform for escapist fantasy.

The original brains-eating fiend was a slave not to the flesh of others but to his own. The zombie archetype, as it appeared in Haiti and mirrored the inhumanity that existed there from 1625 to around 1800, was a projection of the African slaves’ relentless misery and subjugation. Haitian slaves believed that dying would release them back to lan guinée, literally Guinea, or Africa in general, a kind of afterlife where they could be free. Though suicide was common among slaves, those who took their own lives wouldn’t be allowed to return to lan guinée. Instead, they’d be condemned to skulk the Hispaniola plantations for eternity, an undead slave at once denied their own bodies and yet trapped inside them—a soulless zombie.

I recommend reading Mariani’s article although I do have one nit to pick. I can’t find a reference to brain-eating zombies until George Romero’s introduction of the concept in his movies. This Zombie Wikipedia entry seems to be in agreement with my understanding (if I’m wrong, please do let me know and, if possible, provide a link to the corrective text).

Getting back to Carpenter and cybersecurity with regard to nanomedicine, while his scenarios may seem a trifle extreme it’s precisely the kind of thinking you need when attempting to anticipate problems. I do wish he’d made clear that the technology still has a ways to go.

Canada has a nanotechnology industry? and an overview of the US situation

It’s always interesting to get some insight into how someone else sees the nanotechnology effort in Canada.

First, there have been two basic approaches internationally. Some countries have chosen to fund nanotechnology/nanoscience research through a national initiative/project/council/etc. Notably the US, the UK, China, and Russia, amongst others, have followed this model. For example, the US National Nanotechnology Initiative (NNI)  (a type of hub for research, communication, and commercialization efforts) has been awarded a portion of the US budget every year since 2000. The money is then disbursed through the National Science Foundation.

Canada and its nanotechnology industry efforts

By contrast, Canada has no such line item in its national budget. There is a National Institute of Nanotechnology (NINT) but it is one of many institutes that help make up Canada’s National Research Council. I’m not sure if this is still true but when it was first founded, NINT was funded in part by the federal government and in part by the province of Alberta where it is located (specifically, in Edmonton at the University of Alberta). They claim the organization has grown since its early days although it looks like it’s been shrinking. Perhaps some organizational shuffles? In any event, support for the Canadian nanotechnology efforts are more provincial than federal. Alberta (NINT and other agencies) and Québec (NanoQuébec, a provincially funded nano effort) are the standouts, with Ontario (nano Ontario, a self-organized not-for-profit group) following closely. The scene in Canada has always seemed fragmented in comparison to the countries that have nanotechnology ‘hubs’.

Patrick Johnson in a Dec. 22, 2015 article for Geopolitical Monitor offers a view which provides an overview of nanotechnology in the US and Canada,  adds to the perspective offered here, and, at times, challenges it (Note: A link has been added),

The term ‘nanotechnology’ entered into the public vernacular quite suddenly around the turn of the century, right around the same time that, when announcing the US National Nanotechnology Initiative (NNI) in 2001 [2000; see the American Association for the Advancement of Science webpage on Historical Trends in Federal R&D, scroll down to the National Nanotechnology Initiative and click on the Jpg or Excel links], President Bill Clinton declared that it would one day build materials stronger than steel, detect cancer at its inception, and store the vast records of the Library of Congress in a device the size of a sugar cube. The world of science fiction took matters even further. In his 2002 book Prey, Michael Creighton [Michael Crichton; see Wikipedia entry] wrote of a cloud of self-replicating nanorobots [also known as, nanobots or self-assemblers] that terrorize the good people of Nevada when a science experiment goes terribly wrong.

Back then the hype was palpable. Federal money was funneled to promising nanotech projects as not to fall behind in the race to master this new frontier of science. And industry analysts began to shoot for the moon in their projections. The National Science Foundation famously predicted that the nanotechnology industry would be worth $1 trillion by the year 2015.

Well here we are in 2015 and the nanotechnology market was worth around $26 billion in [sic] last year, and there hasn’t even been one case of a murderous swarm of nanomachines terrorizing the American heartland. [emphasis mine]

Is this a failure of vision? No. If anything it’s only a failure of timing.

The nanotechnology industry is still well on its way to accomplishing the goals set out at the founding of the NNI, goals which at the time sounded utterly quixotic, and this fact is increasingly being reflected in year-on-year growth numbers. In other words, nanotechnology is still a game-changer in global innovation, it’s just taking a little longer than first expected.

The Canadian Connection

Although the Canadian government is not among the world’s top spenders on nanotechnology research, the industry still represents a bright spot in the future of the Canadian economy. The public-private engine [emphasis mine] at the center of Canada’s nanotech industry, the National Institute for Nanotechnology (NINT), was founded in 2001 with the stated goal of “increasing the competitiveness of Canadian companies; creating technology solutions to meet the needs of society; expanding training programs for researchers and entrepreneurs; and enhancing Canada’s stature in the world of nanotechnology.” This ambitious mandate that NINT set out for itself was to be accomplished over the course of two broad stages: first a ‘seeding’ phase of attracting promising personnel and coordinating basic research, and the then a ‘harvesting’ phase of putting the resulting nanotechnologies to the service of Canadian industry.

Recent developments in Canadian nanotechnology [emphasis mine] show that we have already entered that second stage where the concept of nanotechnology transitions from hopeful hypothetical to real-world economic driver

I’d dearly like to know which recent developments indicate Canada’s industry has entered a serious commercialization phase. (It’s one of the shortcomings of our effort that communication is not well supported.) As well, I’d like to know more about the  “… public-private engine at the center of Canada’s nanotech industry …” as Johnson seems to be referring to the NINT, which is jointly funded (I believe) by the federal government and the province of Alberta. There is no mention of private funding on their National Research Council webpage but it does include the University of Alberta as a major supporter.

I am intrigued and I hope there is more information to come.

US and its nanotechnology industry efforts

Dr. Ambika Bumb has written a Dec. 23, 2015 article for Tech Crunch which reflects on her experience as a researcher and entrepreneur in the context of the US NNI effort and includes a plea for future NNI funding [Note: One link added and one link removed],

Indeed, I am fortunate to be the CEO of a nanomedicine technology developer that extends the hands of doctors and scientists to the cellular and molecular level.

The first seeds of interest in bringing effective nano-tools into the hands of doctors and patients were planted in my mind when I did undergrad research at Georgia Tech.  That initial interest led to me pursuing a PhD at Oxford University to develop a tri-modal nanoparticle for imaging a variety of diseases ranging from cancers to autoimmune disorders.

My graduate research only served to increase my curiosity so I then did a pair of post-doctoral fellowships at the National Cancer Institute and the National Heart Lung and Blood Institute.  When it seemed that I was a shoe-in for a life-long academic career, our technology garnered much attention and I found myself in the Bay Area founding the now award-winning Bikanta [bikanta.com].

Through the National Nanotechnology Initiative (NNI) and Nanotechnology Research and Development Act of 2003, our federal government has invested $20 billion in nanoresearch in the past 13 years.  The return on that investment has resulted in 628 agency‐to‐agency collaborations, hundreds of thousands of publications, and more than $1 trillion in revenue generated from nano‐enabled products. [emphasis mine]

Given that medical innovations take a minimum of 10 years before they translate into a clinical product, already realizing a 50X return is an astounding achievement.  Slowing down would be counter-intuitive from an academic and business perspective.

Yet, that is what is happening.  Federal funding peaked half a decade ago in 2010.  [emphasis mine] NNI investments went from $1.58B in 2010 to $1.170B in 2015 (in constant dollars), a 26% drop.  The number of nano-related papers published in the US were roughly 25 thousand in 2013, while the EU and China produced 33 and 35 thousand, respectively.

History has shown repeatedly how the United States has lost an early competitive advantage in developing high‐value technologies to international competition when commercialization infrastructure was not adequately supported.

Examples include semiconductors, advanced batteries for vehicles, and cement‐based construction materials, all of which were originally developed in the United States, but are now manufactured elsewhere.

It is now time for a second era – NNI 2.0.  A return to higher and sustained investment, the purpose of NNI 2.0 should be not just foundational research but also necessary support for rapid commercialization of nanotechnology. The translation of bench science into commercial reality requires the partnership of academic, industrial, federal, and philanthropic players.

I’m not sure why there’s a difference between Johnson’s ” … worth around $26 billion in [sic] last year …] and Bumb’s “… return on that investment has resulted … more than $1 trillion in revenue generated from nano‐enabled products.” I do know there is some controversy as to what should or should not be included when estimating the value of the ‘nanotechnology enterprise’, for example, products that are only possible due to nanotechnology as opposed to products that already existed, such as golf clubs, but are enhanced by nanotechnology.

Bumb goes on to provide a specific example from her own experience to support the plea,

When I moved from the renowned NIH [US National Institutes of Health] on the east coast to the west coast to start Bikanta, one of the highest priority concerns was how we were going to develop nanodiamond technology without access to high-end characterization instrumentation to analyze the quality of our material.  Purchasing all that equipment was not financially viable or even wise for a startup.

We were extremely lucky because our proposal was accepted by the Molecular Foundry, one of five DOE [US Department of Energy]-funded nanoscience user facilities.  While the Foundry primarily facilitates basic nanoscience projects from academic and national laboratory users, Fortune 500 companies and startups like ours also take advantage of its capabilities to answer fundamental questions and conduct proof of concept studies (~10%).

Disregarding the dynamic intellectual community for a minute, there is probably more than $150M worth of instrumentation at the Foundry.  An early startup would never be able to dream of raising a first round that large.

One of the factors of Bikanta’s success is that the Molecular Foundry enabled us to make tremendous strides in R&D in just months instead of years.  More user facilities, incubator centers, and funding for commercializing nanotech are greatly needed.

Final comments

I have to thank Dr. Bumb for pointing out that 2010 was the peak for NNI funding (see the American Association for the Advancement of Science webpage on Historical Trends in Federal R&D, scroll down to the National Nanotechnology Initiative and click on the Jpg or Excel links). I erroneously believed (although I don’t appear to have written up my belief; if you find any such statement, please let me know so I can correct it) that the 2015 US budget was the first time the NNI experienced a drop in funding.

While I found Johnson’s article interesting I wasn’t able to determine the source for his numbers and some of his material had errors that can be identified immediately, e.g., Michael Creighton instead of Michael Crichton.

Science and the movies (Bond’s Spectre and The Martian)

There’s some nanotechnology in the new James Bond movie, Spectre, according to Johnny Brayson in his Nov. 5, 2015 (?) article for Bustle (Note: A link has been removed),

James Bond has always been known for his gadgets, and although Daniel Craig’s version of the character has been considerably less doohickey-heavy than past iterations, he’s still managed to make use of a few over the years, from his in-car defibrillator in Casino Royale to his biometric-coded gun in Skyfall. But Spectre, the newest Bond film, changes up the formula and brings more gadgets than fans have seen in years. There are returning favorites like a tricked out Aston Martin and an exploding watch, but there’s also a new twist on an old gadget that allows Bond to be tracked by his bosses, an injected microchip that records his every move. …

To Bond fans, though, the technology isn’t totally new. In Casino Royale, Bond is injected with a microchip that tracks his location and monitors his vital signs. However, when he’s captured by the bad guys, the device is cut out of his arm, rendering it useless. MI6 seems to have learned their lesson in Spectre, because this time around Bond is injected with Smart Blood, consisting of nanotechnology that does the same thing while flowing microscopically through his veins. As for whether it could really happen, the answer is not yet, but someday it could be.

Brayson provides an introduction to some of the exciting developments taking place scientifically in an intriguing way by relating those developments to a James Bond movie. Unfortunately, some of  his details  are wrong. For example, he is describing a single microchip introduced subcutaneously (under the skin) synonymously with ‘smart blood’ which would be many, many microchips prowling your bloodstream.

So, enjoy the article but exercise some caution. For example, this part in his article is mostly right (Note: Links have been removed),

However, there does actually exist nanotechnology that has been safely inserted into a human body — just not for the purposes of tracking.  Some “nanobots”, microscopic robots, have been used within the human eye to deliver drugs directly to the area that needs them [emphasis mine], and the idea is that one day similar nanobots will be able to be injected into one’s bloodstream to administer medication or even perform surgery. Some scientists even believe that a swarm of nanobots in the bloodstream could eventually make humans immune to disease, as the bots would simply destroy or fix any issues as soon as they arrive.

According to a Jan. 30, 2015 article by Jacopo Prisco for CNN, scientists at ETH Zurich were planning to start human clinical trials to test ‘micro or nanobots’ in the human eye. I cannot find any additional information about the proposed trials. Similarly, Israeli researcher Ido Bachelet announced a clinical trial of DNA nanobots on one patient to cure their leukemia (my Jan. 7, 2015 posting). An unsuccessful attempt to get updated information can found in a May 2015 Reddit Futurology posting.

The Martian

That film has been doing very well and, for the most part, seems to have gotten kudos for its science. However for those who like to dig down for more iinformation, Jeffrey Kluger’s Sept. 30, 2015 article for Time magazine expresses some reservations about the science while enthusing over its quality as a film,

… Go see The Martian. But still: Don’t expect all of the science to be what it should be. The hard part about good science fiction has always been the fiction part. How many liberties can you take and how big should they be before you lose credibility? In the case of The Martian, the answer is mixed.

The story’s least honest device is also its most important one: the massive windstorm that sweeps astronaut Mark Watney (Matt Damon) away, causing his crew mates to abandon him on the planet, assuming he has been killed. That sets the entire castaway tale into motion, but on a false note, because while Mars does have winds, its atmosphere is barely 1% of the density of Earth’s, meaning it could never whip up anything like the fury it does in the story.

“I needed a way to force the astronauts off the planet, so I allowed myself some leeway,” Weir conceded in a statement accompanying the movie’s release. …

It was exceedingly cool actually, and for that reason Weir’s liberty could almost be forgiven, but then the story tries to have it both ways with the same bit of science. When a pressure leak causes an entire pod on Watney’s habitat to blow up, he patches a yawning opening in what’s left of the dwelling with plastic tarp and duct tape. That might actually be enough to do the job in the tenuous atmosphere that does exist on Mars. But in the violent one Weir invents for his story, the fix wouldn’t last a day.

There’s more to this entertaining and educational article including embedded images and a video.

Building nanocastles in the sand

Scientists have taken inspiration from sandcastles to build robots made of nanoparticles. From an Aug. 5, 2015 news item on ScienceDaily,

If you want to form very flexible chains of nanoparticles in liquid in order to build tiny robots with flexible joints or make magnetically self-healing gels, you need to revert to childhood and think about sandcastles.

In a paper published this week in Nature Materials, researchers from North Carolina State University and the University of North Carolina-Chapel Hill show that magnetic nanoparticles encased in oily liquid shells can bind together in water, much like sand particles mixed with the right amount of water can form sandcastles.

An Aug. 5, 2015 North Carolina State University (NCSU) news release (also on EurekAlert) by Mick Kulikowski, which originated the news item, expands on the theme,

“Because oil and water don’t mix, the oil wets the particles and creates capillary bridges between them so that the particles stick together on contact,” said Orlin Velev, INVISTA Professor of Chemical and Biomolecular Engineering at NC State and the corresponding author of the paper.

“We then add a magnetic field to arrange the nanoparticle chains and provide directionality,” said Bhuvnesh Bharti, research assistant professor of chemical and biomolecular engineering at NC State and first author of the paper.

Chilling the oil is like drying the sandcastle. Reducing the temperature from 45 degrees Celsius to 15 degrees Celsius freezes the oil and makes the bridges fragile, leading to breaking and fragmentation of the nanoparticle chains. Yet the broken nanoparticles chains will re-form if the temperature is raised, the oil liquefies and an external magnetic field is applied to the particles.

“In other words, this material is temperature responsive, and these soft and flexible structures can be pulled apart and rearranged,” Velev said. “And there are no other chemicals necessary.”

The paper is also co-authored by Anne-Laure Fameau, a visiting researcher from INRA [French National Institute for Agricultural Research or Institut National de la Recherche Agronomique], France. …

Here’s a link to and a citation for the paper,

Nanocapillarity-mediated magnetic assembly of nanoparticles into ultraflexible filaments and reconfigurable networks by Bhuvnesh Bharti, Anne-Laure Fameau, Michael Rubinstein, & Orlin D. Velev. Nature Materials (2015) doi:10.1038/nmat4364 Published online 03 August 2015

This paper is behind a paywall.

I sing the body cyber: two projects funded by the US National Science Foundation

Points to anyone who recognized the reference to Walt Whitman’s poem, “I sing the body electric,” from his classic collection, Leaves of Grass (1867 edition; h/t Wikipedia entry). I wonder if the cyber physical systems (CPS) work being funded by the US National Science Foundation (NSF) in the US will occasion poetry too.

More practically, a May 15, 2015 news item on Nanowerk, describes two cyber physical systems (CPS) research projects newly funded by the NSF,

Today [May 12, 2015] the National Science Foundation (NSF) announced two, five-year, center-scale awards totaling $8.75 million to advance the state-of-the-art in medical and cyber-physical systems (CPS).

One project will develop “Cyberheart”–a platform for virtual, patient-specific human heart models and associated device therapies that can be used to improve and accelerate medical-device development and testing. The other project will combine teams of microrobots with synthetic cells to perform functions that may one day lead to tissue and organ re-generation.

CPS are engineered systems that are built from, and depend upon, the seamless integration of computation and physical components. Often called the “Internet of Things,” CPS enable capabilities that go beyond the embedded systems of today.

“NSF has been a leader in supporting research in cyber-physical systems, which has provided a foundation for putting the ‘smart’ in health, transportation, energy and infrastructure systems,” said Jim Kurose, head of Computer & Information Science & Engineering at NSF. “We look forward to the results of these two new awards, which paint a new and compelling vision for what’s possible for smart health.”

Cyber-physical systems have the potential to benefit many sectors of our society, including healthcare. While advances in sensors and wearable devices have the capacity to improve aspects of medical care, from disease prevention to emergency response, and synthetic biology and robotics hold the promise of regenerating and maintaining the body in radical new ways, little is known about how advances in CPS can integrate these technologies to improve health outcomes.

These new NSF-funded projects will investigate two very different ways that CPS can be used in the biological and medical realms.

A May 12, 2015 NSF news release (also on EurekAlert), which originated the news item, describes the two CPS projects,

Bio-CPS for engineering living cells

A team of leading computer scientists, roboticists and biologists from Boston University, the University of Pennsylvania and MIT have come together to develop a system that combines the capabilities of nano-scale robots with specially designed synthetic organisms. Together, they believe this hybrid “bio-CPS” will be capable of performing heretofore impossible functions, from microscopic assembly to cell sensing within the body.

“We bring together synthetic biology and micron-scale robotics to engineer the emergence of desired behaviors in populations of bacterial and mammalian cells,” said Calin Belta, a professor of mechanical engineering, systems engineering and bioinformatics at Boston University and principal investigator on the project. “This project will impact several application areas ranging from tissue engineering to drug development.”

The project builds on previous research by each team member in diverse disciplines and early proof-of-concept designs of bio-CPS. According to the team, the research is also driven by recent advances in the emerging field of synthetic biology, in particular the ability to rapidly incorporate new capabilities into simple cells. Researchers so far have not been able to control and coordinate the behavior of synthetic cells in isolation, but the introduction of microrobots that can be externally controlled may be transformative.

In this new project, the team will focus on bio-CPS with the ability to sense, transport and work together. As a demonstration of their idea, they will develop teams of synthetic cell/microrobot hybrids capable of constructing a complex, fabric-like surface.

Vijay Kumar (University of Pennsylvania), Ron Weiss (MIT), and Douglas Densmore (BU) are co-investigators of the project.

Medical-CPS and the ‘Cyberheart’

CPS such as wearable sensors and implantable devices are already being used to assess health, improve quality of life, provide cost-effective care and potentially speed up disease diagnosis and prevention. [emphasis mine]

Extending these efforts, researchers from seven leading universities and centers are working together to develop far more realistic cardiac and device models than currently exist. This so-called “Cyberheart” platform can be used to test and validate medical devices faster and at a far lower cost than existing methods. CyberHeart also can be used to design safe, patient-specific device therapies, thereby lowering the risk to the patient.

“Innovative ‘virtual’ design methodologies for implantable cardiac medical devices will speed device development and yield safer, more effective devices and device-based therapies, than is currently possible,” said Scott Smolka, a professor of computer science at Stony Brook University and one of the principal investigators on the award.

The group’s approach combines patient-specific computational models of heart dynamics with advanced mathematical techniques for analyzing how these models interact with medical devices. The analytical techniques can be used to detect potential flaws in device behavior early on during the device-design phase, before animal and human trials begin. They also can be used in a clinical setting to optimize device settings on a patient-by-patient basis before devices are implanted.

“We believe that our coordinated, multi-disciplinary approach, which balances theoretical, experimental and practical concerns, will yield transformational results in medical-device design and foundations of cyber-physical system verification,” Smolka said.

The team will develop virtual device models which can be coupled together with virtual heart models to realize a full virtual development platform that can be subjected to computational analysis and simulation techniques. Moreover, they are working with experimentalists who will study the behavior of virtual and actual devices on animals’ hearts.

Co-investigators on the project include Edmund Clarke (Carnegie Mellon University), Elizabeth Cherry (Rochester Institute of Technology), W. Rance Cleaveland (University of Maryland), Flavio Fenton (Georgia Tech), Rahul Mangharam (University of Pennsylvania), Arnab Ray (Fraunhofer Center for Experimental Software Engineering [Germany]) and James Glimm and Radu Grosu (Stony Brook University). Richard A. Gray of the U.S. Food and Drug Administration is another key contributor.

It is fascinating to observe how terminology is shifting from pacemakers and deep brain stimulators as implants to “CPS such as wearable sensors and implantable devices … .” A new category has been created, CPS, which conjoins medical devices with other sensing devices such as wearable fitness monitors found in the consumer market. I imagine it’s an attempt to quell fears about injecting strange things into or adding strange things to your body—microrobots and nanorobots partially derived from synthetic biology research which are “… capable of performing heretofore impossible functions, from microscopic assembly to cell sensing within the body.” They’ve also sneaked in a reference to synthetic biology, an area of research where some concerns have been expressed, from my March 19, 2013 post about a poll and synthetic biology concerns,

In our latest survey, conducted in January 2013, three-fourths of respondents say they have heard little or nothing about synthetic biology, a level consistent with that measured in 2010. While initial impressions about the science are largely undefined, these feelings do not necessarily become more positive as respondents learn more. The public has mixed reactions to specific synthetic biology applications, and almost one-third of respondents favor a ban “on synthetic biology research until we better understand its implications and risks,” while 61 percent think the science should move forward.

I imagine that for scientists, 61% in favour of more research is not particularly comforting given how easily and quickly public opinion can shift.

Université de Montréal (Canada) and nanobots breech blood-brain barrier to deliver drugs to the brain

In the spirit of full disclosure, the March 25, 2014 news item on ScienceDaily describing the research about breeching the blood-brain barrier uses the term nanorobotic agents rather than nanobots, a term which makes my headline a lot catchier although less accurate. Getting back to the research,

Magnetic nanoparticles can open the blood-brain barrier and deliver molecules directly to the brain, say researchers from the University of Montreal, Polytechnique Montréal, and CHU Sainte-Justine. This barrier runs inside almost all vessels in the brain and protects it from elements circulating in the blood that may be toxic to the brain. The research is important as currently 98% of therapeutic molecules are also unable to cross the blood-brain barrier.

“The barrier is temporary [sic] opened at a desired location for approximately 2 hours by a small elevation of the temperature generated by the nanoparticles when exposed to a radio-frequency field,” explained first author and co-inventor Seyed Nasrollah Tabatabaei. “Our tests revealed that this technique is not associated with any inflammation of the brain. This new result could lead to a breakthrough in the way nanoparticles are used in the treatment and diagnosis of brain diseases,” explained the co-investigator, Hélène Girouard. “At the present time, surgery is the only way to treat patients with brain disorders. Moreover, while surgeons are able to operate to remove certain kinds of tumors, some disorders are located in the brain stem, amongst nerves, making surgery impossible,” added collaborator and senior author Anne-Sophie Carret.

A March 25, 2015 University of Montreal news release (also on EurekAlert), which originated the news item, notes that the technique was tested or rats or mice (murine model) and explains how the technology breeches the blood-brain barrier,

Although the technology was developed using murine models and has not yet been tested in humans, the researchers are confident that future research will enable its use in people. “Building on earlier findings and drawing on the global effort of an interdisciplinary team of researchers, this technology proposes a modern version of the vision described almost 40 years ago in the movie Fantastic Voyage, where a miniature submarine navigated in the vascular network to reach a specific region of the brain,” said principal investigator Sylvain Martel. In earlier research, Martel and his team had managed to manipulate the movement of nanoparticles through the body using the magnetic forces generated by magnetic resonance imaging (MRI) machines.

To open the blood-brain barrier, the magnetic nanoparticles are sent to the surface of the blood-brain barrier at a desired location in the brain. Although it was not the technique used in this study, the placement could be achieved by using the MRI technology described above. Then, the researchers generated a radio-frequency field. The nanoparticles reacted to the radio-frequency field by dissipating heat thereby creating a mechanical stress on the barrier. This allows a temporary and localized opening of the barrier for diffusion of therapeutics into the brain.

The technique is unique in many ways. “The result is quite significant since we showed in previous experiments that the same nanoparticles can also be used to navigate therapeutic agents in the vascular network using a clinical MRI scanner,” Martel remarked. “Linking the navigation capability with these new results would allow therapeutics to be delivered directly to a specific site of the brain, potentially improving significantly the efficacy of the treatment while avoiding systemic circulation of toxic agents that affect healthy tissues and organs,” Carret added. “While other techniques have been developed for delivering drugs to the blood-brain barrier, they either open it too wide, exposing the brain to great risks, or they are not precise enough, leading to scattering of the drugs and possible unwanted side effect,” Martel said.

Although there are many hurdles to overcome before the technology can be used to treat humans, the research team is optimistic. “Although our current results are only proof of concept, we are on the way to achieving our goal of developing a local drug delivery mechanism that will be able to treat oncologic, psychiatric, neurological and neurodegenerative disorders, amongst others,” Carret concluded.

Here’s a link to and a citation for the paper,

Remote control of the permeability of the blood–brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery by Seyed Nasrollah Tabatabaei, Hélène Girouard, Anne-Sophie Carret, and Sylvain Martel.Journal of Controlled Release, Volume 206, 28 May 2015, Pages 49–57,  DOI: 10.1016/j.jconrel.2015.02.027  Available online 25 February 2015

This paper is behind a paywall.

For anyone unfamiliar with French, University of Montreal is Université de Montréal.

Maybe nano drug delivery not so magical after all?

There’s a lot of talk about the potential for a better way to treat disease with more accurate delivery of nanoparticle-based medicines to specific areas that need the treatment. For example, current treatments which shrink and eliminate cancer tumours also destroy healthy tissue and often have deleterious side effects while a nanoparticle-based treatment could seek out and eliminate the tumour only with few or no side effects. However, new research suggests that tumours may be more complex than previously understood.

From a Jan. 14, 2015 news item on Azonano,

Nanoparticle drugs–tiny containers packed with medicine and with the potential to be shipped straight to tumors–were thought to be a possible silver bullet against cancer. However new cancer drugs based on nanoparticles have not improved overall survival rates for cancer patients very much. Scientists at the University of North Carolina at Chapel Hill now think that failure may have less to do with the drugs and tumors than it does the tumor’s immediate surroundings.

The work, published in Clinical Cancer Research, merges relatively old and new ideas in cancer treatment, on one hand underscoring the importance of personalized medicine and on the other, reinforcing a relatively new idea that the tumor microenvironment might affect the delivery of drugs to tumors – a factor that may alter drug delivery from person to person, from cancer to cancer and even from tumor to tumor.

A Jan. 13, 2015 University of North Carolina news release (also on EurekAlert), which originated the news item, provides more details about the research,

“Tumors create bad neighborhoods,” said William Zamboni, the study’s senior author and an associate professor at the UNC Eshelman School of Pharmacy. “They spawn leaky, jumbled blood vessels that are like broken streets, blind alleys and busted sewers. There are vacant lots densely overgrown with collagen fibers. Immune-system cells patrolling the streets might be good guys turned bad, actually working for the tumor. And we’re trying to get a large truckload of medicine through all of that.”

In their work, Zamboni and colleagues from the UNC Lineberger Comprehensive Cancer Center and the UNC School of Medicine joined forces to see how much of the standard small-molecule cancer drug doxorubicin and its nanoparticle version, Doxil, actually made it into two varieties of triple-negative breast-cancer tumor models created by UNC’s Chuck Perou, the May Goldman Shaw Distinguished Professor of Molecular Oncology at the UNC School of Medicine and a professor at UNC Lineberger. Triple-negative breast cancer accounts for 10 to 17 percent of cases and has a poorer prognosis than other types of breast cancer.

At first, what they saw was no surprise: significantly more of the nanodrug Doxil made it into both triple-negative breast-cancer tumors compared with the standard small-molecule doxorubicin. “That’s nothing new,” Zamboni said. “We’ve seen that for twenty years.” They also saw the same amount of doxorubin in both tumors.

What did surprise them was that significantly more of the nanodrug Doxil – twice as much – was delivered to the C3-TAg triple-negative breast cancer tumor than to the T11 triple-negative breast cancer tumor.

“These tumors are subtypes of a subtype of one kind of cancer and are relatively closely related,” said Zamboni. “If the differences in delivering nanoagents to these two tumors are so significant, we can only imagine what the differences might be between breast cancer and lung cancer.”

Zamboni and his team suggest that better profiling of tumors and their microenvironments would allow doctors not only to better identify patients who would most benefit from nanoparticle-based cancer therapy, but also that clinicians may need to learn more about a patient’s tumor before prescribing treatment with one of the newer nanoparticle drugs.

This work gives the Israeli project I wrote about in my Jan. 7, 2015 post regarding a human clinical trial of nanobot delivery of a drug treatment (the world’s first) a new perspective. As a medical writer friend of mine (Susan Baxter) notes, these things are always more complicated than we think they’ll be and she adds tumours change over time.

Given how often we’ve discovered the human body is a complex, interwoven set of ecosystems, it’s perplexing that so much of the discussion around treatment is still  reductionist, i.e., drug kill tumour.

Getting back to this current research, here’s a link to and a citation for the paper,

Effects of Tumor Microenvironment Heterogeneity on Nanoparticle Disposition and Efficacy in Breast Cancer Tumor Models by Gina Song, David B. Darr, Charlene M. Santos, Mark Ross, Alain Valdivia, Jamie L. Jordan, Bentley R. Midkiff, Stephanie Cohen, Nana Nikolaishvili-Feinberg, C. Ryan Miller, Teresa K. Tarrant, Arlin B. Rogers, Andrew C. Dudley, Charles M. Perou, and William C. Zamboni. CCR-14-0493 Clin Cancer Res December 1, 2014 20 6083 doi: 10.1158/1078-0432 Published Online First September 17, 2014

This paper is behind a paywall of sorts. I haven’t seen this particular designation before but in addition to purchasing a subscription or short term access, there’s an option called: “patientACCESS – Patients/Caregivers desiring access to articles.” I’m not sure if that’s fee-based or not.