Tag Archives: Anne Trafton

DNA damage from engineered nanoparticles (zinc oxide, silver, silicon dioxide, cerium oxide and iron oxide)

Before launching into this research, there are a few provisos. This work was done in a laboratory, a highly specialized environment that does not mimic real-life conditions, and performed on animal cells (a hamster’s). As well, naturally occurring nanoparticles were not included (my Nov. 24, 2011 post has some information about naturally occurring nanomaterials including nanosilver which we have been ingesting for centuries).

That said, the studies from the Massachusetts Institute of Techology (MIT) and the Harvard School of Public Health (HSPH; last mentioned here in an April 2, 2014 post) are concerning (from an April 9, 2014 news item on Azonano).

A new study from MIT and the Harvard School of Public Health (HSPH) suggests that certain nanoparticles can also harm DNA. This research was led by Bevin Engelward, a professor of biological engineering at MIT, and associate professor Philip Demokritou, director of HSPH’s Center for Nanotechnology and Nanotoxicology.

The researchers found that zinc oxide nanoparticles, often used in sunscreen to block ultraviolet rays, significantly damage DNA. Nanoscale silver, which has been added to toys, toothpaste, clothing, and other products for its antimicrobial properties, also produces substantial DNA damage, they found.

The findings, published in a recent issue of the journal ACS Nano, relied on a high-speed screening technology to analyze DNA damage. This approach makes it possible to study nanoparticles’ potential hazards at a much faster rate and larger scale than previously possible.

More details about current testing requirements and the specific nanoparticles studied can be found in the April 8, 2014 MIT news release, which originated the news item,

The Food and Drug Administration does not require manufacturers to test nanoscale additives for a given material if the bulk material has already been shown to be safe. However, there is evidence that the nanoparticle form of some of these materials may be unsafe: Due to their immensely small size, these materials may exhibit different physical, chemical, and biological properties, and penetrate cells more easily.

“The problem is that if a nanoparticle is made out of something that’s deemed a safe material, it’s typically considered safe. There are people out there who are concerned, but it’s a tough battle because once these things go into production, it’s very hard to undo,” Engelward says.

The researchers focused on five types of engineered nanoparticles — silver, zinc oxide, iron oxide, cerium oxide, and silicon dioxide (also known as amorphous silica) — that are used industrially. Some of these nanomaterials can produce free radicals called reactive oxygen species, which can alter DNA. Once these particles get into the body, they may accumulate in tissues, causing more damage.

“It’s essential to monitor and evaluate the toxicity or the hazards that these materials may possess. There are so many variations of these materials, in different sizes and shapes, and they’re being incorporated into so many products,” says Christa Watson, a postdoc at HSPH and the paper’s lead author. “This toxicological screening platform gives us a standardized method to assess the engineered nanomaterials that are being developed and used at present.”

The researchers hope that this screening technology could also be used to help design safer forms of nanoparticles; they are already working with partners in industry to engineer safer UV-blocking nanoparticles. Demokritou’s lab recently showed that coating zinc oxide particles with a nanothin layer of amorphous silica can reduce the particles’ ability to damage DNA.

Given that Demokritou was part of a team that recently announced a new testing platform (Volumetric Centrifugation Method [VCM]) for nanoparticles as mentioned in my April 2, 2014 post, I was a little curious about the  platform for this project ( the CometChip) and, as always, curious about the results for all the tested engineered nanoparticles (Note: A link has been removed), from the news release,

Until now, most studies of nanoparticle toxicity have focused on cell survival after exposure. Very few have examined genotoxicity, or the ability to damage DNA — a phenomenon that may not necessarily kill a cell, but one that can lead to cancerous mutations if the damage is not repaired.

A common way to study DNA damage in cells is the so-called “comet assay,” named for the comet-shaped smear that damaged DNA forms during the test. The procedure is based on gel electrophoresis, a test in which an electric field is applied to DNA placed in a matrix, forcing the DNA to move across the gel. During electrophoresis, damaged DNA travels farther than undamaged DNA, producing a comet-tail shape.

Measuring how far the DNA can travel reveals how much DNA damage has occurred. This procedure is very sensitive, but also very tedious.

In 2010, Engelward and MIT professor Sangeeta Bhatia developed a much more rapid version of the comet assay, known as the CometChip. Using microfabrication technology, single cells can be trapped in tiny microwells within the matrix. This approach makes it possible to process as many as 1,000 samples in the time that it used to take to process just 30 samples — allowing researchers to test dozens of experimental conditions at a time, which can be analyzed using imaging software.

Wolfgang Kreyling, an epidemiologist at the German Research Center for Environmental Health who was not involved in the study, says this technology should help toxicologists catch up to the rapid rate of deployment of engineered nanoparticles (ENPs).

“High-throughput screening platforms are desperately needed,” Kreyling says. “The proposed approach will be not only an important tool for nanotoxicologists developing high-throughput screening strategies for the assessment of possible adverse health effects associated with ENPs, but also of great importance for material scientists working on the development of novel ENPs and safer-by-design approaches.”

Using the CometChip, the MIT and HSPH researchers tested the nanoparticles’ effects on two types of cells that are commonly used for toxicity studies: a type of human blood cells called lymphoblastoids, and an immortalized line of Chinese hamster ovary cells.

Zinc oxide and silver produced the greatest DNA damage in both cell lines. At a concentration of 10 micrograms per milliliter — a dose not high enough to kill all of the cells — these generated a large number of single-stranded DNA breaks.

Silicon dioxide, which is commonly added during food and drug production, generated very low levels of DNA damage. Iron oxide and cerium oxide also showed low genotoxicity.

Happily the researchers are taking a pragmatic approach to the results (from the news release),

More studies are needed to determine how much exposure to metal oxide nanoparticles could be unsafe for humans, the researchers say.

“The biggest challenge we have as people concerned with exposure biology is deciding when is something dangerous and when is it not, based on the dose level. At low levels, probably these things are fine,” Engelward says. “The question is: At what level does it become problematic, and how long will it take for us to notice?”

One of the areas of greatest concern is occupational exposure to nanoparticles, the researchers say. Children and fetuses are also potentially at greater risk because their cells divide more often, making them more vulnerable to DNA damage.

The most common routes that engineered nanoparticles follow into the body are through the skin, lungs, and stomach, so the researchers are now investigating nanoparticle genotoxicity on those cell types. They are also studying the effects of other engineered nanoparticles, including metal oxides used in printer and photocopier toner, which can become airborne and enter the lungs.

Kudos to the writer for the clarity and care shown here (I think it’s Anne Trafton but MIT is not including bylines as it did previously, so I’m uncertain).

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

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology by Christa Watson, Jing Ge, Joel Cohen, Georgios Pyrgiotakis, Bevin P. Engelward, and Philip Demokritou. ACS Nano, 2014, 8 (3), pp 2118–2133 DOI: 10.1021/nn404871p Publication Date (Web): March 11, 2014
Copyright © 2014 American Chemical Society

This article is behind a paywall.

A millionth of a trillionth of a gram: attoscale weight

Researchers at the Massachusetts Institute of Technology (MIT) have found a means of measuring particle weight, with increased accuracy, at the attoscale according to a Jan. 13, 2014 news item on ScienceDaily,

MIT engineers have devised a way to measure the mass of particles with a resolution better than an attogram — one millionth of a trillionth of a gram. Weighing these tiny particles, including both synthetic nanoparticles and biological components of cells, could help researchers better understand their composition and function.

The Jan. 13, 2014 MIT news release by Anne Trafton (also on EurekAlert), which originated the news item, describes the origins of the technology that the researchers adapted to achieve increased resolution,

The system builds on a technology previously developed by Scott Manalis, an MIT professor of biological and mechanical engineering, to weigh larger particles, such as cells. This system, known as a suspended microchannel resonator (SMR), measures the particles’ mass as they flow through a narrow channel.

By shrinking the size of the entire system, the researchers were able to boost its resolution to 0.85 attograms —more than a 30-fold improvement over the previous generation of the device.

“Now we can weigh small viruses, extracellular vesicles, and most of the engineered nanoparticles that are being used for nanomedicine,” says Selim Olcum, a postdoc in Manalis’ lab  …

Manalis first developed the SMR system in 2007 to measure the mass of living cells, as well as particles as small as a femtogram (one quadrillionth of a gram, or 1,000 attograms). Since then, his lab has used the device to track cell growth over time, measure cell density, and measure other physical properties, such as stiffness.

The original mass sensor consists of a fluid-filled microchannel etched in a tiny silicon cantilever that vibrates inside a vacuum cavity. As cells or particles flow through the channel, one at a time, their mass slightly alters the cantilever’s vibration frequency. The mass of the particle can be calculated from that change in frequency.

To make the device sensitive to smaller masses, the researchers had to shrink the size of the cantilever, which behaves much like a diving board, Olcum says. When a diver bounces at the end of a diving board, it vibrates with a very large amplitude and low frequency. When the diver plunges into the water, the board begins to vibrate much faster because the total mass of the board has dropped considerably.

To measure smaller masses, a smaller “diving board” is required. “If you’re measuring nanoparticles with a large cantilever, it’s like having a huge diving board with a tiny fly on it. When the fly jumps off, you don’t notice any difference. That’s why we had to make very tiny diving boards,” Olcum says.

In a previous study, researchers in Manalis’ lab built a 50-micron cantilever — about one-tenth the size of the cantilever used for measuring cells. That system, known as a suspended nanochannel resonator (SNR), was able to weigh particles as light as 77 attograms at a rate of a particle or two per second.

Here’s how the scientists accomplished their latest goal of getting more precise measurements of weight (from the news release),

The cantilever in the new version of the SNR device is 22.5 microns long, and the channel that runs across it is 1 micron wide and 400 nanometers deep. This miniaturization makes the system more sensitive because it increases the cantilever’s vibration frequency. At higher frequencies, the cantilever is more responsive to smaller changes in mass.

The researchers got another boost in resolution by switching the source for the cantilever’s vibration from an electrostatic to a piezoelectric excitation, which produces a larger amplitude and, in turn, decreases the impact of spurious vibrations that interfere with the signal they are trying to measure.

With this system, the researchers can measure nearly 30,000 particles in a little more than 90 minutes. “In the span of a second, we’ve got four or five particles going through, and we could potentially increase the concentration and have particles going through faster,” Cermak says.

To demonstrate the device’s usefulness in analyzing engineered nanoparticles, the MIT team weighed nanoparticles made of DNA bound to tiny gold spheres, which allowed them to determine how many gold spheres were bound to each DNA-origami scaffold. That information can be used to assess yield, which is important for developing precise nanostructures, such as scaffolds for nanodevices.

The researchers also tested the SNR system on biological nanoparticles called exosomes — vesicles that carry proteins, RNA, or other molecules secreted by cells — which are believed to play a role in signaling between distant locations in the body.

They found that exosomes secreted by liver cells and fibroblasts (cells that make up connective tissue) had different profiles of mass distribution, suggesting that it may be possible to distinguish vesicles that originate from different cells and may have different biological functions.

The researchers are now investigating using the SNR device to detect exosomes in the blood of patients with glioblastoma (GBM), a type of brain cancer. This type of tumor secretes large quantities of exosomes, and tracking changes in their concentration could help doctors monitor patients as they are treated.

Glioblastoma exosomes can now be detected by mixing blood samples with magnetic nanoparticles coated with antibodies that bind to markers found on vesicle surfaces, but the SNR could provide a simpler test.

Here’s a link to and a citation for the researchers’ abstract,

Weighing nanoparticles in solution at the attogram scale by Selim Olcuma, Nathan Cermak, Steven C. Wasserman, Kathleen S. Christine, Hiroshi Atsumi, Kris R. Payer, Wenjiang Shen, Jungchul Lee, Angela M. Belcher, Sangeeta N. Bhatia, and Scott R. Manalis. Proceedings of the National Academy of Sciences of the United States of America (PNAS), doi: 10.1073/pnas.1318602111 Published online Jan. 13, 2014

This article is behind a paywall.

Inspired by babies, scientists consdier popping nanoparticle pills and downing nanoparticle potions

Given the choice over injections or suppositories most of us will choose to take medication orally (pills or liquids). It may be a surprise to some but with all the talk about nanomedicine there has been a problem with using nanoparticles in an oral delivery system which scientists at the Brigham and Women’s Hospital (BWH) and Massachusetts Institute of Technology (MIT) have solved. From a Nov. 27, 2013 BWH news release, on EurekAlert,

… a study led by researchers at Brigham and Women’s Hospital (BWH) and Massachusetts Institute of Technology (MIT) is the first to report in the field of nanomedicine a new type of nanoparticle that can be successfully absorbed through the digestive tract. The findings may one day allow patients to simply take a pill instead of receiving injections.

Until recently, after being injected into the body, nanoparticles travelled to their destination, such as a tumor, by seeping through leaky vessels. The research team, led by Farokhzad [Omid Farokhzad, MD, director of the BWH Laboratory of Nanomedicine and Biomaterials, senior study author] and Robert Langer, ScD of MIT, developed nanoparticles that could reach the target site without relying on injection nor leaky vessels.

For nanoparticles to be taken orally they need to cross the intestinal lining. This lining is composed of a layer of epithelial cells joined together to form impenetrable barriers called tight junctions. To ensure that the nanoparticles could cross these barriers, the researchers took a cue from research on how babies absorb antibodies from their mothers’ milk. The antibodies would grab onto a receptor, known as neonatal Fc receptors, found on the cell surface. This gave them access across the cells of the intestinal lining into neighboring blood vessels.

Based on this knowledge, the researchers decorated nanoparticles with Fc proteins that targeted and bound to these receptors, which are also found in adult intestinal cells. After attaching to the receptors, the Fc-protein-decorated nanoparticles—toting their drug payload—are all absorbed into the intestinal lining and into the bloodstream at a high concentration.

According to the researchers, these receptors can be used to transport nanoparticles carrying different kinds of drugs and other materials—a feat that combines a versatile vehicle and an easily accessible passageway across cellular barriers.

To demonstrate how transport of Fc-targeted nanoparticles could impact the clinical space, the researchers focused on a diabetes treatment scenario, showing how oral delivery of insulin via these targeted nanoparticles could alter blood sugar levels in mice.

Insulin carried in nanoparticles decorated with Fc proteins reached the bloodstream more efficiently than those without the proteins. Moreover, the amount of insulin delivered was large enough to lower the mice’s blood sugar levels. Aside from insulin, the researchers note that the nanoparticles can be used to carry any kind of drug to treat many diseases.

“Being able to deliver nanomedicine orally would offer clinicians broad and novel ways to treat today’s many chronic diseases that require daily therapy, such as diabetes and cancer,” said Langer. “Imagine being able to take RNA or proteins orally; that would be paradigm shift.”

In terms of next steps, the researchers are working to enhance the nanoparticles’ drug-releasing abilities to prepare for future pre-clinical testing with insulin and other drugs. They also plan to design nanoparticles that can cross other barriers, such as the blood-brain barrier, which prevents many drugs from reaching the brain.

The Nov. 27, 2013 MIT news release by Anne Trafton on EurekAlert provides additional insight into the difficulties of getting nanoparticles past our digestive tracts (this is a bit repetitive but there’s enough new detail to make it worth my while to include it here),,

Several types of nanoparticles carrying chemotherapy drugs or short interfering RNA, which can turn off selected genes, are now in clinical trials to treat cancer and other diseases. These particles exploit the fact that tumors and other diseased tissues are surrounded by leaky blood vessels. After the particles are intravenously injected into patients, they seep through those leaky vessels and release their payload at the tumor site.

For nanoparticles to be taken orally, they need to be able to get through the intestinal lining, which is made of a layer of epithelial cells that join together to form impenetrable barriers called tight junctions.

“The key challenge is how to make a nanoparticle get through this barrier of cells. Whenever cells want to form a barrier, they make these attachments from cell to cell, analogous to a brick wall where the bricks are the cells and the mortar is the attachments, and nothing can penetrate that wall,” Farokhzad says.

Researchers have previously tried to break through this wall by temporarily disrupting the tight junctions, allowing drugs through. However, this approach can have unwanted side effects because when the barriers are broken, harmful bacteria can also get through.

To build nanoparticles that can selectively break through the barrier, the researchers took advantage of previous work that revealed how babies absorb antibodies from their mothers’ milk, boosting their own immune defenses. Those antibodies grab onto a cell surface receptor called the FcRN, granting them access through the cells of the intestinal lining into adjacent blood vessels.

The researchers coated their nanoparticles with Fc proteins — the part of the antibody that binds to the FcRN receptor, which is also found in adult intestinal cells. The nanoparticles, made of a biocompatible polymer called PLA-PEG, can carry a large drug payload, such as insulin, in their core.

After the particles are ingested, the Fc proteins grab on to the FcRN in the intestinal lining and gain entry, bringing the entire nanoparticle along with them.

“It illustrates a very general concept where we can use these receptors to traffic nanoparticles that could contain pretty much anything. Any molecule that has difficulty crossing the barrier could be loaded in the nanoparticle and trafficked across,” Karnik [Rohit Karnik, an MIT associate professor of mechanical engineering] says.

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

Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery by Eric M. Pridgen, Frank Alexis, Timothy T. Kuo, Etgar Levy-Nissenbaum, Rohit Karnik, Richard S. Blumberg, Robert Langer, and Omid C. Farokhzad.
Sci Transl Med 27 November 2013: Vol. 5, Issue 213, p. 213ra167 DOI: 10.1126/scitranslmed.3007049

This article is behind a paywall.

Doctor to patient: “Where would you like your carbon nanotubes implanted?”

A Nov. 3, 2013 news item on ScienceDaily offers some context, as well as, details for a sensing research project with medical applications being conducted at the Massachusetts Institute of Technology (MIT),

Nitric oxide (NO) is one of the most important signaling molecules in living cells, carrying messages within the brain and coordinating immune system functions. In many cancerous cells, levels are perturbed, but very little is known about how NO behaves in both healthy and cancerous cells.

“Nitric oxide has contradictory roles in cancer progression, and we need new tools in order to better understand it,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT. “Our work provides a new tool for measuring this important molecule, and potentially others, in the body itself and in real time.”

Led by postdoc Nicole Iverson, Strano’s lab has built a sensor that can monitor NO in living animals for more than a year. The sensors, described in the Nov. 3 issue of Nature Nanotechnology, can be implanted under the skin and used to monitor inflammation — a process that produces NO. This is the first demonstration that nanosensors could be used within the body for this extended period of time.

The Nov. 3, 2013 MIT news release (also on EurekAlert) written by Anne Trafton, which originated the news item, describes carbon nanotubes and how they are being used as sensing devices by the research team,

Carbon nanotubes — hollow, one-nanometer-thick cylinders made of pure carbon — have drawn great interest as sensors. Strano’s lab has recently developed carbon nanotube sensors for a variety of molecules, including hydrogen peroxide and toxic agents such as the nerve gas sarin. Such sensors take advantage of carbon nanotubes’ natural fluorescence, by coupling them to a molecule that binds to a specific target. When the target is bound, the tubes’ fluorescence brightens or dims.

Strano’s lab has previously shown that carbon nanotubes can detect NO if the tubes are wrapped in DNA with a particular sequence. In the new paper, the researchers modified the nanotubes to create two different types of sensors: one that can be injected into the bloodstream for short-term monitoring, and another that is embedded in a gel so it can be implanted long-term under the skin.

To make the particles injectable, Iverson attached PEG, a biocompatible polymer that inhibits particle-clumping in the bloodstream. She found that when injected into mice, the particles can flow through the lungs and heart without causing any damage. Most of the particles accumulate in the liver, where they can be used to monitor NO associated with inflammation.

“So far we have only looked at the liver, but we do see that it stays in the bloodstream and goes to kidneys. Potentially we could study all different areas of the body with this injectable nanoparticle,” Iverson says.

The longer-term sensor consists of nanotubes embedded in a gel made from alginate, a polymer found in algae. Once this gel is implanted under the skin of the mice, it stays in place and remains functional for 400 days; the researchers believe it could last even longer. This kind of sensor could be used to monitor cancer or other inflammatory diseases, or to detect immune reactions in patients with artificial hips or other implanted devices, according to the researchers.

Once the sensors are in the body, the researchers shine a near-infrared laser on them, producing a near-infrared fluorescent signal that can be read using an instrument that can tell the difference between nanotubes and other background fluorescence.

There is research into how the sensor could be adapted for use in diabetics, from the news release,

Iverson is now working on adapting the technology to detect glucose, by wrapping different kinds of molecules around the nanotubes.

Most diabetic patients must prick their fingers several times a day to take blood glucose readings. While there are electrochemical glucose sensors available that can be attached to the skin, those sensors last only a week at most, and there is a risk of infection because the electrode pierces the skin.

Furthermore, Strano says, the electrochemical sensor technology is not accurate enough to be incorporated into the kind of closed-loop monitoring system that scientists are now working toward. This type of system would consist of a sensor that offers real-time glucose monitoring, connected to an insulin pump that would deliver insulin when needed, with no need for finger pricking or insulin injection by the patient.

“The current thinking is that every part of the closed-loop system is in place except for an accurate and stable sensor. There is considerable opportunity to improve upon devices that are now on the market so that a complete system can be realized,” Strano says.

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

In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes by Nicole M. Iverson, Paul W. Barone, Mia Shandell, Laura J. Trudel, Selda Sen, Fatih Sen, Vsevolod Ivanov, Esha Atolia, Edgardo Farias, Thomas P. McNicholas, Nigel Reuel, Nicola M. A. Parry, Gerald N. Wogan & Michael S. Strano. Nature Nanotechnology (2013) doi:10.1038/nnano.2013.222 Published online 03 November 2013

There is a free preview of the article available via ReadCube Access otherwise this article is behind a paywall.

DNA tattoo patches

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]

NBD Nano startup company and the Namib desert beetle

In 2001, Andrew Parker and Chris Lawrence published an article in Nature magazine about work which has inspired a US startup company in 2012 to develop a water bottle that fills itself up with water by drawing moisture from the air. Parker’s and Lawrence’s article was titled Water capture by a desert beetle. Here’s the abstract (over 10 years later the article is still behind a paywall),

Some beetles in the Namib Desert collect drinking water from fog-laden wind on their backs1. We show here that these large droplets form by virtue of the insect’s bumpy surface, which consists of alternating hydrophobic, wax-coated and hydrophilic, non-waxy regions. The design of this fog-collecting structure can be reproduced cheaply on a commercial scale and may find application in water-trapping tent and building coverings, for example, or in water condensers and engines.

Some five years later, there was a June 15, 2006 news item on phys.org about the development of a new material based on the Namib desert beetle,

When that fog rolls in, the Namib Desert beetle is ready with a moisture-collection system exquisitely adapted to its desert habitat. Inspired by this dime-sized beetle, MIT [Massachusetts Institute of Technology] researchers have produced a new material that can capture and control tiny amounts of water.

The material combines a superhydrophobic (water-repelling) surface with superhydrophilic (water-attracting) bumps that trap water droplets and control water flow. The work was published in the online version of Nano Letters on Tuesday, May 2 [2006] {behind a paywall}.

Potential applications for the new material include harvesting water, making a lab on a chip (for diagnostics and DNA screening) and creating microfluidic devices and cooling devices, according to lead researchers Robert Cohen, the St. Laurent Professor of Chemical Engineering, and Michael Rubner, the TDK Professor of Polymer Materials Science and Engineering.

The MIT June 14, 2006 news release by Anne Trafton, which originated the news item about the new material, indicates there was some military interest,

The U.S. military has also expressed interest in using the material as a self-decontaminating surface that could channel and collect harmful substances.

The researchers got their inspiration after reading a 2001 article in Nature describing the Namib Desert beetle’s moisture-collection strategy. Scientists had already learned to copy the water-repellent lotus leaf, and the desert beetle shell seemed like another good candidate for “bio-mimicry.”

When fog blows horizontally across the surface of the beetle’s back, tiny water droplets, 15 to 20 microns, or millionths of a meter, in diameter, start to accumulate on top of bumps on its back.

The bumps, which attract water, are surrounded by waxy water-repelling channels. “That allows small amounts of moisture in the air to start to collect on the tops of the hydrophilic bumps, and it grows into bigger and bigger droplets,” Rubner said. “When it gets large, it overcomes the pinning force that holds it and rolls down into the beetle’s mouth for a fresh drink of water.”

To create a material with the same abilities, the researchers manipulated two characteristics — roughness and nanoporosity (spongelike capability on a nanometer, or billionths of a meter, scale).

By repeatedly dipping glass or plastic substrates into solutions of charged polymer chains dissolved in water, the researchers can control the surface texture of the material. Each time the substrate is dipped into solution, another layer of charged polymer coats the surface, adding texture and making the material more porous. Silica nanoparticles are then added to create an even rougher texture that helps trap water droplets.

The material is then coated with a Teflon-like substance, making it superhydrophobic. Once that water-repellent layer is laid down, layers of charged polymers and nanoparticles can be added in certain areas, using a properly formulated water/alcohol solvent mixture, thereby creating a superhydrophilic pattern. The researchers can manipulate the technique to create any kind of pattern they want.

The research is funded by the Defense Advanced Research Projects Agency and the National Science Foundation.

I’m not sure what happened with the military interest or the group working out of MIT in 2006 but on Nov. 23, 2012, BBC News online featured an article about a US startup company, NBD Nano, which aims to bring a self-filling water bottle based on Namib desert beetle to market,

NBD Nano, which consists of four recent university graduates and was formed in May, looked at the Namib Desert beetle that lives in a region that gets about half an inch of rainfall per year.

Using a similar approach, the firm wants to cover the surface of a bottle with hydrophilic (water-attracting) and hydrophobic (water-repellent) materials.

The work is still in its early stages, but it is the latest example of researchers looking at nature to find inspiration for sustainable technology.

“It was important to apply [biomimicry] to our design and we have developed a proof of concept and [are] currently creating our first fully-functional prototype,” Miguel Galvez, a co-founder, told the BBC.

“We think our initial prototype will collect anywhere from half a litre of water to three litres per hour, depending on local environments.”

According to the Nov. 25, 2012 article by Nancy Owano for phys.org, the company is at the prototype stage now,

NBD Nano plans to enter the worldwide marketplace between 2014 and 2015.

You can find out more about NBD Nano here.

Come, see my etchings … they detect poison gases

Inviting someone over to come see your etchings is an old seduction line made laughable through endless repetition. Maybe this latest innovation, will bring the line back into vogue. Researchers at the Massachusetts Institute of Technology (MIT) have devised a gas sensor that you can create/etch with a simple mechanical pencil and paper imprinted with gold electrodes.

The Oct. 9, 2012 news item on Nanowerk provides details,

Carbon nanotubes offer a powerful new way to detect harmful gases in the environment. However, the methods typically used to build carbon nanotube sensors are hazardous and not suited for large-scale production.

A new fabrication method created by MIT chemists — as simple as drawing a line on a sheet of paper — may overcome that obstacle. MIT postdoc Katherine Mirica has designed a new type of pencil lead in which graphite is replaced with a compressed powder of carbon nanotubes. The lead, which can be used with a regular mechanical pencil, can inscribe sensors on any paper surface.

The sensor, described in the journal Angewandte Chemie (“Mechanical Drawing of Gas Sensors on Paper”), detects minute amounts of ammonia gas, an industrial hazard. Timothy Swager, the John D. MacArthur Professor of Chemistry and leader of the research team, says the sensors could be adapted to detect nearly any type of gas.

The Oct. 9, 2012 MIT news release by Anne Trafton, which originated the news item, describes how the scientists developed this new fabrication system,

Swager and Mirica set out to create a solvent-free fabrication method based on paper. Inspired by pencils on her desk, Mirica had the idea to compress carbon nanotubes into a graphite-like material that could substitute for pencil lead.

To create sensors using their pencil, the researchers draw a line of carbon nanotubes on a sheet of paper imprinted with small electrodes made of gold. They then apply an electrical current and measure the current as it flows through the carbon nanotube strip, which acts as a resistor. If the current is altered, it means gas has bound to the carbon nanotubes.

The researchers tested their device on several different types of paper, and found that the best response came with sensors drawn on smoother papers. They also found that the sensors give consistent results even when the marks aren’t uniform.

Two major advantages of the technique are that it is inexpensive and the “pencil lead” is extremely stable, Swager says. “You can’t imagine a more stable formulation. The molecules are immobilized,” he says.

The new sensor could prove useful for a variety of applications, says Zhenan Bao, an associate professor of chemical engineering at Stanford University. “I can already think of many ways this technique can be extended to build carbon nanotube devices,” says Bao, who was not part of the research team. “Compared to other typical techniques, such as spin coating, dip coating or inkjet printing, I am impressed with the good reproducibility of sensing response they were able to get.”

It’s interesting but where carbon nanotubes are concerned I would like to know if they’ve considered safety issues. Given their similarity to asbestos fibres, it would seem researchers might want to indicate it’s safe to use carbon nanotubes in this new fabrication process.

Soldiers sniff overripe fruit

Technically speaking the soldiers are not sniffing the fruit, it’s the sensing technology developed at the Massachusetts Institute of Technology’s Institute for Soldier Nanotechnologies which is doing the ‘sniffing’. From the April 30, 2012 news item on Nanowerk (I have removed some links),

Every year, U.S. supermarkets lose roughly 10 percent of their fruits and vegetables to spoilage, according to the Department of Agriculture. To help combat those losses, MIT chemistry professor Timothy Swager and his students have built a new sensor that could help grocers and food distributors better monitor their produce.

The new sensors, described in the journal Angewandte Chemie (“Selective Detection of Ethylene Gas Using Carbon Nanotube-based Devices: Utility in Determination of Fruit Ripeness”), can detect tiny amounts of ethylene, a gas that promotes ripening in plants. Swager envisions the inexpensive sensors attached to cardboard boxes of produce and scanned with a handheld device that would reveal the contents’ ripeness.

Detecting gases to monitor the food supply is a new area of interest for Swager, whose previous research has focused on sensors to detect explosives or chemical and biological warfare agents.

Here’s how the technology works (from the April 30, 2012 news release by Anne Trafton for MIT News),

Funded by the U.S. Army Office of Research through MIT’s Institute for Soldier Nanotechnologies, the MIT team built a sensor consisting of an array of tens of thousands of carbon nanotubes: sheets of carbon atoms rolled into cylinders that act as “superhighways” for electron flow.

To modify the tubes to detect ethylene gas, the researchers added copper atoms, which serve as “speed bumps” to slow the flowing electrons. “Anytime you put something on these nanotubes, you’re making speed bumps, because you’re taking this perfect, pristine system and you’re putting something on it,” Swager says.

Copper atoms slow the electrons a little bit, but when ethylene is present, it binds to the copper atoms and slows the electrons even more. By measuring how much the electrons slow down — a property also known as resistance — the researchers can determine how much ethylene is present.

To make the device even more sensitive, the researchers added tiny beads of polystyrene, which absorbs ethylene and concentrates it near the carbon nanotubes. With their latest version, the researchers can detect concentrations of ethylene as low as 0.5 parts per million. The concentration required for fruit ripening is usually between 0.1 and one part per million.

The researchers tested their sensors on several types of fruit — banana, avocado, apple, pear and orange — and were able to accurately measure their ripeness by detecting how much ethylene the fruits secreted.

It looks like the technology will be commercialized in the not too distant future (from the Trafton news release) here’s why,

John Saffell, the technical director at Alphasense, a company that develops sensors, describes the MIT team’s approach as rigorous and focused. “This sensor, if designed and implemented correctly, could significantly reduce the level of fruit spoilage during shipping,” he says.

“At any given time, there are thousands of cargo containers on the seas, transporting fruit and hoping that they arrive at their destination with the correct degree of ripeness,” adds Saffell, who was not involved in this research. “Expensive analytical systems can monitor ethylene generation, but in the cost-sensitive shipping business, they are not economically viable for most of shipped fruit.”

Swager has filed for a patent on the technology and hopes to start a company to commercialize the sensors. In future work, he plans to add a radio-frequency identification (RFID) chip to the sensor so it can communicate wirelessly with a handheld device that would display ethylene levels. The system would be extremely cheap — about 25 cents for the carbon nanotube sensor plus another 75 cents for the RFID chip, Swager estimates.

“This could be done with absolutely dirt-cheap electronics, with almost no power,” he says.

I should mention that a couple of students were part of the MIT research team with Birgit Esser being the lead author and Jan Schnorr also contributing to the paper in Angewandte Chemie.

Never bleed again? New nanoscale bio coating stops bleeding in seconds

It’s not quite instantaneous but the new nanoscale biological coating devised by MIT (Massachusetts Institute of Technology) engineers at their Institute of Soldier Nanotechnologies cuts bleeding time to less than 1/2 of what it was (from 150 seconds to 60 seconds) in animal tests. The Jan. 10, 2012 news item on Nanowerk provides more detail,

MIT engineers have developed a nanoscale biological coating that can halt bleeding nearly instantaneously, an advance that could dramatically improve survival rates for soldiers injured in battle.

The researchers, led by Paula Hammond and funded by MIT’s Institute of Soldier Nanotechnologies and a Denmark-based company, Ferrosan Medical Devices A/S, created a spray coating that includes thrombin, a clotting agent found in blood. Sponges coated with this material can be stored stably and easily carried by soldiers or medical personnel.

The Jan. 10, 2012 news release by Anne Trafton for MIT notes,

Uncontrolled bleeding is the leading cause of trauma death on the battlefield. Traditional methods to halt bleeding, such as tourniquets, are not suitable for the neck and many other parts of the body. In recent years, researchers have tried alternative approaches, all of which have some disadvantages. Fibrin dressings and glues have a short shelf life and can cause an adverse immune response, and zeolite powders are difficult to apply under windy conditions and can cause severe burns. Another option is bandages made of chitosan, a derivative of the primary structural material of shellfish exoskeletons. Those bandages have had some success but can be difficult to mold to fit complex wounds.

Many civilian hospitals use a highly absorbent gelatin sponge produced by Ferrosan to stop bleeding. However, those sponges need to be soaked in liquid thrombin just before application to the wound, making them impractical for battlefield use. Hammond’s team came up with the idea to coat the sponges with a blood-clotting agent in advance, so they would be ready when needed, for either military or civilian use.

To do that, the researchers developed a nanoscale biological coating that consists of two alternating layers sprayed onto a material, such as the sponges used in this study. The researchers discovered that layers of thrombin, a natural clotting protein, and tannic acid, a small molecule found naturally in tea, yield a film containing large amounts of functional thrombin. Both materials are already approved by the U.S. Food and Drug Administration, which could help with the approval process for a commercialized version of the sponges, Shukla [Anita Shukla PhD ’11] says.

A key advantage of the spray method is that it allows a large amount of thrombin to be packed into the sponges, coating even the interior fibers, says David King, a trauma surgeon and instructor in surgery at Massachusetts General Hospital who was not involved in this research.

“All of the existing hemostatic materials suffer from the same limitation, which is being able to deliver a dense enough package of hemostatic material to the bleeding site. That’s why this new material is exciting,” says King, also an Army reservist who has served in Afghanistan as chief of trauma surgery.

Very exciting stuff but no word as to when it might reach the marketplace. A patent application has been filed but it doesn’t seem that any human clinical trials have been held yet. As best I can determine, all of the testing done (at Ferrosan) so far has been on animals.

I did check out the Ferrosan website and found this on their About page,

Ferrosan is an international consumer health company with strong market positions and a solid financial performance.

We strive for optimal development by selectively aiming for position as a leader through organic as well as M&A-driven growth.

In order to accomplish our objectives each employee must deliver upon Ferrosan’s values:

  • Get things done
  • Exceed expectations
  • Appreciate individual differences
  • Enjoy and have fun

The foundation of our future success is based on each employee’s ability to make a difference.

Ferrosan is a well established pharmaceutical company with a great heritage. In 2010, we celebrated the company’s 90th anniversary.

A nanocrystalline solar cell; nano haiku; and more courtesy of the NISE Net

June’s Nanoscale Informal Science Education (NISE) Network newsletter features a 2009 video, Nanotechnology brings us Delicious Nanocrystalline solar cells,  which was entered for the American Chemical Society’s 2009 Nanotation Nanotube contest.Who knew you could use donuts and tea to make a solar cell?

ETA June 20, 2011: Dexter Johnson in a June 17, 2011 posting on his Nanoclast blog points out that the science in this video is not of the best calibre.

On another note entirely, an April 22, 2010 posting from Clark Miller on the NISE Net blog focuses on bio-non-bio interfaces. Excerpted from Miller’s posting,

What would it mean if biological and non-biological systems were not just fully connectable but fully interchangeable? That’s one of the questions that nanotechnology poses for us. More than any other field of scientific inquiry, nanotechnology operates at the basic scales of biology. DNA, for example, has a rough width of 2.5 nm. Viruses are roughly 20 to 250 nm. A bacteria is roughly 1000 nm. So, nanotechnology spans from the scale of individual biological molecules through the scale of simple biological systems to the scale of living cells.

Miller certainly poses an interesting question especially in light of work which could conceivably lead (or perhaps already has led) to interchangeable biological and nonbiological systems,

For example, researchers at the University of Wisconsin-Madison have developed a new sensor for viruses that works through a combination of nanotechnology elements. The base of the sensor is a flat basin filled with liquid crystals (these are crystal molecules that behave like a liquid and form the core materials used in computer and flat-screen TVs). Within the basin are a series of parallel ridges approximately 5 nm on each side. These ridges help orient the liquid crystals so that they line up in parallel to the ridges and therefore exhibit a constant color across the entire basin. Finally, set into the ridges are a series of antibody particles for a specific virus. Once built, the sensor is exposed to material that might contain the virus in question. If the virus is present, it will bind to the antibody and, when it does, disturb the arrangement of the liquid crystals. When the liquid crystals are disturbed, the sensor changes color, signaling a positive match.

I haven’t seen any public engagement exercises that raise the issue in quite that way. At this point, it seems to be the province of science fiction.

Before I finish this posting with the June 2011 Nano Haiku, I’ll give you a little information about the article by Anne Trafton that inspired it, Finding a needle in a haystack: New sensor developed by MIT chemical engineers can detect tiny traces of explosives,

MIT [Massachusetts Institute of Technology] researchers have created a new detector so sensitive it can pick up a single molecule of an explosive such as TNT.

To create the sensors, chemical engineers led by Michael Strano coated carbon nanotubes — hollow, one-atom-thick cylinders made of pure carbon — with protein fragments normally found in bee venom. This is the first time those proteins have been shown to react to explosives, specifically a class known as nitro-aromatic compounds that includes TNT.

And now the Nano Haiku,

Bee venom and nanotubes
Raise nano red flags
For super small explosives

by Vrylena Olney of the Museum of Science, Boston.