Tag Archives: US

RNA interference: a Tekmira deal and a new technique births Solstice Biologics

I have two news items concerning ribonucleic acid interference (RNAi). The first item features Tekmira Pharmaceuticals Corporation (a Canadian company located in the Vancouver area) and a licencing deal with Dicerna Pharmaceuticals (Massachusetts, US), according to a Nov. 18, 2014 news item on Azonano,

Tekmira Pharmaceuticals Corporation a leading developer of RNA interference (RNAi) therapeutics, today announces a licensing and collaboration agreement with Dicerna Pharmaceuticals, Inc. Tekmira has licensed its proprietary lipid nanoparticle (LNP) delivery technology for exclusive use in Dicerna’s primary hyperoxaluria type 1 (PH1) development program.

Under the agreement, Dicerna will pay Tekmira $2.5 million upfront and payments of $22 million in aggregate development milestones, plus a mid-single-digit royalty on future PH1 sales. This new partnership also includes a supply agreement with Tekmira providing clinical drug supply and regulatory support in the rapid advancement of the product candidate.

The agreement announced today follows the successful testing and demonstration of positive results combining Tekmira’s LNP technology with DCR-PH1 in pre-clinical animal models.

I don’t entirely understand what they mean by “pre-clinical animal models” as I’ve not noticed the term “pre-clinical” applied to animal testing before this. It’s possible they mean they’ve run tests on animals (in vivo) and are now proceeding to human clinical trials or it could mean they’ve run in silico (computer modeling) or in vitro (test tube/test slide) tests and are now proceeding to animal tests. If anyone should have some insights, please do share them with me in the comments section.

A Nov. 17, 2014 Tekmira news release, which originated the news item, describes the deal in more detail,

Dicerna will use Tekmira’s third generation LNP technology for delivery of DCR-PH1, Dicerna’s Dicer substrate RNA (DsiRNA) molecule, for the treatment of PH1, a rare, inherited liver disorder that often results in kidney failure and for which there are no approved therapies.

“This new agreement validates our leadership position in RNAi delivery with LNP technology, and it underscores the significant value we can bring to partners who leverage our technology. Our LNP technology is enabling the most advanced applications of RNAi therapeutics in the clinic, and it continues to do so. We are excited to be working with Dicerna to be able to advance a needed therapeutic for the treatment of PH1,” said Dr. Mark J. Murray, Tekmira’s President and CEO.

“As a core pillar of our business strategy, we continue to engage in partnerships where our technology improves the risk profile and accelerates the development programs of our collaborators and provides meaningful non-dilutive financing to TKMR,” added Dr. Murray.

“Dicerna is focused on realizing the full clinical potential of our proprietary pipeline of highly targeted RNAi therapies by applying proven technologies,” said Douglas Fambrough, Ph.D., Chief Executive Officer of Dicerna. “By drawing on Tekmira’s extensive and deep experience with lipid nanoparticle delivery to the liver, the agreement will streamline the development path for DCR-PH1. We look forward to initiating Phase 1 trials of DCR-PH1 in 2015, aiming to fill a high unmet medical need for patients with PH1.”

The news release also provides a high level description of the various technologies being researched and brought to market and a bit more information about the liver disorder being addressed by this research,

About RNAi

RNAi therapeutics have the potential to treat a number of human diseases by “silencing” disease-causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi trigger molecules often require delivery technology to be effective as therapeutics.

AboutTekmira’s LNP Technology

Tekmira believes its LNP technology represents the most widely adopted delivery technology for the systemic delivery of RNAi triggers. Tekmira’s LNP platform is being utilized in multiple clinical trials by Tekmira and its partners. Tekmira’s LNP technology (formerly referred to as stable nucleic acid-lipid particles, or SNALP) encapsulates RNAi triggers with high efficiency in uniform lipid nanoparticles that are effective in delivering these therapeutic compounds to disease sites. Tekmira’s LNP formulations are manufactured by a proprietary method which is robust, scalable and highly reproducible, and LNP-based products have been reviewed by multiple regulatory agencies for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.

About Primary Hyperoxaluria Type 1 ( PH1)

PH1 is a rare, inherited liver disorder that often results in severe damage to the kidneys. The disease can be fatal unless the patient undergoes a liver-kidney transplant, a major surgical procedure that is often difficult to perform due to the lack of donors and the threat of organ rejection. In the event of a successful transplant, the patient must live the rest of his or her life on immunosuppressant drugs, which have substantial associated risks. Currently, there are no FDA approved treatments for PH1.

PH1 is characterized by a genetic deficiency of the liver enzyme alanine:glyoxalate-aminotransferase (AGT), which is encoded by the AGXT gene. AGT deficiency induces overproduction of oxalate by the liver, resulting in the formation of crystals of calcium oxalate in the kidneys. Oxalate crystal formation often leads to chronic and painful cases of kidney stones and subsequent fibrosis (scarring), which is known as nephrocalcinosis. Many patients progress to end-stage renal disease (ESRD) and require dialysis or transplant. Aside from having to endure frequent dialysis, PH1 patients with ESRD may experience a build-up of oxalate in the bone, skin, heart and retina, with concomitant debilitating complications. While the true prevalence of primary hyperoxaluria is unknown, it is estimated to be one to three cases per one million people.1 Fifty percent of patients with PH1 reach ESRD by their mid-30s.2

About DCR-PH1

Dicerna is developing DCR-PH1, which is in preclinical development, for the treatment of PH1. DCR-PH1 is engineered to address the pathology of PH1 by targeting and destroying the messenger RNA (mRNA) produced by HAO1, a gene implicated in the pathogenesis of PH1. HAO1 encodes glycolate oxidase, a protein involved in producing oxalate. By reducing oxalate production, this approach is designed to prevent the complications of PH1. In preclinical studies, DCR-PH1 has been shown to induce potent and long-term inhibition of HAO1 and to significantly reduce levels of urinary oxalate, while demonstrating long-term efficacy and tolerability in animal models of PH1.

About Dicerna’s Dicer Substrate Technology

Dicerna’s proprietary RNAi molecules are known as Dicer substrates, or DsiRNAs, so called because they are processed by the Dicer enzyme, which is the initiation point for RNAi in the human cell cytoplasm. Dicerna’s discovery approach is believed to maximize RNAi potency because the DsiRNAs are structured to be ideal for processing by Dicer. Dicer processing enables the preferential use of the correct RNA strand of the DsiRNA, which may increase the efficacy of the RNAi mechanism, as well as the potency of the DsiRNA molecules relative to other molecules used to induce RNAi.

You can find more information about Tekmira here and about Dicerna here. I mentioned Tekmira previously in a Sept. 28, 2014 post about Ebola and treatments.

Further south at the University of California at San Diego (UCSD), researcher and founder of Solstice Biologics, Dr Steven Dowdy has developed and patented a new technique for delivering RNAi drugs into cells according to a Nov. 18, 2014 news item on Azonano,

Small pieces of synthetic RNA trigger a RNA interference (RNAi) response that holds great therapeutic potential to treat a number of diseases, especially cancer and pandemic viruses. The problem is delivery — it is extremely difficult to get RNAi drugs inside the cells in which they are needed. To overcome this hurdle, researchers at University of California, San Diego School of Medicine have developed a way to chemically disguise RNAi drugs so that they are able to enter cells. Once inside, cellular machinery converts these disguised drug precursors — called siRNNs — into active RNAi drugs. …

A Nov. 17, 2014 UCSD news release (also on EurekAlert) by Heather Buschman, which originated the news item, describes the issues with delivering RNAi drugs to cells and the new technique,

“Many current approaches use nanoparticles to deliver RNAi drugs into cells,” said Steven F. Dowdy, PhD, professor in the Department of Cellular and Molecular Medicine and the study’s principal investigator. “While nanotechnology protects the RNAi drug, from a molecular perspective nanoparticles are huge, some 5,000 times larger than the RNAi drug itself. Think of delivering a package into your house by having an 18-wheeler truck drive it through your living room wall — that’s nanoparticles carrying standard RNAi drugs. Now think of a package being slipped through the mail slot — that’s siRNNs.”

The beauty of RNAi is that it selectively blocks production of target proteins in a cell, a finding that garnered a Nobel Prize in 2006. While this is a normal process that all cells use, researchers have taken advantage of RNAi to inhibit specific proteins that cause disease when overproduced or mutated, such as in cancer. First, researchers generate RNAi drugs with a sequence that corresponds to the gene blueprint for the disease protein and then delivers them into cells. Once inside the cell, the RNAi drug is loaded into an enzyme that specifically slices the messenger RNA encoding the target protein in half. This way, no protein is produced.

As cancer and viral genes mutate, RNAi drugs can be easily evolved to target them. This allows RNAi therapy to keep pace with the genetics of the disease — something that no other type of therapy can do. Unfortunately, due to their size and negatively charged chemical groups (phosphates) on their backbone, RNAi drugs are repelled by the cellular membrane and cannot be delivered into cells without a special delivery agent.

It took Dowdy and his team, including Bryan Meade, PhD, Khirud Gogoi, PhD, and Alexander S. Hamil, eight years to find a way to mask RNAi’s negative phosphates in such a way that gets them into cells, but is still capable of inducing an RNAi response once inside.

In the end, the team added a chemical tag called a phosphotriester group. The phosphotriester neutralizes and protects the RNA backbone — converting the ribonucleic acid (RNA) to ribonucleic neutral (RNN), and thus giving the name siRNN. The neutral (uncharged) nature of siRNNs allows them to pass into the cell much more efficiently. Once inside the cell, enzymes cleave off the neutral phosphotriester group to expose a charged RNAi drug that shuts down production of the target disease protein. siRNNs represent a transformational next-generation RNAi drug.

“siRNNs are precursor drugs, or prodrugs, with no activity. It’s like having a tool still in the box, it won’t work until you take it out,” Dowdy said. “Only when the packaging — the phosphotriester groups — is removed inside the cells do you have an active tool or RNAi drug.”

The findings held up in a mouse model, too. There, Dowdy’s team found that siRNNs were significantly more effective at blocking target protein production than typical RNAi drugs — demonstrating that once siRNNs get inside a cell they can do a better job.

“There remains a lot of work ahead to get this into the clinics. But, in theory, the therapeutic potential of siRNNs is endless,” Dowdy said. “Particularly for cancer, viral infections and genetic diseases.”

The siRNN technology forms the basis for Solstice Biologics, a biotech company in La Jolla, Calif. that is now taking the technique to the next level. Dowdy is a co-founder of Solstice Biologics and serves as a Board Director.

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

Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications by Bryan R Meade, Khirud Gogoi, Alexander S Hamil, Caroline Palm-Apergi, Arjen van den Berg, Jonathan C Hagopian, Aaron D Springer, Akiko Eguchi, Apollo D Kacsinta, Connor F Dowdy, Asaf Presente, Peter Lönn, Manuel Kaulich, Naohisa Yoshioka, Edwige Gros, Xian-Shu Cui, & Steven F Dowdy. Nature Biotechnology (2014) doi:10.1038/nbt.3078 Published online 17 November 2014

This paper is behind a paywall.

I have not been able to locate a website for Solstice Biologics but did find a rather curious item about Dr. Dowdy and a shooting incident last year. From a Sept. 18, 2013 news article by Kat Robinson for thewire.sheknows.com,

A wealthy San Diego community is shaken after a man opens fire on his former neighborhood early Wednesday morning. Police say Hans Petersen, a 48-year-old man, is the prime suspect in the shooting of Steven Dowdy and Michael Fletcher.

There’s also a Nov. 8, 2013 article about the incident by Lucas Laursen for Nature magazine,

On September 18 [2013], former Traversa Therapeutics CEO Hans Petersen went on a shooting spree. One of two people wounded was molecular biologist Steven Dowdy, a professor at University of California San Diego (UCSD) School of Medicine, in La Jolla, and cofounder of Traversa, according to a San Diego police report.…

The rest of the article is behind a paywall.

India, Lockheed Martin, and canal-top solar power plants

Apparently the state of Gujarat (India) has inspired at least one other state, Punjab, to build (they hope) a network of photovoltaic (solar energy) plants over top of their canal system (from a Nov. 16, 2014 article by Mridul Chadha for cleantechnica.com),

India’s northern state of Punjab plans to set up 1,000 MW of solar PV projects to cover several kilometres of canals over the next three years. The state government has announced a target to cover 5,000 km of canals across the state. Through this program, the government hopes to generate 15% of the state’s total electricity demand.

Understandably, the construction of canal-top power plants is technically and structurally very different from rooftop or ground-based solar PV projects. The mounting structures for the solar PV modules cannot be heavy, as it could adversely impact the structural integrity of the canal itself. The structures should be easy to work with, as they are to be set up over a slope.

This is where the Punjab government has asked Lockheed Martin for help. The US-based company has entered into an agreement with the Punjab government to develop lightweight mounting structures for solar panels using nanotechnology.

Canal and rooftop solar power projects are the only viable options for Punjab as it is an agricultural state and land availability for large-scale ground-mounted projects remains an issue. As a result, the state government has a relatively lower (compared to other states) capacity addition target of 2 GW.

There’s more about the Punjab and current plans to increase its investment in solar photovoltaics in the article.

Here’s an image of a canal-top solar plant near Kadi (Gujarat),

Canal_Top_Solar_Power_PlantImage Credit: Hitesh vip | CC BY-SA 3.0

A Nov. 15, 2014 news item by Kamya Kandhar for efytimes.com provides a few more details about this Memorandum of Understanding (MOU),

Punjab government had announced its tie up with U.S. aerospace giant Lockheed Martin to expand the solar power generation and overcome power problems in the State. As per the agreement, the state will put in 1,000 MW solar power within the next three years. Lockheed Martin has agreed to provide plastic structures for solar panels on canals by using nano technology.

While commenting upon the agreement, a spokesperson said, “The company would also provide state-of-the-art technology to convert paddy straw into energy, solving the lingering problem of paddy straw burning in the state. The Punjab government and Lockheed Martin would ink a MoU in this regard [on Friday, Nov. 14, 2014].”

The decision was taken during a meeting between three-member team from Lockheed Martin, involving the CEO Phil Shaw, Chief Innovation Officer Tushar Shah and Regional Director Jagmohan Singh along with Punjab Non-Conventional Energy Minister Bikram Singh Majithia and other senior Punjab officials.

As for paddy straw and its conversion into energy, there’s this from a Nov. 14, 2014 news item on India West.com,

Shaw [CEO Phil Shaw] said Lockheed has come out with waste-to-energy conversion solutions with successful conversion of waste products to electricity, heat and fuel by using gasification processes. He said it was an environmentally friendly green recycling technology, which requires little space and the plants are fully automated.

Getting back to the nanotechnology, I was not able to track down any information about nanotechnology-enabled plastics and Lockheed Martin. But, there is a Dec. 11, 2013 interview with Travis Earles, Lockheed Martin Advanced materials and nanotechnology innovation executive and policy leader, written up by Kris Walker for Azonano. Note: this is a general interview and focuses largely on applications for carbon nanotubes and graphene.

Nano and stem cell differentiation at Rutgers University (US)

A Nov. 14, 2014 news item on Azonano features a nanoparticle-based platform for differentiating stem cells,

Rutgers University Chemistry Associate Professor Ki-Bum Lee has developed patent-pending technology that may overcome one of the critical barriers to harnessing the full therapeutic potential of stem cells.

A Nov. 1, 2104 Rutgers University news release, which originated the news item, describes the challenge in more detail,

One of the major challenges facing researchers interested in regenerating cells and growing new tissue to treat debilitating injuries and diseases such as Parkinson’s disease, heart disease, and spinal cord trauma, is creating an easy, effective, and non-toxic methodology to control differentiation into specific cell lineages. Lee and colleagues at Rutgers and Kyoto University in Japan have invented a platform they call NanoScript, an important breakthrough for researchers in the area of gene expression. Gene expression is the way information encoded in a gene is used to direct the assembly of a protein molecule, which is integral to the process of tissue development through stem cell therapeutics.

Stem cells hold great promise for a wide range of medical therapeutics as they have the ability to grow tissue throughout the body. In many tissues, stem cells have an almost limitless ability to divide and replenish other cells, serving as an internal repair system.

Transcription factor (TF) proteins are master regulators of gene expression. TF proteins play a pivotal role in regulating stem cell differentiation. Although some have tried to make synthetic molecules that perform the functions of natural transcription factors, NanoScript is the first nanomaterial TF protein that can interact with endogenous DNA. …

“Our motivation was to develop a highly robust, efficient nanoparticle-based platform that can regulate gene expression and eventually stem cell differentiation,” said Lee, who leads a Rutgers research group primarily focused on developing and integrating nanotechnology with chemical biology to modulate signaling pathways in cancer and stem cells. “Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential to do exactly that. The field of stem cell biology now has another platform to regulate differentiation while the field of nanotechnology has demonstrated for the first time that we can regulate gene expression at the transcriptional level.”

Here’s an image illustrating NanoScript and gold nanoparticles,

Courtesy Rutgers University

Courtesy Rutgers University

The news release goes on to describe the platform’s use of gold nanoparticles,

NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles.

“NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by up to 30-fold,” said Sahishnu Patel, Rutgers Chemistry graduate student and co-author of the ACS Nano publication. “NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner.”

Lee said the next step for his research is to study what happens to the gold nanoparticles after NanoScript is utilized, to ensure no toxic effects arise, and to ensure the effectiveness of NanoScript over long periods of time.

“Due to the unique tunable properties of NanoScript, we are highly confident this platform not only will serve as a desirable alternative to conventional gene-regulating methods,” Lee said, “but also has direct employment for applications involving gene manipulation such as stem cell differentiation, cancer therapy, and cellular reprogramming. Our research will continue to evaluate the long-term implications for the technology.”

Lee, originally from South Korea, joined the Rutgers faculty in 2008 and has earned many honors including the NIH Director’s New Innovator Award. Lee received his Ph.D. in Chemistry from Northwestern University where he studied with Professor Chad. A. Mirkin, a pioneer in the coupling of nanotechnology and biomolecules. Lee completed his postdoctoral training at The Scripps Research Institute with Professor Peter G. Schultz. Lee has served as a Visiting Scholar at both Princeton University and UCLA Medical School.

The primary interest of Lee’s group is to develop and integrate nanotechnologies and chemical functional genomics to modulate signaling pathways in mammalian cells towards specific cell lineages or behaviors. He has published more than 50 articles and filed for 17 corresponding patents.

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

NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation by Sahishnu Patel, Dongju Jung, Perry T. Yin, Peter Carlton, Makoto Yamamoto, Toshikazu Bando, Hiroshi Sugiyama, and Ki-Bum Lee. ACS Nano, 2014, 8 (9), pp 8959–8967 DOI: 10.1021/nn501589f Publication Date (Web): August 18, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

Killing mosquitos and other pests with genetics-based technology

Having supplied more than one tasty meal for mosquitos (or, as some prefer, mosquitoes), I am not their friend but couldn’t help but wonder about unintended consequences (as per Max Weber) on reading about a new patent awarded to Kansas State University (from a Nov. 12, 2014 news item on Nanowerk),

Kansas State University researchers have developed a patented method of keeping mosquitoes and other insect pests at bay.

U.S. Patent 8,841,272, “Double-Stranded RNA-Based Nanoparticles for Insect Gene Silencing,” was recently awarded to the Kansas State University Research Foundation, a nonprofit corporation responsible for managing technology transfer activities at the university. The patent covers microscopic, genetics-based technology that can help safely kill mosquitos and other insect pests.

A Nov. 12, 2014 Kansas State University news release, which originated the news item, provides more detail about the research,

Kun Yan Zhu, professor of entomology; Xin Zhang, research associate in the Division of Biology; and Jianzhen Zhang, visiting scientist from Shanxi University in China, developed the technology: nanoparticles comprised of a nontoxic, biodegradable polymer matrix and insect derived double-stranded ribonucleic acid, or dsRNA. Double-stranded RNA is a synthesized molecule that can trigger a biological process known as RNA interference, or RNAi, to destroy the genetic code of an insect in a specific DNA sequence.

The technology is expected to have great potential for safe and effective control of insect pests, Zhu said.

“For example, we can buy cockroach bait that contains a toxic substance to kill cockroaches. However, the bait could potentially harm whatever else ingests it,” Zhu said. “If we can incorporate dsRNA specifically targeting a cockroach gene in the bait rather than a toxic substance, the bait would not harm other organisms, such as pets, because the dsRNA is designed to specifically disable the function of the cockroach gene.”

Researchers developed the technology while looking at how to disable gene functions in mosquito larvae. After testing a series of unsuccessful genetic techniques, the team turned to a nanoparticle-based approach.

Once ingested, the nanoparticles act as a Trojan horse, releasing the loosely bound dsRNA into the insect gut. The dsRNA then triggers a genetic chain reaction that destroys specific messenger RNA, or mRNA, in the developing insects. Messenger RNA carries important genetic information.

In the studies on mosquito larvae, researchers designed dsRNA to target the mRNA encoding the enzymes that help mosquitoes produce chitin, the main component in the hard exoskeleton of insects, crustaceans and arachnids.

Researchers found that the developing mosquitoes produced less chitin. As a result, the mosquitoes were more prone to insecticides as they no longer had a sufficient amount of chitin for a normal functioning protective shell. If the production of chitin can be further reduced, the insects can be killed without using any toxic insecticides.

While mosquitos were the primary insect for which the nanoparticle-based method was developed, the technology can be applied to other insect pests, Zhu said.

“Our dsRNA molecules were designed based on specific gene sequences of the mosquito,” Zhu said. “You can design species-specific dsRNA for the same or different genes for other insect pests. When you make baits containing gene-specific nanoparticles, you may be able to kill the insects through the RNAi pathway. We see this having really broad applications for insect pest management.”

The patent is currently available to license through the Kansas State University Institute for Commercialization, which licenses the university’s intellectual property. The Institute for Commercialization can be contacted at 785-532-3900 and [email protected]

Eight U.S. patents have been awarded to the Kansas State University Research Foundation in 2014 for inventions by Kansas State University researchers.

Here’s an image of the ‘Trojan horse’ nanoparticles,

The nanoparticles, pictured as gold colored, are less than 100 nanometers in diameter. photo credit: bogdog Dan via photopincc

The nanoparticles, pictured as gold colored, are less than 100 nanometers in diameter. photo credit: bogdog Dan via photopincc

My guess is that the photographer has added some colour such as the gold and the pink to enhance the image as otherwise this would be a symphony of grey tones.

So, if this material will lead to weakened chitin such that pesticides and insecticides are more effective, does this mean that something else in the food chain will suffer because it no longer has mosquitos and other pests to munch on?

One last note, usually my ‘mosquito’ pieces concern malaria and the most recent of those was a Sept. 4, 2014 posting about a possible malaria vaccine being developed at the University of Connecticut.

Super-capacitors on automobiles

Queensland University of Technology* (QUT; Australia) researchers are hopeful they can adapt supercapacitors in the form of a fine film tor use in electric vehicles making them more energy-efficient. From a Nov. 6, 2014 news item on ScienceDaily,

A car powered by its own body panels could soon be driving on our roads after a breakthrough in nanotechnology research by a QUT team.

Researchers have developed lightweight “supercapacitors” that can be combined with regular batteries to dramatically boost the power of an electric car.

The discovery was made by Postdoctoral Research Fellow Dr Jinzhang Liu, Professor Nunzio Motta and PhD researcher Marco Notarianni, from QUT’s Science and Engineering Faculty — Institute for Future Environments, and PhD researcher Francesca Mirri and Professor Matteo Pasquali, from Rice University in Houston, in the United States.

A Nov. 6, 2014 QUT news release, which originated the news item, describes supercapacitors, the research, and the need for this research in more detail,

The supercapacitors – a “sandwich” of electrolyte between two all-carbon electrodes – were made into a thin and extremely strong film with a high power density.

The film could be embedded in a car’s body panels, roof, doors, bonnet and floor – storing enough energy to turbocharge an electric car’s battery in just a few minutes.

“Vehicles need an extra energy spurt for acceleration, and this is where supercapacitors come in. They hold a limited amount of charge, but they are able to deliver it very quickly, making them the perfect complement to mass-storage batteries,” he said.

“Supercapacitors offer a high power output in a short time, meaning a faster acceleration rate of the car and a charging time of just a few minutes, compared to several hours for a standard electric car battery.”

Dr Liu said currently the “energy density” of a supercapacitor is lower than a standard lithium ion (Li-Ion) battery, but its “high power density”, or ability to release power in a short time, is “far beyond” a conventional battery.

“Supercapacitors are presently combined with standard Li-Ion batteries to power electric cars, with a substantial weight reduction and increase in performance,” he said.

“In the future, it is hoped the supercapacitor will be developed to store more energy than a Li-Ion battery while retaining the ability to release its energy up to 10 times faster – meaning the car could be entirely powered by the supercapacitors in its body panels.

“After one full charge this car should be able to run up to 500km – similar to a petrol-powered car and more than double the current limit of an electric car.”

Dr Liu said the technology would also potentially be used for rapid charges of other battery-powered devices.

“For example, by putting the film on the back of a smart phone to charge it extremely quickly,” he said.

The discovery may be a game-changer for the automotive industry, with significant impacts on financial, as well as environmental, factors.

“We are using cheap carbon materials to make supercapacitors and the price of industry scale production will be low,” Professor Motta said.

“The price of Li-Ion batteries cannot decrease a lot because the price of Lithium remains high. This technique does not rely on metals and other toxic materials either, so it is environmentally friendly if it needs to be disposed of.”

A Nov. 10, 2014 news item on Azonano describes the Rice University (Texas, US) contribution to this work,

Rice University scientist Matteo Pasquali and his team contributed to two new papers that suggest the nano-infused body of a car may someday power the car itself.

Rice supplied high-performance carbon nanotube films and input on the device design to scientists at the Queensland University of Technology in Australia for the creation of lightweight films containing supercapacitors that charge quickly and store energy. The inventors hope to use the films as part of composite car doors, fenders, roofs and other body panels to significantly boost the power of electric vehicles.

A Nov. 7, 2014 Rice University news release, which originated the news item, offers a few technical details about the film being proposed for use as a supercapacitor on car panels,

Researchers in the Queensland lab of scientist Nunzio Motta combined exfoliated graphene and entangled multiwalled carbon nanotubes combined with plastic, paper and a gelled electrolyte to produce the flexible, solid-state supercapacitors.

“Nunzio’s team is making important advances in the energy-storage area, and we were glad to see that our carbon nanotube film technology was able to provide breakthrough current collection capability to further improve their devices,” said Pasquali, a Rice professor of chemical and biomolecular engineering and chemistry. “This nice collaboration is definitely bottom-up, as one of Nunzio’s Ph.D. students, Marco Notarianni, spent a year in our lab during his Master of Science research period a few years ago.”

“We built on our earlier work on CNT films published in ACS Nano, where we developed a solution-based technique to produce carbon nanotube films for transparent electrodes in displays,” said Francesca Mirri, a graduate student in Pasquali’s research group and co-author of the papers. “Now we see that carbon nanotube films produced by the solution-processing method can be applied in several areas.”

As currently designed, the supercapacitors can be charged through regenerative braking and are intended to work alongside the lithium-ion batteries in electric vehicles, said co-author Notarianni, a Queensland graduate student.

“Vehicles need an extra energy spurt for acceleration, and this is where supercapacitors come in. They hold a limited amount of charge, but with their high power density, deliver it very quickly, making them the perfect complement to mass-storage batteries,” he said.

Because hundreds of film supercapacitors are used in the panel, the electric energy required to power the car’s battery can be stored in the car body. “Supercapacitors offer a high power output in a short time, meaning a faster acceleration rate of the car and a charging time of just a few minutes, compared with several hours for a standard electric car battery,” Notarianni said.

The researchers foresee such panels will eventually replace standard lithium-ion batteries. “In the future, it is hoped the supercapacitor will be developed to store more energy than an ionic battery while retaining the ability to release its energy up to 10 times faster – meaning the car would be powered by the supercapacitors in its body panels,” said Queensland postdoctoral researcher Jinzhang Liu.

Here’s an image of graphene infused with carbon nantoubes used in the supercapacitor film,

A scanning electron microscope image shows freestanding graphene film with carbon nanotubes attached. The material is part of a project to create lightweight films containing super capacitors that charge quickly and store energy. Courtesy of Nunzio Motta/Queensland University of Technology - See more at: http://news.rice.edu/2014/11/07/supercharged-panels-may-power-cars/#sthash.0RPsIbMY.dpuf

A scanning electron microscope image shows freestanding graphene film with carbon nanotubes attached. The material is part of a project to create lightweight films containing super capacitors that charge quickly and store energy. Courtesy of Nunzio Motta/Queensland University of Technology

Here are links to and citations for the two papers published by the researchers,

Graphene-based supercapacitor with carbon nanotube film as highly efficient current collector by Marco Notarianni, Jinzhang Liu, Francesca Mirri, Matteo Pasquali, and Nunzio Motta. Nanotechnology Volume 25 Number 43 doi:10.1088/0957-4484/25/43/435405

High performance all-carbon thin film supercapacitors by Jinzhang Liu, Francesca Mirri, Marco Notarianni, Matteo Pasquali, and Nunzio Motta. Journal of Power Sources Volume 274, 15 January 2015, Pages 823–830 DOI: 10.1016/j.jpowsour.2014.10.104

Both articles are behind paywalls.

One final note, Dexter Johnson provides some insight into issues with graphene-based supercapacitors and what makes this proposed application attractive in his Nov. 7, 2014 post on the Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website; Note: Links have been removed),

The hope has been that someone could make graphene electrodes for supercapacitors that would boost their energy density into the range of chemical-based batteries. The supercapacitors currently on the market have on average an energy density around 28 Wh/kg, whereas a Li-ion battery holds about 200Wh/kg. That’s a big gap to fill.

The research in the field thus far has indicated that graphene’s achievable surface area in real devices—the factor that determines how many ions a supercapacitor electrode can store, and therefore its energy density—is not any better than traditional activated carbon. In fact, it may not be much better than a used cigarette butt.

Though graphene may not help increase supercapacitors’ energy density, its usefulness in this application may lie in the fact that its natural high conductivity will allow superconductors to operate at higher frequencies than those that are currently on the market. Another likely benefit that graphene will yield comes from the fact that it can be structured and scaled down, unlike other supercapacitor materials.

I recommend reading Dexter’s commentary in its entirety.

*’University of Queensland’ corrected to “Queensland University of Technology’ on Nov. 10, 2014 at 1335 PST.

Researching a curcumin delivery system—a nutraceutical story

A Nov. 6, 2014 news item on ScienceDaily features research on delivering curcumin’s (a constituent of turmeric) health benefits more efficiently (there is a twist; for the impatient, you may want to scroll down to where I provide an excerpt from the university’s news release) from Ohio State University (US),

The health benefits of over-the-counter curcumin supplements might not get past your gut, but new research shows that a modified formulation of the spice releases its anti-inflammatory goodness throughout the body.

Curcumin is a naturally occurring compound found in the spice turmeric that has been used for centuries as an Ayurvedic medicine treatment for such ailments as allergies, diabetes and ulcers.

Anecdotal and scientific evidence suggests curcumin promotes health because it lowers inflammation, but it is not absorbed well by the body. Most curcumin in food or supplements stays in the gastrointestinal tract, and any portion that’s absorbed is metabolized quickly.

A Nov. 6, 2014 Ohio State University news release by Emily Caldwell (also on EurekAlert), which originated the news item, explains the interest in curcumin in more detail and describes the research in more detail,

Many research groups are testing the compound’s effects on disorders ranging from colon cancer to osteoarthritis. Others, like these Ohio State University scientists, are investigating whether enabling widespread availability of curcumin’s biological effects to the entire body could make it useful both therapeutically and as a daily supplement to combat disease.

“There’s a reason why this compound has been used for hundreds of years in Eastern medicine. And this study suggests that we have identified a better and more effective way to deliver curcumin and know what diseases to use it for so that we can take advantage of its anti-inflammatory power,” said Nicholas Young, a postdoctoral researcher in rheumatology and immunology at Ohio State and lead author of the study.

Curcumin powder was mixed with castor oil and polyethylene glycol in a process called nano-emulsion (think vinaigrette salad dressing), creating fluid teeming with microvesicles that contain curcumin. This process allows the compound to dissolve and be more easily absorbed by the gut to enter the bloodstream and tissues.

Feeding mice this curcumin-based drug shut down an acute inflammatory reaction by blocking activation of a key protein that triggers the immune response. The researchers were also the first to show that curcumin stops recruitment of specific immune cells that, when overactive, are linked to such problems as heart disease and obesity.

Young and his colleagues, including co-senior authors Lai-Chu Wu and Wael Jarjour of the Division of Rheumatology and Immunology at Ohio State’s Wexner Medical Center, now want to know if curcumin in this form can counter the chronic inflammation that is linked to sickness and age-related frailty. They have started with animal studies testing nano-emulsified curcumin’s ability to prevent or control inflammation in a lupus model.

“We envision that this nutraceutical could be used one day both as a daily supplement to help prevent certain diseases and as a therapeutic drug to help combat the bad inflammation observed in many diseases,” Young said. “The distinction will then be in the amount given – perhaps a low dose for daily prevention and higher doses for disease suppression.”

The term nutraceutical refers to foods or nutrients that provide medical or health benefits.

This news release notes the latest research is built on previous work,

The curcumin delivery system was created in Ohio State’s College of Pharmacy, and these researchers previously showed that concentrations of the emulsified curcumin in blood were more than 10 times higher than of curcumin powder suspended in water.

A more precise description of the current research is then provided (from the news release),

… From there, the researchers launched experiments in mice and cell cultures, generating artificial inflammation and comparing the effects of the nano-emulsified curcumin with the effects of curcumin powder in water or no treatment at all. [emphasis mine]

The researchers injected mice with lipopolysaccharide, a bacteria cell wall extract that stimulates an immune reaction in animals. Curcumin can target many molecules, but the research team zeroed in on NF-kB, a protein that is known to play an important role in the immune response.

In a specialized imaging machine, mice receiving plain curcumin lit up with bioluminescent signals indicating that NF-kB was actively triggering an immune response, while mice receiving nano-emulsified curcumin showed minimal signs – a 22-fold reduction – that the protein had been activated at all.

Knowing that curcumin delivered in this way could shut down NF-kB activation throughout the animals’ bodies, researchers looked for further details about the compound’s effects on inflammation. They found that nano-emulsified curcumin halted the recruitment of immune cells called macrophages that “eat” invading pathogens but also contribute to inflammation by secreting pro-inflammatory chemicals. And in cells isolated from human blood samples, macrophages were stopped in their tracks.

“This macrophage-specific effect of curcumin had not been described before,” Young said. “Because of that finding, we propose nano-emulsified curcumin has the best potential against macrophage-associated inflammation.”

Inflammation triggered by overactive macrophages has been linked to cardiovascular disease, disorders that accompany obesity, Crohn’s disease, rheumatoid arthritis, inflammatory bowel disease, diabetes and lupus-related nephritis.

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

Oral Administration of Nano-Emulsion Curcumin in Mice Suppresses Inflammatory-Induced NFκB Signaling and Macrophage Migration by Nicholas A. Young, Michael S. Bruss, Mark Gardner, William L. Willis, Xiaokui Mo, Giancarlo R. Valiente, Yu Cao, Zhongfa Liu, Wael N. Jarjour, and Lai-Chu Wu. PLOS ONE Published: November 04, 2014 DOI: 10.1371/journal.pone.0111559

This paper is open accesss.

I have an Oct. 1, 2014 posting which features research on curcumin for healing wounds and on tumerone for stimulating the formation of stem cells in the brain.

Bomb-sniffing and other sniffing possibilities from Utah (US state)

A Nov. 4, 2014 news item on Phys.org features some research in Utah on the use of carbon nanotubes for sensing devices,

University of Utah engineers have developed a new type of carbon nanotube material for handheld sensors that will be quicker and better at sniffing out explosives, deadly gases and illegal drugs.

A carbon nanotube is a cylindrical material that is a hexagonal or six-sided array of carbon atoms rolled up into a tube. Carbon nanotubes are known for their strength and high electrical conductivity and are used in products from baseball bats and other sports equipment to lithium-ion batteries and touchscreen computer displays.

Vaporsens, a university spin-off company, plans to build a prototype handheld sensor by year’s end and produce the first commercial scanners early next year, says co-founder Ling Zang, a professor of materials science and engineering and senior author of a study of the technology published online Nov. 4 [2014] in the journal Advanced Materials.

The new kind of nanotubes also could lead to flexible solar panels that can be rolled up and stored or even “painted” on clothing such as a jacket, he adds.

Here’s Ling Zang holding a prototype of the device,

Ling Zang, a University of Utah professor of materials science and engineering, holds a prototype detector that uses a new type of carbon nanotube material for use in handheld scanners to detect explosives, toxic chemicals and illegal drugs. Zang and colleagues developed the new material, which will make such scanners quicker and more sensitive than today’s standard detection devices. Ling’s spinoff company, Vaporsens, plans to produce commercial versions of the new kind of scanner early next year. Courtesy: University of Utah

Ling Zang, a University of Utah professor of materials science and engineering, holds a prototype detector that uses a new type of carbon nanotube material for use in handheld scanners to detect explosives, toxic chemicals and illegal drugs. Zang and colleagues developed the new material, which will make such scanners quicker and more sensitive than today’s standard detection devices. Ling’s spinoff company, Vaporsens, plans to produce commercial versions of the new kind of scanner early next year. Courtesy: University of Utah

A Nov. 4, 2014 University of Utah news release (also on EurekAlert), which originated the news item, provides more detail about the research,

Zang and his team found a way to break up bundles of the carbon nanotubes with a polymer and then deposit a microscopic amount on electrodes in a prototype handheld scanner that can detect toxic gases such as sarin or chlorine, or explosives such as TNT.

When the sensor detects molecules from an explosive, deadly gas or drugs such as methamphetamine, they alter the electrical current through the nanotube materials, signaling the presence of any of those substances, Zang says.

“You can apply voltage between the electrodes and monitor the current through the nanotube,” says Zang, a professor with USTAR, the Utah Science Technology and Research economic development initiative. “If you have explosives or toxic chemicals caught by the nanotube, you will see an increase or decrease in the current.”

By modifying the surface of the nanotubes with a polymer, the material can be tuned to detect any of more than a dozen explosives, including homemade bombs, and about two-dozen different toxic gases, says Zang. The technology also can be applied to existing detectors or airport scanners used to sense explosives or chemical threats.

Zang says scanners with the new technology “could be used by the military, police, first responders and private industry focused on public safety.”

Unlike the today’s detectors, which analyze the spectra of ionized molecules of explosives and chemicals, the Utah carbon-nanotube technology has four advantages:

• It is more sensitive because all the carbon atoms in the nanotube are exposed to air, “so every part is susceptible to whatever it is detecting,” says study co-author Ben Bunes, a doctoral student in materials science and engineering.

• It is more accurate and generates fewer false positives, according to lab tests.

• It has a faster response time. While current detectors might find an explosive or gas in minutes, this type of device could do it in seconds, the tests showed.

• It is cost-effective because the total amount of the material used is microscopic.

This study was funded by the Department of Homeland Security, Department of Defense, National Science Foundation and NASA. …

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

Photodoping and Enhanced Visible Light Absorption in Single-Walled Carbon Nanotubes Functionalized with a Wide Band Gap Oligomer by Benjamin R. Bunes, Miao Xu, Yaqiong Zhang, Dustin E. Gross, Avishek Saha, Daniel L. Jacobs, Xiaomei Yang, Jeffrey S. Moore, and Ling Zang. Advanced Materials DOI: 10.1002/adma.201404112 Article first published online: 4 NOV 2014

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

For anyone curious about Vaporsens, you can find more here.

Solar cells and ‘tinkertoys’

A Nov. 3, 2014 news item on Nanowerk features a project researchers hope will improve photovoltaic efficiency and make solar cells competitive with other sources of energy,

 Researchers at Sandia National Laboratories have received a $1.2 million award from the U.S. Department of Energy’s SunShot Initiative to develop a technique that they believe will significantly improve the efficiencies of photovoltaic materials and help make solar electricity cost-competitive with other sources of energy.

The work builds on Sandia’s recent successes with metal-organic framework (MOF) materials by combining them with dye-sensitized solar cells (DSSC).

“A lot of people are working with DSSCs, but we think our expertise with MOFs gives us a tool that others don’t have,” said Sandia’s Erik Spoerke, a materials scientist with a long history of solar cell exploration at the labs.

A Nov. 3, 2014 Sandia National Laboratories news release, which originated the news item, describes the project and the technology in more detail,

Sandia’s project is funded through SunShot’s Next Generation Photovoltaic Technologies III program, which sponsors projects that apply promising basic materials science that has been proven at the materials properties level to demonstrate photovoltaic conversion improvements to address or exceed SunShot goals.

The SunShot Initiative is a collaborative national effort that aggressively drives innovation with the aim of making solar energy fully cost-competitive with traditional energy sources before the end of the decade. Through SunShot, the Energy Department supports efforts by private companies, universities and national laboratories to drive down the cost of solar electricity to 6 cents per kilowatt-hour.

DSSCs provide basis for future advancements in solar electricity production

Dye-sensitized solar cells, invented in the 1980s, use dyes designed to efficiently absorb light in the solar spectrum. The dye is mated with a semiconductor, typically titanium dioxide, that facilitates conversion of the energy in the optically excited dye into usable electrical current.

DSSCs are considered a significant advancement in photovoltaic technology since they separate the various processes of generating current from a solar cell. Michael Grätzel, a professor at the École Polytechnique Fédérale de Lausanne in Switzerland, was awarded the 2010 Millennium Technology Prize for inventing the first high-efficiency DSSC.

“If you don’t have everything in the DSSC dependent on everything else, it’s a lot easier to optimize your photovoltaic device in the most flexible and effective way,” explained Sandia senior scientist Mark Allendorf. DSSCs, for example, can capture more of the sun’s energy than silicon-based solar cells by using varied or multiple dyes and also can use different molecular systems, Allendorf said.

“It becomes almost modular in terms of the cell’s components, all of which contribute to making electricity out of sunlight more efficiently,” said Spoerke.

MOFs’ structure, versatility and porosity help overcome DSSC limitations

Though a source of optimism for the solar research community, DSSCs possess certain challenges that the Sandia research team thinks can be overcome by combining them with MOFs.

Allendorf said researchers hope to use the ordered structure and versatile chemistry of MOFs to help the dyes in DSSCs absorb more solar light, which he says is a fundamental limit on their efficiency.

“Our hypothesis is that we can put a thin layer of MOF on top of the titanium dioxide, thus enabling us to order the dye in exactly the way we want it,” Allendorf explained. That, he said, should avoid the efficiency-decreasing problem of dye aggregation, since the dye would then be locked into the MOF’s crystalline structure.

MOFs are highly-ordered materials that also offer high levels of porosity, said Allendorf, a MOF expert and 29-year veteran of Sandia. He calls the materials “Tinkertoys for chemists” because of the ease with which new structures can be envisioned and assembled. [emphasis mine]

Allendorf said the unique porosity of MOFs will allow researchers to add a second dye, placed into the pores of the MOF, that will cover additional parts of the solar spectrum that weren’t covered with the initial dye. Finally, he and Spoerke are convinced that MOFs can help improve the overall electron charge and flow of the solar cell, which currently faces instability issues.

“Essentially, we believe MOFs can help to more effectively organize the electronic and nano-structure of the molecules in the solar cell,” said Spoerke. “This can go a long way toward improving the efficiency and stability of these assembled devices.”

In addition to the Sandia team, the project includes researchers at the University of Colorado-Boulder, particularly Steve George, an expert in a thin film technology known as atomic layer deposition.

The technique, said Spoerke, is important in that it offers a pathway for highly controlled materials chemistry with potentially low-cost manufacturing of the DSSC/MOF process.

“With the combination of MOFs, dye-sensitized solar cells and atomic layer deposition, we think we can figure out how to control all of the key cell interfaces and material elements in a way that’s never been done before,” said Spoerke. “That’s what makes this project exciting.”

Here’s a picture showing an early Tinkertoy set,

Original Tinkertoy, Giant Engineer #155. Questor Education Products Co., c.1950 [downloaded from http://en.wikipedia.org/wiki/Tinkertoy#mediaviewer/File:Tinkertoy_300126232168.JPG]

Original Tinkertoy, Giant Engineer #155. Questor Education Products Co., c.1950 [downloaded from http://en.wikipedia.org/wiki/Tinkertoy#mediaviewer/File:Tinkertoy_300126232168.JPG]

The Tinkertoy entry on Wikipedia has this,

The Tinkertoy Construction Set is a toy construction set for children. It was created in 1914—six years after the Frank Hornby’s Meccano sets—by Charles H. Pajeau and Robert Pettit and Gordon Tinker in Evanston, Illinois. Pajeau, a stonemason, designed the toy after seeing children play with sticks and empty spools of thread. He and Pettit set out to market a toy that would allow and inspire children to use their imaginations. At first, this did not go well, but after a year or two over a million were sold.

Shrinky Dinks, tinkertoys, Lego have all been mentioned here in conjunction with lab work. I’m always delighted to see scientists working with or using children’s toys as inspiration of one type or another.

Nanosafety research: a quality control issue

Toxicologist Dr. Harald Krug has published a review of several thousand studies on nanomaterials safety exposing problematic research methodologies and conclusions. From an Oct. 29, 2014 news item on Nanowerk (Note: A link has been removed),

Empa [Swiss Federal Laboratories for Materials Science and Technology] toxicologist Harald Krug has lambasted his colleagues in the journal Angewandte Chemie (“Nanosafety Research—Are We on the Right Track?”). He evaluated several thousand studies on the risks associated with nanoparticles and discovered no end of shortcomings: poorly prepared experiments and results that don’t carry any clout. Instead of merely leveling criticism, however, Empa is also developing new standards for such experiments within an international network.

An Oct. 29, 2014 Empa press release (also on EurekAlert), which originated the news item, describes the new enthusiasm for research into nanomaterials and safety,

Researching the safety of nanoparticles is all the rage. Thousands of scientists worldwide are conducting research on the topic, examining the question of whether titanium dioxide nanoparticles from sun creams can get through the skin and into the body, whether carbon nanotubes from electronic products are as hazardous for the lungs as asbestos used to be or whether nanoparticles in food can get into the blood via the intestinal flora, for instance. Public interest is great, research funds are flowing – and the number of scientific projects is skyrocketing: between 1980 and 2010, a total of 5,000 projects were published, followed by another 5,000 in just the last three years. However, the amount of new knowledge has only increased marginally. After all, according to Krug the majority of the projects are poorly executed and all but useless for risk assessments.

The press release goes on to describe various pathways into the body and problems with research methodologies,

How do nanoparticles get into the body?

Artificial nanoparticles measuring between one and 100 nanometers in size can theoretically enter the body in three ways: through the skin, via the lungs and via the digestive tract. Almost every study concludes that healthy, undamaged skin is an effective protective barrier against nanoparticles. When it comes to the route through the stomach and gut, however, the research community is at odds. But upon closer inspection the value of many alarmist reports is dubious – such as when nanoparticles made of soluble substances like zinc oxide or silver are being studied. Although the particles disintegrate and the ions drifting into the body are cytotoxic, this effect has nothing to do with the topic of nanoparticles but is merely linked to the toxicity of the (dissolved) substance and the ingested dose.

Laboratory animals die in vain – drastic overdoses and other errors

Krug also discovered that some researchers maltreat their laboratory animals with absurdly high amounts of nanoparticles. Chinese scientists, for instance, fed mice five grams of titanium oxide per kilogram of body weight, without detecting any effects. By way of comparison: half the amount of kitchen salt would already have killed the animals. A sloppy job is also being made of things in the study of lung exposure to nanoparticles: inhalation experiments are expensive and complex because a defined number of particles has to be swirled around in the air. Although it is easier to place the particles directly in the animal’s windpipe (“instillation”), some researchers overdo it to such an extent that the animals suffocate on the sheer mass of nanoparticles.

While others might well make do without animal testing and conduct in vitro experiments on cells, here, too, cell cultures are covered by layers of nanoparticles that are 500 nanometers thick, causing them to die from a lack of nutrients and oxygen alone – not from a real nano-effect. And even the most meticulous experiment is worthless if the particles used have not been characterized rigorously beforehand. Some researchers simply skip this preparatory work and use the particles “straight out of the box”. Such experiments are irreproducible, warns Krug.

As noted in the news item, the scientists at Empa have devised a solution to some to of the problems (from the press release),

The solution: inter-laboratory tests with standard materials
Empa is thus collaborating with research groups like EPFL’s Powder Technology Laboratory, with industrial partners and with Switzerland’s Federal Office of Public Health (FOPH) to find a solution to the problem: on 9 October the “NanoScreen” programme, one of the “CCMX Materials Challenges”, got underway, which is expected to yield a set of pre-validated methods for lab experiments over the next few years. It involves using test materials that have a closely defined particle size distribution, possess well-documented biological and chemical properties and can be altered in certain parameters – such as surface charge. “Thanks to these methods and test substances, international labs will be able to compare, verify and, if need be, improve their experiments,” explains Peter Wick, Head of Empa’s laboratory for Materials-Biology Interactions.

Instead of the all-too-familiar “fumbling around in the dark”, this would provide an opportunity for internationally coordinated research strategies to not only clarify the potential risks of new nanoparticles in retrospect but even be able to predict them. The Swiss scientists therefore coordinate their research activities with the National Institute of Standards and Technology (NIST) in the US, the European Commission’s Joint Research Center (JRC) and the Korean Institute of Standards and Science (KRISS).

Bravo! and thank you Dr. Krug and Empa for confirming something I’ve suspected due to hints from more informed commentators. Unfortunately my ignorance. about research protocols has not permitted me to undertake a better analysis of the research. ,

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

Nanosafety Research—Are We on the Right Track? by Prof. Dr. Harald F. Krug. Angewandte Chemie International Edition DOI: 10.1002/anie.201403367 Article first published online: 10 OCT 2014

This is an open access paper.

Bipolar disorder at the nanoscale

In all the talk generated by the various brain projects (BRAIN initiative [US], The Human Brain Project [European Union], Brain Canada), there’s remarkably little discussion about mental illness. So, this news is a little unusual.

Using super-high resolution technique scientists at Northwestern University (Chicago, Illinois, US) believe they’ve made a discovery which explains how bipolar disorder affects the brain according to an Oct. 22, 2014 Northwestern University news release (also on EurekAlert and ScienceDaily) by Erin White,

Scientists used a new super-resolution imaging method — the same method recognized with the 2014 Nobel Prize in chemistry — to peer deep into brain tissue from mice with bipolar-like behaviors. In the synapses (where communication between brain cells occurs), they discovered tiny “nanodomain” structures with concentrated levels of ANK3 — the gene most strongly associated with bipolar disorder risk. ANK3 is coding for the protein ankyrin-G.

“We knew that ankyrin-G played an important role in bipolar disease, but we didn’t know how,” said Northwestern Medicine scientist Peter Penzes, corresponding author of the paper. “Through this imaging method we found the gene formed in nanodomain structures in the synapses, and we determined that these structures control or regulate the behavior of synapses.”

Penzes is a professor in physiology and psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. The results were published Oct. 22 in the journal Neuron.

High-profile cases, including actress Catherine Zeta-Jones and politician Jesse Jackson, Jr., have brought attention to bipolar disorder. The illness causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. About 3 percent of Americans experience bipolar disorder symptoms, and there is no cure.

Recent large-scale human genetic studies have shown that genes can contribute to disease risk along with stress and other environmental factors. However, how these risk genes affect the brain is not known.

This is the first time any psychiatric risk gene has been analyzed at such a detailed level of resolution. As explained in the paper, Penzes used the Nikon Structured Illumination Super-resolution Microscope to study a mouse model of bipolar disorder. The microscope realizes resolution of up to 115 nanometers. To put that size in perspective, a nanometer is one-tenth of a micron, and there are 25,400 microns in one inch. Very few of these microscopes exist worldwide.

“There is important information about genes and diseases that can only been seen at this level of resolution,” Penzes said. “We provide a neurobiological explanation of the function of the leading risk gene, and this might provide insight into the abnormalities in bipolar disorder.”

The biological framework presented in this paper could be used in human studies of bipolar disorder in the future, with the goal of developing therapeutic approaches to target these genes.

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

Psychiatric Risk Factor ANK3/Ankyrin-G Nanodomains Regulate the Structure and Function of Glutamatergic Synapses by Katharine R. Smith, Katherine J. Kopeikina, Jessica M. Fawcett-Patel, Katherine Leaderbrand, Ruoqi Gao, Britta Schürmann, Kristoffer Myczek, Jelena Radulovic, Geoffrey T. Swanson, and Peter Penzes. Neuron, Volume 84, Issue 2, p399–415, 22 October 2014 DOI: http://dx.doi.org/10.1016/j.neuron.2014.10.010

This paper is behind a paywall.

You can find more about super-high resolution and nanoscopy in my Oct. 8, 2014 post about the 2014 Nobel Chemistry prize winners.