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CRISPR gene editing technique and patents

I have two items about the CRISPR gene editing technique. The first concerns a new use for the CRISPR technique developed by researchers at Johns Hopkins University School of Medicine described in a Jan. 5, 2015 Johns Hopkins University news release on EurekAlert,

A powerful “genome editing” technology known as CRISPR has been used by researchers since 2012 to trim, disrupt, replace or add to sequences of an organism’s DNA. Now, scientists at Johns Hopkins Medicine have shown that the system also precisely and efficiently alters human stem cells.

“Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs [human-induced pluripotent stem cells] for human therapy aren’t that far away,” says Zhaohui Ye, Ph.D., an instructor of medicine at the Johns Hopkins University School of Medicine. “This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells.”

CRISPR originated from a microbial immune system that contains DNA segments known as clustered regularly interspaced short palindromic repeats. The engineered editing system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions far more efficiently than other gene editing techniques, such as TALEN, short for transcription activator-like effector nuclease.

Despite CRISPR’s advantages, a recent study suggested that it might also produce a large number of “off-target” effects in human cancer cell lines, specifically modification of genes that researchers didn’t mean to change.

To see if this unwanted effect occurred in other human cell types, Ye; Linzhao Cheng, Ph.D., a professor of medicine and oncology in the Johns Hopkins University School of Medicine; and their colleagues pitted CRISPR against TALEN in human iPSCs, adult cells reprogrammed to act like embryonic stem cells. Human iPSCs have already shown enormous promise for treating and studying disease.

The researchers compared the ability of both genome editing systems to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another. As model genes, the researchers used JAK2, a gene that when mutated causes a bone marrow disorder known as polycythemia vera; SERPINA1, a gene that when mutated causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that’s been recently discovered to be a “safe harbor” in the human genome for inserting foreign genes.

Their comparison found that when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all three gene systems, inducing up to 100 times more cuts. However, when using these genome editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs, the researchers report.

Contrary to results of the human cancer cell line study, both CRISPR and TALEN had the same targeting specificity in human iPSCs, hitting only the genes they were designed to affect, the team says. The researchers also found that the CRISPR system has an advantage over TALEN: It can be designed to target only the mutation-containing gene without affecting the healthy gene in patients, where only one copy of a gene is affected.

The findings, together with a related study that was published earlier in a leading journal of stem cell research (Cell Stem Cell), offer reassurance that CRISPR will be a useful tool for editing the genes of human iPSCs with little risk of off-target effects, say Ye and Cheng.

“CRISPR-mediated genome editing opens the door to many genetic applications in biologically relevant cells that can lead to better understanding of and potential cures for human diseases,” says Cheng.

Here’s a link to and citation for the paper by the Johns Hopkins researchers,

Efficient and Allele-Specific Genome Editing of Disease Loci in Human iPSCs by Cory Smith, Leire Abalde-Atristain, Chaoxia He, Brett R Brodsky, Evan M Braunstein, Pooja Chaudhari, Yoon-Young Jang, Linzhao Cheng and Zhaohui Ye. Molecular Therapy (24 November 2014) | doi:10.1038/mt.2014.226

This paper is behind a paywall.

Not mentioned in the Johns Hopkins Medicine news release is a brewing patent battle over the CRISPR technique. A Dec. 31, 2014 post by Glyn Moody for Techdirt lays out the situation (Note: Links have been removed),

Although not many outside the world of the biological sciences have heard of it yet, the CRISPR gene editing technique may turn out to be one of the most important discoveries of recent years — if patent battles don’t ruin it. Technology Review describes it as:

    an invention that may be the most important new genetic engineering technique since the beginning of the biotechnology age in the 1970s. The CRISPR system, dubbed a “search and replace function” for DNA, lets scientists easily disable genes or change their function by replacing DNA letters. During the last few months, scientists have shown that it’s possible to use CRISPR to rid mice of muscular dystrophy, cure them of a rare liver disease, make human cells immune to HIV, and genetically modify monkeys.

Unfortunately, rivalry between scientists claiming the credit for key parts of CRISPR threatens to spill over into patent litigation …

Moody describes three scientists vying for control via their patents,

[A researcher at the MIT-Harvard Broad Institute, Feng] Zhang cofounded Editas Medicine, and this week the startup announced that it had licensed his patent from the Broad Institute. But Editas doesn’t have CRISPR sewn up.

That’s because [Jennifer] Doudna, a structural biologist at the University of California, Berkeley, was a cofounder of Editas, too. And since Zhang’s patent came out, she’s broken off with the company, and her intellectual property — in the form of her own pending patent — has been licensed to Intellia, a competing startup unveiled only last month.

Making matters still more complicated, [another CRISPR researcher, Emmanuelle] Charpentier sold her own rights in the same patent application to CRISPR Therapeutics.

Moody notes,

Whether obvious or not, it looks like the patent granted may complicate turning the undoubtedly important CRISPR technique into products. That, in its turn, will mean delays for life-changing and even life-saving therapies: for example, CRISPR could potentially allow the defective gene that causes serious problems for those with cystic fibrosis to be edited to produce normal proteins, thus eliminating those problems.

It’s dispiriting to think that potentially valuable therapies could be lost to litigation battles particularly since the researchers are academics and their work was funded by taxpayers. In any event, I hope sanity reigns and they are able to avoid actions which will grind research down to a standstill.

Belated Merry Christmas and Season’s Greetings

Thanks to Jennifer Crusie’s Dec. 25, 2014 post on her Argh Ink blog I found this delightful Chrismas card/ song,


Here’s more about the cartoonist and the singers,

Uploaded on Nov 7, 2007

Sung by The Drifters. Cartoon by Joshua Held.
Featuring Bill Pinkney on lead bass and Clyde McPhatter on tenor.
An animated Christmas Card, and a homage to a great song, a great band, and a great Holiday.

This cartoon’s official Facebook page: https://www.facebook.com/pages/White-…

More me on: http://www.joshuaheld.com

From the bottom of my heart, thank you all for reading this blog today and any and every other day you’ve cared to do so. II wish you the best of the season and for the coming year.

2014 Maddox Prize winners and more ( a letter writing compaign)* from Sense about Science*

The UK’s ‘Sense about Science’ organization announced the two winners of its 2014 John Maddox (aka, the ‘standing up for science’) Prize in late October 2014 (from the Oct. 28, 2014 announcement),

I am delighted to share that last night [Oct. 27, 2014] Dr Emily Willingham and Dr David Robert Grimes were announced as the winners of the 2014 John Maddox Prize, at our annual reception held with the Royal Pharmaceutical Society.

After lengthy deliberation, this year’s judges (Tracey Brown, Philip Campbell, Colin Blakemore and Martin Rees) awarded the prize to these two people who embody the spirit of the prize, showing courage in promoting science and evidence on a matter of public interest, despite facing difficulty and hostility in doing so.

The call for 2014 nominations was mentioned in an Aug. 18, 2014 post. Here’s more about each of the winners (from the 2014 John Maddox Prize webpage on the Sense about Science website),

The judges awarded the prize to freelance journalist Dr Emily Willingham and early career scientist Dr David Robert Grimes for courage in promoting science and evidence on a matter of public interest, despite facing difficulty and hostility in doing so. …

David Grimes writes bravely on challenging and controversial issues, including nuclear power and climate change. He has persevered despite hostility and threats, such as on his writing about the evidence in the debate on abortion in Ireland. He does so while sustaining his career as a scientist at the University of Oxford.

Emily Willingham, a US writer, has brought discussion about evidence, from school shootings to home birth, to large audiences through her writing. She has continued to reach across conflict and disputes about evidence to the people trying to make sense of them. She is facing a lawsuit for an article about the purported link between vaccines and autism.

A Nov. 1, 2014 post by Nick Cohen for the Guardian newspaper discusses one of the 2014 winners in the context of a post about standing up to science ignorance and Ebola in the US, scroll down abut 15% of the way),

The joint winners confronted beliefs that are as prevalent in Britain as America: that vaccination causes autism, that homeopathic medicines work, that manmade climate change does not exist and that adding fluoride to the water supply is a threat to health. (I didn’t know it until the prize jury told me but Sinn Féin is leading a vigorous anti-fluoride campaign in Dublin – well, I suppose it’s progress for the IRA to go from blowing off peoples’ heads to merely rotting their teeth.)

David Robert Grimes, one of the winners, said that, contrary to the myth of the scientific bully, most of his colleagues wanted to keep out of public debate, presumably because they did not wish to receive the threats of violence fanatics and quacks have directed at him. If we are to improve public policy in areas as diverse as the fight against Ebola to the treatment of drug addicts, they need to be a braver, and more willing to tell the public, which so often funds their research, what they have learned.

Grimes makes a useful distinction. Most people just want more information and scientists should be prepared to make their case clearly and concisely. Then there are the rest – Ukip, the Tea Party, governors of Maine, Sinn Féin, David Cameron, climate change deniers – who will block out any evidence that contradicts their beliefs. They confirm the truth of Paul Simon’s line: “All lies and jest, still the man hears what he wants to hear and disregards the rest.”

Lydia Lepage (a post-doctoral researcher at the University of Edinburgh and a member of the Voice of Young Science, which is run by Sense About Science) over on the Conversation writes about both winners in an Oct. 28, 2014 post (Note: Links have been removed),

Willingham is a freelance science journalist whose evidence-based article: “Blame Wakefield for missed autism-gut connection” drew intense criticism and a lawsuit from Andrew Wakefield, the discredited scientist known for his now-retracted 1998 Lancet paper on the alleged link between vaccines and autism. She criticised the “red herring and the subsequent noxious cloud that his fraud left over any research examining autism and the gut”.

Willingham’s self-declared passion is “presenting accurate, evidence-based information”. She says:

Standing up for science and public health in the face of not only unyielding but also sometimes threatening opposition can be tiring and demoralising.

Grimes is a post-doctoral researcher at the University of Oxford in the UK, working on modelling oxygen distribution in tumours. He has been awarded the Maddox Prize for reaching out to the public through his writing on a range of challenging and controversial issues, including nuclear power and climate change.

Grimes continues to present the evidence, despite receiving threats, particularly surrounding discussion on abortion in Ireland. Following his article on six myths about cancer, in which he addressed the “dubious and outlandish” information that can be found on the internet, he received physical and digital hate-mail.

Sense about Science next announced an ‘Ask for Evidence’ website, from a Nov. 2, 2014 announcement,

We are excited to announce that Ask for Evidence online is now live! And people are already using it to ask for the evidence behind claims they’ve come across. Check out www.askforevidence.org

It’s our new interactive website that makes asking for evidence and getting help understanding that evidence as easy as possible. You can use it to ask politicians, companies, NGOs and anyone else for evidence behind their claims, while you’re on the train, walking down the street or sitting in front of the TV. And if you need help understanding the evidence you’ve been sent, that’s there too. With the help of partners and friends we’ve built a help centre that has captured what we’ve learnt over the past 12 years answering thousands of requests for help in understanding evidence.

Finally,. there’s the latest announcement about an effort to influence the World Health Organization’s (WHO) new policy on reporting the results of clinical trials, from the Nov. 11, 2014 announcement,

Following our pressure, the World Health Organization is drafting a policy on reporting the results of clinical trials.

We have to grab this fantastic opportunity with both hands and make sure that the most influential health body in the world comes out with a statement that strongly supports clinical trials transparency.

But you only have until Saturday 15th November 2014 to add your voice.

The draft WHO policy does not call for the disclosure of the results of past trials, only future ones. The vast majority of medicines we use every day were approved by regulators a decade or more ago and so were tested in clinical trials over the past decades.

So email the WHO to tell them their policy should:

  1. Call for the results of all past clinical trials to be reported, as well as all future clinical trials.
  2. Require results to be reported within 12 months, rather than permitting delays of 18-30 months. The USA’s FDA Amendment Act, the newly adopted EU Clinical Trials Regulation and pharmaceutical companies including GSK and LEO Pharma all agree that 12 months is enough time to report results.
  3. Encourage researchers to put results on publicly accessible registers, in useful, standardised formats.

Email [email protected] today.

Be sure to include your name and contact details as the WHO will not consider anonymous comments.

You can also use the full AllTrials response to write your email if you wish.

Read the full AllTrials response.

I am encouraged to see a move towards more transparency in reporting the results of clinical trials whether or not this bid to include past clinical trials is successful, although that would certainly be excellent news.

* (a letter writing campaign) was added to the head and ‘sense about science’ was changed to ‘Sense about Science’ on Nov. 14, 2014 1015 hundred hours PDT.

Simon Fraser University – SCFC861Nanotechnology, The Next Big Idea: course Week 2

Yesterday (Oct. 30, 2014) I taught week 2 of a course called, Nanotechnology: The Next Big Idea for Simon Fraser University’s (SFU) Continuing Studies programme. At the end of this post you will find a link to my Week Two PowerPoint slides and notes of a sort.

For those who may be mildly curious, here’s a description of what was covered in the second week (from SFU’s course description webpage),

Week 2: Not as New as You Might Think

The thinking that underlies nanotechnology can be traced to ancient Greek philosophers while accidental nanotechnology-enabled objects can even be traced to ancient Rome. Many of the field’s luminaries contest claims that one of physicist Richard Feynman’s 1959 lectures is the basis for contemporary nanotechnology.

Here’s the week 2 slide deck:

Week2_history

Here are my ‘notes’ for yesterday’s class consisting largely of brief heads designed to remind me of the content to be found by clicking the link directly after the head.

Week2_Not as new_history

Happy Reading and don’t forget to turn back the clock Saturday night (Nov. 1, 2014) should you live in Canada or the US.

Simon Fraser University – SCFC861Nanotechnology, The Next Big Idea: course Week 1

Yesterday (Oct. 23, 2014) I started teaching a course called, Nanotechnology: The Next Big Idea for Simon Fraser University’s (SFU) Continuing Studies programme and understand that students want a copy of the slides. Unfortunately, SFU does not have a system in place for continuing studies instructors to make their course materials available online to students, so, at the end of this post you will find a link to my Week One PowerPoint slides.

For those who may be mildly curious, here’s a description of the course and of what I was covering in the first week (from SFU’s course description webpage),

Nano what? Well, it’s the manipulation of matter on an atomic, molecular and supra-molecular scale. Considered obscure and still little understood by many outside the scientific community, even the term is contested. Is it nanoscience or nanotechnoogy? The answer is: it depends. It is epxected that nanotechnology will have a greater social impact than computers and the Internet.

We will explore the world of carbon nanotubes, graphene and other nanomaterials; the formal (government) and informatl (popular culture) discussions regarding risks and benefits; and Canada’s place in the international race underway to develop this emerging science and technology.

Week 1: Nanotechnology: The Nitty Gritty

What is nanotechnology? Even scientists have a problem explaining it especially since definitions for it are relatively new and still evolving. We will largely focus on the nature of carbon nanotubes, buckyballs, grapheme and silver/gold nanoparticles as a means of understanding “nanotech.”

Here’s the week 1 slide deck (revised to reflect the material covered during the class):

Week1_definitions and the nitty grittyR

Here are my ‘notes’ for yesterday’s class consisting largely of brief heads designed to remind me of the content to be found by clicking the link directly after the head.

Week1_definitons and nitty gritty

Happy Reading!

Getting up to the size of a dust speck, the first ‘large’ self-assembling DNA crystals

An Oct. 19, 2014 news item on ScienceDaily describes the latest developments in ‘DNA nanotechnology’ research at the Wyss Institute for Biologically Inspired Engineering at Harvard University,

DNA has garnered attention for its potential as a programmable material platform that could spawn entire new and revolutionary nanodevices in computer science, microscopy, biology, and more. Researchers have been working to master the ability to coax DNA molecules to self assemble into the precise shapes and sizes needed in order to fully realize these nanotechnology dreams.

For the last 20 years, scientists have tried to design large DNA crystals with precisely prescribed depth and complex features — a design quest just fulfilled by a team at Harvard’s Wyss Institute for Biologically Inspired Engineering. The team built 32 DNA crystals with precisely-defined depth and an assortment of sophisticated three-dimensional (3D) features, an advance reported in Nature Chemistry.

It seems a bit of a misleading for the Wyss Institute to state the ‘team built’ the DNA crystals as they are self-assembling according to this Oct. 19, 2014 Wyss Institute news release (also on EurekAlert), which originated the news item,

The team used their “DNA-brick self-assembly” method, which was first unveiled in a 2012 Science publication when they created more than 100 3D complex nanostructures about the size of viruses. The newly-achieved periodic crystal structures are more than 1000 times larger than those discrete DNA brick structures, sizing up closer to a speck of dust, which is actually quite large in the world of DNA nanotechnology.

“We are very pleased that our DNA brick approach has solved this challenge,” said senior author and Wyss Institute Core Faculty member Peng Yin, Ph.D., who is also an Associate Professor of Systems Biology at Harvard Medical School, “and we were actually surprised by how well it works.”

The news release goes on to describe some of the issues with other self-assembly methods along with more details about the ‘DNA brick’ approach,

Scientists have struggled to crystallize complex 3D DNA nanostructures using more conventional self-assembly methods. The risk of error tends to increase with the complexity of the structural repeating units and the size of the DNA crystal to be assembled.

The DNA brick method uses short, synthetic strands of DNA that work like interlocking Lego® bricks to build complex structures. Structures are first designed using a computer model of a molecular cube, which becomes a master canvas. Each brick is added or removed independently from the 3D master canvas to arrive at the desired shape – and then the design is put into action: the DNA strands that would match up to achieve the desired structure are mixed together and self assemble to achieve the designed crystal structures.

“Therein lies the key distinguishing feature of our design strategy—its modularity,” said co-lead author Yonggang Ke, Ph.D., formerly a Wyss Institute Postdoctoral Fellow and now an assistant professor at the Georgia Institute of Technology and Emory University. “The ability to simply add or remove pieces from the master canvas makes it easy to create virtually any design.”

The modularity also makes it relatively easy to precisely define the crystal depth. “This is the first time anyone has demonstrated the ability to rationally design crystal depth with nanometer precision, up to 80 nm in this study,” Ke said. In contrast, previous two-dimensional DNA lattices are typically single-layer structures with only 2 nm depth.

“DNA crystals are attractive for nanotechnology applications because they are comprised of repeating structural units that provide an ideal template for scalable design features”, said co-lead author graduate student Luvena Ong.

Furthermore, as part of this study the team demonstrated the ability to position gold nanoparticles into prescribed 2D architectures less than two nanometers apart from each other along the crystal structure – a critical feature for future quantum devices and a significant technical advance for their scalable production, said co-lead author Wei Sun, Ph.D., Wyss Institute Postdoctoral Fellow.

“My preconceived notions of the limitations of DNA have been consistently shattered by our new advances in DNA nanotechnology,” said William Shih, Ph.D., who is co-author of the study and a Wyss Institute Founding Core Faculty member, as well as Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the Dana-Farber Cancer Institute. “DNA nanotechnology now makes it possible for us to assemble, in a programmable way, prescribed structures rivaling the complexity of many molecular machines we see in Nature.”

“Peng’s team is using the DNA-brick self-assembly method to build the foundation for the new landscape of DNA nanotechnology at an impressive pace,” said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “What have been mere visions of how the DNA molecule could be used to advance everything from the semiconductor industry to biophysics are fast becoming realities.”

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

DNA brick crystals with prescribed depths by Yonggang Ke, Luvena L. Ong, Wei Sun, Jie Song, Mingdong Dong, William M. Shih, & Peng Yin. Nature Chemistry (2014) doi:10.1038/nchem.2083 Published online 19 October 2014

This paper is behind a paywall.

Simon Fraser University – Bioelectronics course: Week 6 (the end)

As I noted in my Oct. 7, 2014 posting, I changed up the order of the classes. Last night (Oct. 20, 2014)), I presented the Week 5 material for the last class  of Bioelectronics, Medical Imaging and Our Bodies (at Simon Fraser University in Vancouver, Canada). So, here’s a description of what I presented in this course’s last class,

Week 5 6: Reverse Engineering the Brain and Neuromorphic Engineering

New computer algorithms exploit supercomputing architectures in order to measure the connections between cortical and sub-cortical locations in the human body. While brain repair is one desired outcome, there is also a major interest in developing artificial brains. The boundary between machine and human is breaking down.

I also presented information about the ‘brain in a dish’ mentioned in the session on Growing Human Organs.

Here’s the final week’s slide deck,

Week 5_Reverse & Neuromorphic Engineering

As usual, here are my ‘notes’ for last night’s class consisting largely of brief heads designed to remind me of the content to be found by clicking the link directly after the head.

Week 5 Neuromorphic engineering and brain

Happy Reading! and one final note, I will be teaching a new six-week course at Simon Fraser University : Nanotechnology: The Next Big Idea.  It starts this week on Thursday, Oct. 23, 2014.

Nestling a two-element atomic chain inside a carbon nanotube

While there doesn’t seem to be a short-term application for this research from Japan, the idea of nestling a chain of two elements inside a carbon nanotube is intriguing, from an Oct. 16, 2014 news item on Nanowerk,

Kazutomo Suenaga of the Nanotube Research Center (NTRC) of the National Institute of Advanced Industrial Science and Technology (AIST) and Ryosuke Senga of the Nano-carbon Characterization Team, NTRC, AIST, have synthesized an atomic chain in which two elements are aligned alternately and have evaluated its physical properties on an atomic level.

An ionic crystalline atomic chain of cesium iodine (CsI) has been synthesized by aligning a cesium ion (Cs+), a cation and an iodine ion (I-), an anion, alternately by encapsulating CsI in the microscopic space inside a carbon nanotube. Furthermore, by using an advanced aberration-corrected electron microscope, the physical phenomena unique to the CsI atomic chain, such as the difference in dynamic behavior of its cations and anions, have been discovered. In addition, from theoretical calculation using density functional theory (DFT), this CsI atomic chain has been found to indicate different optical properties from a three-dimensional CsI crystal, and applications to new optical devices are anticipated.

An Oct. 16, 2014 National Institute of Advanced Industrial Science and Technology (AIST) press release, which originated the news item, situates the research within a social and historical context,

Social Background of Research

In the accelerating and ballooning information society, electronic devices used in computers and smartphones has constantly demanded higher performance and efficiency. The materials currently drawing expectations are low-dimensional materials with a single to few-atom width and thickness. Two-dimensional materials, typified by graphene, indicate unique physical characteristics not found in three-dimensional materials, such as its excellent electrical transport properties, and are being extensively researched.

An atomic chain, which has an even finer structure with a width of only one atom, has been predicted to display excellent electrical transport properties, like two-dimensional materials. Although expectations were higher than for two-dimensional materials from the viewpoint of integration, it had attracted little attention until now. This is because of the technological difficulties faced by the various processes of academic research from synthesis to analysis of atomic chains, and academic understanding has not progressed far (Fig. 1).

Figure 1
Figure 1 : Transition of target materials in material research

History of Research

AIST has been developing element analysis methods on a single-atom level to detect certain special structures including impurities, dopants and defects, that affect the properties of low-dimensional materials such as carbon nanotubes and graphene (AIST press releases on July 6, 2009, January 12, 2010, December 16, 2010 and July 9, 2012). In this research, efforts were made for the synthesis and analysis of the atomic chain, a low-dimensional material, using the accumulated technological expertise. This research has been supported by both the Strategic Basic Research Program of the Japan Science and Technology Agency (FY2012 to FY2016), and the Grants-in-aid for Scientific Research of the Japan Society for the Promotion of Science, “Development of elemental technology for the atomic-scale evaluation and application of low-dimensional materials using nano-space” (FY2014 to FY2016).

The press release also offers more details about the research and future applications,

Details of Research

The developed technology is the technology to expose carbon nanotubes, with a diameter of 1 nm or smaller, to CsI vapor to encapsulate CsI in the microscopic space inside the carbon nanotubes, to synthesize an atomic chain in which two elements, Cs and I, are aligned alternately. Furthermore, by combining aberration-corrected electron microscopy and an electronic spectroscopic technique known as electron energy-loss spectroscopy (EELS) detailed structural analysis of this atomic chain was conducted. In order to identify each atom aligned at a distance of 1 nm or less without destroying them, the accelerating voltage of the electron microscope was significantly lowered to 60 kV to reduce damage to the sample by electron beams, while maintaining sufficient spatial resolution of around 1 nm. Figure 2 indicates the smallest CsI crystal confirmed so far, and the CsI atomic chain synthesized in this research.

Figure 2
Figure 2 : Comparison of CsI atomic chain and CsI crystal
(Top: Actual annular dark-field images, Bottom: Corresponding models)

Figure 3 shows the annular dark-field (ADF) image of the CsI atomic chain and the element mapping for Cs and I, respectively, obtained by EELS. It can be seen that the two elements are aligned alternately. There has not been any report of this simple and ideal structure actually being produced and observed, and it can be said to be a fundamental, important finding in material science.

Normally, in an ADF image, those with larger atomic numbers appear brighter. However, in this CsI atomic chain, I (atomic number 53) appears brighter than Cs (atomic number 55). This is because Cs, being a cation, moves more actively (more accurately, the total amount of electrons scattered by the Cs atom is not very different from those of the I atom, but the electrons scattered by the moving Cs atom generate spatial expansion), indicating a difference in dynamic behavior of the cation and the anion that cannot occur in a large three-dimensional crystal. Locations where single Cs atom or I atom is absent, namely vacancies, were also found (Fig. 3, right).

The unique behavior and structure influence various physical properties. When optical absorption spectra were calculated using DFT, the response of the CsI atomic chain to light differed with the direction of incidence. Furthermore, it was found that in a CsI atomic chain with vacancies, the electron state of vacancy sites where the I atom is absent possess a donor level at which electrons were easily released, while vacancy sites where the Cs atom is absent possess a receptor level at which electrons were easily received. By making use of these physical properties, applications to new electro-optical devices, such as a micro-light source and an optical switch using light emission from a single vacancy in the CsI atomic chain, are conceivable. In addition, further research into combinations of other elements triggered by the present results may lead to the development of new materials and device applications. There are expectations for atomic chains to be the next-generation materials for devices in search of further miniaturization and integration.

Figure 3
Figure 3 : Synthesized CsI atomic chain, encapsulated in double-walled carbon nanotube
(From left: ADF image, element maps for Cs and I, model, ADF image of CsI atomic chains with vacancies)

Future Plans

Since the CsI atomic chain displays optical properties significantly different from large crystals that can be seen by the human eye, there are expectations for its application for new electro-optical devices such as a micro-light source and an optical switch using light emission from a single vacancy in the CsI atomic chain. The researchers will conduct experimental research in its application, focused on detailed study of its various physical properties, starting with its optical properties. In addition to CsI, efforts will also be made in the development of new materials that combine various elements, by applying this technology to other materials.

Furthermore, the mechanism of all adsorbents of radioactive substances (carbon nanotubes, zeolite, Prussian blue, etc.) currently being developed for commercial use are methods of encapsulating radioactive atoms inside microscopic space in the material. The researchers hope to utilize the knowledge of the behavior of the Cs atom in a microscopic space obtained in this research, to improve adsorption performance.

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

Atomic structure and dynamic behaviour of truly one-dimensional ionic chains inside ​carbon nanotubes by Ryosuke Senga, Hannu-Pekka Komsa, Zheng Liu, Kaori Hirose-Takai, Arkady V. Krasheninnikov, & Kazu Suenaga. Nature Materials (2014) doi:10.1038/nmat4069 Published online 14 September 2014

This paper is behind a paywall.

Simon Fraser University – Bioelectronics course: Week 5

Last night (Oct. 6, 2014) I changed it up and presented Week 6 of Bioelectronics, Medical Imaging and Our Bodies (at Simon Fraser University in Vancouver, Canada) instead of the previously planned week 5 topic on reverse engineering the brain and neuromorphic engineering, I wanted to encourage students to view a documentary available on Knowledge Network, How to Build a Beating Heart before it disappears from the Knowledge website on Oct. 14, 2014 and our week 6 class on ‘building organs’ wasn’t scheduled until the Monday (Oct. 20, 2014) after Thanksgiving weekend Oct. 11 – 13, 2014.

Last night’s class was on this topic:

Week 6 5: Growing Human Organs

While human organs are being grown or 3D-printed for transplant purposes, they are also being grown on chips for toxicology testing and, in a stunning turn of events, an August 2014 New York Times article described U.S. researchers who grew a “brain in a dish.”‘

Note 1: The ‘brain in a dish’ will be covered in what should have been the week 5 topic so you won’t find it in either the slide deck or the notes for last night’s class.

Note 2: I have kept week 6 in the file names for last night’s class materials (slide presentation and notes) on the assumption that at some point in the future I may go back to this material having forgotten that I switched the weeks around.

Here’s the slide deck for last night’s class:

Week 6_Growing Organs

As usual, here are my ‘notes’ for last night’s class consisting largely of brief heads designed to remind me of the content to be found by clicking the link directly after the head.

Week 6 Organ and human on a chip

Happy Reading!