Tag Archives: Tokyo Institute of Technology

Put a ring on it: preventing clumps of gold nanoparticles

Caption: A comparison of how linear PEG (left) and cyclic PEG (right) attach to a gold nanoparticle Credit: Yubo Wang, Takuya Yamamoto

A January 20, 2021 news item on phys.org focuses on work designed to stop gold nanoparticles from clumping together (Note: A link has been removed),

Hokkaido University scientists have found a way to prevent gold nanoparticles from clumping, which could help towards their use as an anti-cancer therapy.

Attaching ring-shaped synthetic compounds to gold nanoparticles helps them retain their essential light-absorbing properties, Hokkaido University researchers report in the journal Nature Communications.

A January 20, 2021 Hokkaido University press release (also on EurekAlert but published Jan. 21, 2020), which originated the news item, elaborates on the work,

Metal nanoparticles have unique light-absorbing properties, making them interesting for a wide range of optical, electronic and biomedical applications. For example, if delivered to a tumour, they could react with applied light to kill cancerous tissue. A problem with this approach, though, is that they easily clump together in solution, losing their ability to absorb light. This clumping happens in response to a variety of factors, including temperature, salt concentration and acidity.

Scientists have been trying to find ways to ensure nanoparticles stay dispersed in their target environments. Covering them with polyethylene glycol, otherwise known as PEG, has been relatively successful at this in the case of gold nanoparticles. PEG is biocompatible and can prevent gold surfaces from clumping together in the laboratory and in living organisms, but improvements are still needed.

Applied chemist Takuya Yamamoto and colleagues at Hokkaido University, The University of Tokyo, and Tokyo Institute of Technology found that mixing gold nanoparticles with ring-shaped PEG, rather than the normally linear PEG, significantly improved dispersion. The ‘cyclic-PEG’ (c-PEG) attaches to the surfaces of the nanoparticles without forming chemical bonds with them, a process called physisorption. The coated nanoparticles remained dispersed when frozen, freeze-dried and heated.

The team tested the c-PEG-covered gold nanoparticles in mice and found that they cleared slowly from the blood and accumulated better in tumours compared to gold nanoparticles coated with linear PEG. However, accumulation was lower than desired levels, so the researchers recommend further investigations to fine-tune the nanoparticles for this purpose.

Associate Professor Takuya Yamamoto is part of the Laboratory of Chemistry of Molecular Assemblies at Hokkaido University, where he studies the properties and applications of various cyclic chemical compounds.

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

Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol) by Yubo Wang, Jose Enrico Q. Quinsaat, Tomoko Ono, Masatoshi Maeki, Manabu Tokeshi, Takuya Isono, Kenji Tajima, Toshifumi Satoh, Shin-ichiro Sato, Yutaka Miura & Takuya Yamamoto. Nature Communications volume 11, Article number: 6089 (2020) DOI: https://doi.org/10.1038/s41467-020-19947-8 Published: 30 November 2020

This paper is open access.

A deep look at atomic switches

A July 19, 2019 news item on phys.org describes research that may result in a substantive change for information technology,

A team of researchers from Tokyo Institute of Technology has gained unprecedented insight into the inner workings of an atomic switch. By investigating the composition of the tiny metal ‘bridge’ that forms inside the switch, their findings may spur the design of atomic switches with improved performance.

A July 22, 2019 Tokyo Institute of Technology press release (also on EurekAlert but published July 19, 2019), which originated the news item, explains how this research could have such an important impact,

Atomic switches are hailed as the tiniest of electrochemical switches that could change the face of information technology. Due to their nanoscale dimensions and low power consumption, they hold promise for integration into next-generation circuits that could drive the development of artificial intelligence (AI) and Internet of Things (IoT) devices.

Although various designs have emerged, one intriguing question concerns the nature of the metallic filament, or bridge, that is key to the operation of the switch. The bridge forms inside a metal sulfide layer sandwiched between two electrodes [see figure below], and is controlled by applying a voltage that induces an electrochemical reaction. The formation and annihilation of this bridge determines whether the switch is on or off.

Now, a research group including Akira Aiba and Manabu Kiguchi and colleagues at Tokyo Institute of Technology’s Department of Chemistry has found a useful way to examine precisely what the bridge is composed of.

By cooling the atomic switch enough so as to be able to investigate the bridge using a low-temperature measurement technique called point contact spectroscopy (PCS) [2], their study revealed that the bridge is made up of metal atoms from both the electrode and the metal sulfide layer. This surprising finding controverts the prevailing notion that the bridge derives from the electrode only, Kiguchi explains.

The team compared atomic switches with different combinations of electrodes (Pt and Ag, or Pt and Cu) and metal sulfide layers (Cu2S and Ag2S). In both cases, they found that the bridge is mainly composed of Ag.

The reason behind the dominance of Ag in the bridge is likely due to “the higher mobility of Ag ions compared to Cu ions”, the researchers say in their paper published in ACS Applied Materials & Interfaces.

They conclude that “it would be better to use metals with low mobility” for designing atomic switches with higher stability.

Much remains to be explored in the advancement of atomic switch technologies, and the team is continuing to investigate which combination of elements would be the most effective in improving performance.


Technical terms
[1] Atomic switch: The idea behind an atomic switch — one that can be controlled by the motion of a single atom — was introduced by Donald Eigler and colleagues at the IBM Almaden Research Center in 1991. Interest has since focused on how to realize and harness the potential of such extremely small switches for use in logic circuits and memory devices. Over the past two decades, researchers in Japan have taken a world-leading role in the development of atomic switch technologies.
[2] Point contact spectroscopy: A method of measuring the properties or excitations of single atoms at low temperature.

Caption: The ‘bridge’ that forms within the metal sulfide layer, connecting two metal electrodes, results in the atomic switch being turned on. Credit: Manabu Kiguchi

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

Investigation of Ag and Cu Filament Formation Inside the Metal Sulfide Layer of an Atomic Switch Based on Point-Contact Spectroscopy by A. Aiba, R. Koizumi, T. Tsuruoka, K. Terabe, K. Tsukagoshi, S. Kaneko, S. Fujii, T. Nishino, M. Kiguchi. ACS Appl. Mater. Interfaces 2019 XXXXXXXXXX-XXX DOI: https://doi.org/10.1021/acsami.9b05523 Publication Date:July 5, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.

For anyone who might need a bit of a refresher for the chemical elements, Pt is platinum, Ag is silver, and Cu is copper. So, with regard to the metal sulfide layers Cu2S is copper sulfide and Ag2S is silver sulfide.

Periodic table of nanomaterials

This charming illustration is the only pictorial representation i’ve seen for Kyoto University’s (Japan) proposed periodic table of nanomaterials, (By the way, 2019 is UNESCO’s [United Nations Educational, Scientific and Cultural Organization] International Year of the Periodic Table of Elements, an event recognizing the table’s 150th anniversary. See my January 8, 2019 posting for information about more events.)

Caption: Molecules interact and align with each other as they self-assemble. This new simulation enables to find what molecules best interact with each other to build nanomaterials, such as materials that work as a nano electrical wire.
Credit Illustration by Izumi Mindy Takamiya

A July 23, 2018 news item on Nanowerk announces the new periodic table (Note: A link has been removed),

The approach was developed by Daniel Packwood of Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) and Taro Hitosugi of the Tokyo Institute of Technology (Nature Communications, “Materials informatics for self-assembly of functionalized organic precursors on metal surfaces”). It involves connecting the chemical properties of molecules with the nanostructures that form as a result of their interaction. A machine learning technique generates data that is then used to develop a diagram that categorizes different molecules according to the nano-sized shapes they form.

This approach could help materials scientists identify the appropriate molecules to use in order to synthesize target nanomaterials.

A July 23, 2018 Kyoto University press release on EurekAlert, which originated the news item, explains further about the computer simulations run by the scientists in pursuit of their specialized periodic table,

Fabricating nanomaterials using a bottom-up approach requires finding ‘precursor molecules’ that interact and align correctly with each other as they self-assemble. But it’s been a major challenge knowing how precursor molecules will interact and what shapes they will form.

Bottom-up fabrication of graphene nanoribbons is receiving much attention due to their potential use in electronics, tissue engineering, construction, and bio-imaging. One way to synthesise them is by using bianthracene precursor molecules that have bromine ‘functional’ groups attached to them. The bromine groups interact with a copper substrate to form nano-sized chains. When these chains are heated, they turn into graphene nanoribbons.

Packwood and Hitosugi tested their simulator using this method for building graphene nanoribbons.

Data was input into the model about the chemical properties of a variety of molecules that can be attached to bianthracene to ‘functionalize’ it and facilitate its interaction with copper. The data went through a series of processes that ultimately led to the formation of a ‘dendrogram’.

This showed that attaching hydrogen molecules to bianthracene led to the development of strong one-dimensional nano-chains. Fluorine, bromine, chlorine, amidogen, and vinyl functional groups led to the formation of moderately strong nano-chains. Trifluoromethyl and methyl functional groups led to the formation of weak one-dimensional islands of molecules, and hydroxide and aldehyde groups led to the formation of strong two-dimensional tile-shaped islands.

The information produced in the dendogram changed based on the temperature data provided. The above categories apply when the interactions are conducted at -73°C. The results changed with warmer temperatures. The researchers recommend applying the data at low temperatures where the effect of the functional groups’ chemical properties on nano-shapes are most clear.

The technique can be applied to other substrates and precursor molecules. The researchers describe their method as analogous to the periodic table of chemical elements, which groups atoms based on how they bond to each other. “However, in order to truly prove that the dendrograms or other informatics-based approaches can be as valuable to materials science as the periodic table, we must incorporate them in a real bottom-up nanomaterial fabrication experiment,” the researchers conclude in their study published in the journal xxx. “We are currently pursuing this direction in our laboratories.”

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

Materials informatics for self-assembly of functionalized organic precursors on metal surfaces by Daniel M. Packwood & Taro Hitosugi. Nature Communicationsvolume 9, Article number: 2469 (2018)DOI: https://doi.org/10.1038/s41467-018-04940-z Published 25 June 2018

This paper is open access.


It’s a bit of a stretch but I really appreciate how the nanoscale (specifically a fullerene) is being paired with the second largest planet (the largest is Jupiter) in our solar system. (See Nola Taylor Redd’s November 14, 2012 article on space.com for more about the planet Saturn.)

From a June 8, 2018 news item on ScienceDaily,

Saturn is the second largest planet in our solar system and has a characteristic ring. Japanese researchers have now synthesized a molecular “nano-Saturn.” As the scientists report in the journal Angewandte Chemie, it consists of a spherical C(60) fullerene as the planet and a flat macrocycle made of six anthracene units as the ring. The structure is confirmed by spectroscopic and X-ray analyses.

A June 8, 2018  Wiley Publications press release (also on EurekAlert), which originated the news item, fills in some details,

Nano-Saturn systems with a spherical molecule and a macrocyclic ring have been a fascinating structural motif for researchers. The ring must have a rigid, circular form, and must hold the molecular sphere firmly in its midst. Fullerenes are ideal candidates for the nano-sphere. They are made of carbon atoms linked into a network of rings that form a hollow sphere. The most famous fullerene, C60, consists of 60 carbon atoms arranged into 5- and 6-membered rings like the leather patches of a classic soccer ball. The electrons in their double bonds, knows as the π-electrons, are in a kind of “electron cloud”, able to freely move about and have binding interactions with other molecules, such as a macrocycle that also has a “cloud” of π-electrons. The attractive interactions between the electron clouds allow fullerenes to lodge in the cavities of such macrocycles.

A series of such complexes has previously been synthesized. Because of the positions of the electron clouds around the macrocycles, it was previously only possible to make rings that surround the fullerene like a belt or a tire. The ring around Saturn, however, is not like a “belt” or “tire”, it is a very flat disc. Researchers working at the Tokyo Institute of Technology and Okayama University of Science (Japan) wanted to properly imitate this at nanoscale.

Their success resulted from a different type of bonding between the “nano-planet” and its “nano-ring”. Instead of using the attraction between the π-electron clouds of the fullerene and macrocycle, the team working with Shinji Toyota used the weak attractive interactions between the π-electron cloud of the fullerene and non- π-electron of the carbon-hydrogen groups of the macrocycle.

To construct their “Saturn ring”, the researchers chose to use anthracene units, molecules made of three aromatic six-membered carbon rings linked along their edges. They linked six of these units into a macrocycle whose cavity was the perfect size and shape for a C60 fullerene. Eighteen hydrogen atoms of the macrocycle project into the middle of the cavity. In total, their interactions with the fullerene are enough to give the complex enough stability, as shown by computer simulations. By using X-ray analysis and NMR spectroscopy, the team was able to prove experimentally that they had produced Saturn-shaped complexes.

Here’s an illustration of the ‘nano-saturn’,

Courtesy: Wiley Publications

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

Nano‐Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60 by Yuta Yamamoto, Dr. Eiji Tsurumaki, Prof. Dr. Kan Wakamatsu, Prof. Dr. Shinji Toyota. Angewandte Chemie https://doi.org/10.1002/anie.201804430 First published: 30 May 2018

This paper is behind a paywall.

nano tech 2017 being held in Tokyo from February 15-17, 2017

I found some news about the Alberta technology scene in the programme for Japan’s nano tech 2017 exhibition and conference to be held Feb. 15 – 17, 2017 in Tokyo. First, here’s more about the show in Japan from a Jan. 17, 2017 nano tech 2017 press release on Business Wire (also on Yahoo News),

The nano tech executive committee (chairman: Tomoji Kawai, Specially Appointed Professor, Osaka University) will be holding “nano tech 2017” – one of the world’s largest nanotechnology exhibitions, now in its 16th year – on February 15, 2017, at the Tokyo Big Sight convention center in Japan. 600 organizations (including over 40 first-time exhibitors) from 23 countries and regions are set to exhibit at the event in 1,000 booths, demonstrating revolutionary and cutting edge core technologies spanning such industries as automotive, aerospace, environment/energy, next-generation sensors, cutting-edge medicine, and more. Including attendees at the concurrently held exhibitions, the total number of visitors to the event is expected to exceed 50,000.

The theme of this year’s nano tech exhibition is “Open Nano Collaboration.” By bringing together organizations working in a wide variety of fields, the business matching event aims to promote joint development through cross-field collaboration.

Special Symposium: “Nanotechnology Contributing to the Super Smart Society”

Each year nano tech holds Special Symposium, in which industry specialists from top organizations from Japan and abroad speak about the issues surrounding the latest trends in nanotech. The themes of this year’s Symposium are Life Nanotechnology, Graphene, AI/IoT, Cellulose Nanofibers, and Materials Informatics.

Notable sessions include:

Life Nanotechnology
“Development of microRNA liquid biopsy for early detection of cancer”
Takahiro Ochiya, National Cancer Center Research Institute Division of Molecular and Cellular Medicine, Chief

AI / IoT
“AI Embedded in the Real World”
Hideki Asoh, AIST Deputy Director, Artificial Intelligence Research Center

Cellulose Nanofibers [emphasis mine]
“The Current Trends and Challenges for Industrialization of Nanocellulose”
Satoshi Hirata, Nanocellulose Forum Secretary-General

Materials Informatics
“Perspective of Materials Research”
Hideo Hosono, Tokyo Institute of Technology Professor

View the full list of sessions:
>> http://nanotech2017.icsbizmatch.jp/Presentation/en/Info/List#main_theater

nano tech 2017 Homepage:
>> http://nanotechexpo.jp/

nano tech 2017, the 16th International Nanotechnology Exhibition & Conference
Date: February 15-17, 2017, 10:00-17:00
Venue: Tokyo Big Sight (East Halls 4-6 & Conference Tower)
Organizer: nano tech Executive Committee, JTB Communication Design

As you may have guessed the Alberta information can be found in the .Cellulose Nanofibers session. From the conference/seminar program page; scroll down about 25% of the way to find the Alberta presentation,

Production and Applications Development of Cellulose Nanocrystals (CNC) at InnoTech Alberta

Behzad (Benji) Ahvazi
InnoTech Alberta Team Lead, Cellulose Nanocrystals (CNC)

[ Abstract ]

The production and use of cellulose nanocrystals (CNC) is an emerging technology that has gained considerable interest from a range of industries that are working towards increased use of “green” biobased materials. The construction of one-of-a-kind CNC pilot plant [emphasis mine] at InnoTech Alberta and production of CNC samples represents a critical step for introducing the cellulosic based biomaterials to industrial markets and provides a platform for the development of novel high value and high volume applications. Major key components including feedstock, acid hydrolysis formulation, purification, and drying processes were optimized significantly to reduce the operation cost. Fully characterized CNC samples were provided to a large number of academic and research laboratories including various industries domestically and internationally for applications development.

[ Profile ]

Dr. Ahvazi completed his Bachelor of Science in Honours program at the Department of Chemistry and Biochemistry and graduated with distinction at Concordia University in Montréal, Québec. His Ph.D. program was completed in 1998 at McGill Pulp and Paper Research Centre in the area of macromolecules with solid background in Lignocellulosic, organic wood chemistry as well as pulping and paper technology. After completing his post-doctoral fellowship, he joined FPInnovations formally [formerly?] known as PAPRICAN as a research scientist (R&D) focusing on a number of confidential chemical pulping and bleaching projects. In 2006, he worked at Tembec as a senior research scientist and as a Leader in Alcohol and Lignin (R&D). In April 2009, he held a position as a Research Officer in both National Bioproducts (NBP1 & NBP2) and Industrial Biomaterials Flagship programs at National Research Council Canada (NRC). During his tenure, he had directed and performed innovative R&D activities within both programs on extraction, modification, and characterization of biomass as well as polymer synthesis and formulation for industrial applications. Currently, he is working at InnoTech Alberta as Team Lead for Biomass Conversion and Processing Technologies.

Canada scene update

InnoTech Alberta was until Nov. 1, 2016 known as Alberta Innovates – Technology Futures. Here’s more about InnoTech Alberta from the Alberta Innovates … home page,

Effective November 1, 2016, Alberta Innovates – Technology Futures is one of four corporations now consolidated into Alberta Innovates and a wholly owned subsidiary called InnoTech Alberta.

You will find all the existing programs, services and information offered by InnoTech Alberta on this website. To access the basic research funding and commercialization programs previously offered by Alberta Innovates – Technology Futures, explore here. For more information on Alberta Innovates, visit the new Alberta Innovates website.

As for InnoTech Alberta’s “one-of-a-kind CNC pilot plant,” I’d like to know more about it’s one-of-a-kind status since there are two other CNC production plants in Canada. (Is the status a consequence of regional chauvinism or a writer unfamiliar with the topic?). Getting back to the topic, the largest company (and I believe the first) with a CNC plant was CelluForce, which started as a joint venture between Domtar and FPInnovations and powered with some very heavy investment from the government of Canada. (See my July 16, 2010 posting about the construction of the plant in Quebec and my June 6, 2011 posting about the newly named CelluForce.) Interestingly, CelluForce will have a booth at nano tech 2017 (according to its Jan. 27, 2017 news release) although the company doesn’t seem to have any presentations on the schedule. The other Canadian company is Blue Goose Biorefineries in Saskatchewan. Here’s more about Blue Goose from the company website’s home page,

Blue Goose Biorefineries Inc. (Blue Goose) is pleased to introduce our R3TM process. R3TM technology incorporates green chemistry to fractionate renewable plant biomass into high value products.

Traditionally, separating lignocellulosic biomass required high temperatures, harsh chemicals, and complicated processes. R3TM breaks this costly compromise to yield high quality cellulose, lignin and hemicellulose products.

The robust and environmentally friendly R3TM technology has numerous applications. Our current product focus is cellulose nanocrystals (CNC). Cellulose nanocrystals are “Mother Nature’s Building Blocks” possessing unique properties. These unique properties encourage the design of innovative products from a safe, inherently renewable, sustainable, and carbon neutral resource.

Blue Goose assists companies and research groups in the development of applications for CNC, by offering CNC for sale without Intellectual Property restrictions. [emphasis mine]

Bravo to Blue Goose! Unfortunately, I was not able to determine if the company will be at nano tech 2017.

One final comment, there was some excitement about CNC a while back where I had more than one person contact me asking for information about how to buy CNC. I wasn’t able to be helpful because there was, apparently, an attempt by producers to control sales and limit CNC access to a select few for competitive advantage. Coincidentally or not, CelluForce developed a stockpile which has persisted for some years as I noted in my Aug. 17, 2016 posting (scroll down about 70% of the way) where the company announced amongst other events that it expected deplete its stockpile by mid-2017.

pH dependent nanoparticle-based contrast agent for MRIs (magnetic resonance images)

This news about a safer and more effective contrast agent for MRIs (magnetic resonance images) developed by Japanese scientists come from a June 6, 2016 article by Heather Zeiger on phys.org. First some explanations,

Magnetic resonance imaging relies on the excitation and subsequent relaxation of protons. In clinical MRI studies, the signal is determined by the relaxation time of the hydrogen protons in water. To get a stronger signal, scientists can use contrast agents to shorten the relaxation time of the protons.

MRI is non-invasive and does not involve radiation, making it a safe diagnostic tool. However, its weak signal makes tumor detection difficult. The ideal contrast agent would select for malignant tumors, making its location and diagnosis much more obvious.

Nanoparticle contrast agents have been of interested because nanoparticles can be functionalized and, as in this study, can contain various metals. Researchers have attempted to functionalize nanoparticles with ligands that attach to chemical factors on the surface of cancer cells. However, cancer cells tend to be compositionally heterogeneous, leading some researchers to look for nanoparticles that respond to differences in pH or redox potential compared to normal cells.

Now for the research,

Researchers from the University of Tokyo, Tokyo Institute of Technology, Kawasaki Institute of Industry Promotion, and the Japan Agency for Quantum and Radiological Science and Technology have developed a contrast agent from calcium phosphate-based nanoparticles that release a manganese ion an acidic environment. …

Peng Mi, Daisuke Kokuryo, Horacio Cabral, Hailiang Wu, Yasuko Terada, Tsuneo Saga, Ichio Aoki, Nobuhiro Nishiyama, and Kazunori Kataoka developed a contrast agent that is comprised of Mn2+– doped CaP nanoparticles with a PEG shell. They reasoned that using CaP nanoparticles, which are known to be pH sensitive, would allow the targeted release of Mn2+ ions in the tumor microenvironment. The tumor microenvironment tends to have a lower pH than the normal regions to rapid cell metabolism in an oxygen-depleted environment. Manganese ions were tested because they are paramagnetic, which makes for a good contrast agent. They also bind to proteins creating a slowly rotating manganese-protein system that results in sharp contrast enhancement.

These results were promising, so Peng Mi, et al. then tested whether the CaPMnPEG contrast agent worked in solid tumors. Because Mn2+ remains confined within the nanoparticle matrix at physiological pH, CaPMnPEG demonstrate a much lower toxicity [emphasis mine] compared to MnCl2. MRI studies showed a tumor-to-normal contrast of 131% after 30 minute, which is much higher than Gd-DTPA [emphasis mine], a clinically approved contrast agent. After an hour, the tumor-to-normal ratio was 160% and remained around 170% for several hours.

Three-dimensional MRI studies of solid tumors showed that without the addition of CaPMnPEG, only blood vessels were visible. However, upon adding CaPMnPEG, the tumor was easily distinguishable. Additionally, there is evidence that excess Mn2+ leaves the plasma after an hour. The contrast signal remained strong for several hours indicating that protein binding rather than Mn2+ concentration is important for signal enhancement.

Finally, tests with metastatic tumors in the liver (C26 colon cancer cells) showed that CaPMnPEG works well in solid organ analysis and is highly sensitive to detecting millimeter-sized micrometastasis [emphasis mine]. Unlike other contrast agents used in the clinic, CaPMnPEG provided a contrast signal that lasted for several hours after injection. After an hour, the signal was enhanced by 25% and after two hours, the signal was enhanced by 39%.

This is exciting stuff. Bravo to the researchers!

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

A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy by Peng Mi, Daisuke Kokuryo, Horacio Cabral, Hailiang Wu, Yasuko Terada, Tsuneo Saga, Ichio Aoki, Nobuhiro Nishiyama, & Kazunori Kataoka. Nature Nanotechnology (2016) doi:10.1038/nnano.2016.72 Published online 16 May 2016

This paper is behind a paywall.

Ingestible origami robot gets one step closer

Fiction, more or less seriously, has been exploring the idea of ingestible, tiny robots that can enter the human body for decades (Fantastic Voyage and Innerspace are two movie examples). The concept is coming closer to being realized as per a May 12, 2016 news item on phys.org,

In experiments involving a simulation of the human esophagus and stomach, researchers at MIT [Massachusetts Institute of Technology], the University of Sheffield, and the Tokyo Institute of Technology have demonstrated a tiny origami robot that can unfold itself from a swallowed capsule and, steered by external magnetic fields, crawl across the stomach wall to remove a swallowed button battery or patch a wound.

A May 12, 2016 MIT news release (also on EurekAlert), which originated the news item, provides some fascinating depth to this story (Note: Links have been removed),

The new work, which the researchers are presenting this week at the International Conference on Robotics and Automation, builds on a long sequence of papers on origami robots from the research group of Daniela Rus, the Andrew and Erna Viterbi Professor in MIT’s Department of Electrical Engineering and Computer Science.

“It’s really exciting to see our small origami robots doing something with potential important applications to health care,” says Rus, who also directs MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL). “For applications inside the body, we need a small, controllable, untethered robot system. It’s really difficult to control and place a robot inside the body if the robot is attached to a tether.”

Although the new robot is a successor to one reported at the same conference last year, the design of its body is significantly different. Like its predecessor, it can propel itself using what’s called a “stick-slip” motion, in which its appendages stick to a surface through friction when it executes a move, but slip free again when its body flexes to change its weight distribution.

Also like its predecessor — and like several other origami robots from the Rus group — the new robot consists of two layers of structural material sandwiching a material that shrinks when heated. A pattern of slits in the outer layers determines how the robot will fold when the middle layer contracts.

Material difference

The robot’s envisioned use also dictated a host of structural modifications. “Stick-slip only works when, one, the robot is small enough and, two, the robot is stiff enough,” says Guitron [Steven Guitron, a graduate student in mechanical engineering]. “With the original Mylar design, it was much stiffer than the new design, which is based on a biocompatible material.”

To compensate for the biocompatible material’s relative malleability, the researchers had to come up with a design that required fewer slits. At the same time, the robot’s folds increase its stiffness along certain axes.

But because the stomach is filled with fluids, the robot doesn’t rely entirely on stick-slip motion. “In our calculation, 20 percent of forward motion is by propelling water — thrust — and 80 percent is by stick-slip motion,” says Miyashita [Shuhei Miyashita, who was a postdoc at CSAIL when the work was done and is now a lecturer in electronics at the University of York, England]. “In this regard, we actively introduced and applied the concept and characteristics of the fin to the body design, which you can see in the relatively flat design.”

It also had to be possible to compress the robot enough that it could fit inside a capsule for swallowing; similarly, when the capsule dissolved, the forces acting on the robot had to be strong enough to cause it to fully unfold. Through a design process that Guitron describes as “mostly trial and error,” the researchers arrived at a rectangular robot with accordion folds perpendicular to its long axis and pinched corners that act as points of traction.

In the center of one of the forward accordion folds is a permanent magnet that responds to changing magnetic fields outside the body, which control the robot’s motion. The forces applied to the robot are principally rotational. A quick rotation will make it spin in place, but a slower rotation will cause it to pivot around one of its fixed feet. In the researchers’ experiments, the robot uses the same magnet to pick up the button battery.

Porcine precedents

The researchers tested about a dozen different possibilities for the structural material before settling on the type of dried pig intestine used in sausage casings. “We spent a lot of time at Asian markets and the Chinatown market looking for materials,” Li [Shuguang Li, a CSAIL postdoc] says. The shrinking layer is a biodegradable shrink wrap called Biolefin.

To design their synthetic stomach, the researchers bought a pig stomach and tested its mechanical properties. Their model is an open cross-section of the stomach and esophagus, molded from a silicone rubber with the same mechanical profile. A mixture of water and lemon juice simulates the acidic fluids in the stomach.

Every year, 3,500 swallowed button batteries are reported in the U.S. alone. Frequently, the batteries are digested normally, but if they come into prolonged contact with the tissue of the esophagus or stomach, they can cause an electric current that produces hydroxide, which burns the tissue. Miyashita employed a clever strategy to convince Rus that the removal of swallowed button batteries and the treatment of consequent wounds was a compelling application of their origami robot.

“Shuhei bought a piece of ham, and he put the battery on the ham,” Rus says. [emphasis mine] “Within half an hour, the battery was fully submerged in the ham. So that made me realize that, yes, this is important. If you have a battery in your body, you really want it out as soon as possible.”

“This concept is both highly creative and highly practical, and it addresses a clinical need in an elegant way,” says Bradley Nelson, a professor of robotics at the Swiss Federal Institute of Technology Zurich. “It is one of the most convincing applications of origami robots that I have seen.”

I wonder if they ate the ham afterwards.

Happily, MIT has produced a video featuring this ingestible, origami robot,

Finally, this team has a couple more members than the previously mentioned Rus, Miyashita, and Li,

…  Kazuhiro Yoshida of Tokyo Institute of Technology, who was visiting MIT on sabbatical when the work was done; and Dana Damian of the University of Sheffield, in England.

As Rus notes in the video, the next step will be in vivo (animal) studies.

Smectic liquid crystals

From an April 10, 2015 news release from the Tokyo Institute of Technology,

Researchers at Tokyo Institute of Technology have designed a smectic liquid crystal that overcomes many of the challenges posed by organic field effect transistor materials.

Crystalline organic semiconductors have attracted a lot of interest for convenient low-cost fabrication by printed electronics. However progress has been stymied by the low thermal durability and reproducibility of these materials. Now researchers at Tokyo Institute of Technology and the Japan Science and Technology Agency have designed a liquid crystal molecule that produces high-performance organic field effect transistors (FETs) with good temperature resilience and relatively low device variability in addition to high mobility.

Hiroaki Iino, Takayuki Usui and Jun-ichi Hanna designed a molecule that would incorporate a number of desirable liquid crystal qualities, in particular the smectic E phase. Low ordered liquid crystal phases form droplets at their melting temperature, but the smectic E phase has the advantage of retaining the thin-film shape.

They then fabricated organic FETs by spin coating a solution of their material at 110 °C before allowing it to cool. Comparison of the FET characteristics before and after mild annealing revealed a phase transition. Using atomic force microscopy the researchers identified that at around 120°C in the crystal formed a bilayer crystal phase.

The mobility of a bottom gated FET made from the material was around 12 cm2V-1s-1 comparable to single-crystal devices. “Considering that it could potentially be necessary to fabricate millions of FETs for display applications, polycrystalline OFETs may have an advantage over single-crystal OFETs,” point out the researchers in a report of the work. The devices also exhibited a minimal variability of just 1.2 cm2V-1s-1, which is likely an advantage from the smoothness of the obtained film.

The researchers conclude, “The discovery of a dramatic enhancement of FET mobility up to 13.9cm2V-1s-1, resulting from the phase transition from a monolayer to a bilayer crystal structure in mono-alkylated liquid crystalline molecules may lead to the possibility of designing new materials for the burgeoning field of printed electronics.”


Small-molecule versus polymer FETs

The main issues around organic semiconductor FETs with small molecules are the low thermal durability. The same bonding that makes the molecules soluble for printing fabrication processes also leaves them prone to low melting points, which greatly inhibits the methods available for processing the materials. They also tend to form rough surfaces, which makes it difficult to reproducibly fabricate the devices that have the desired characteristics.

Attempts to use polymers with benzene-like delocalised electron bonding alleviated issues around the thermal durability to a certain extent. However, it exacerbated others, such as reproducible synthesis and purification of the polymers, as well as control of crystallinity and the molecular orientations towards both the substrate surface and the electrodes.

The design of the molecule

The researchers identified specific characteristics to enrol in the design of their molecule. They used a fused ring system of molecules with benzene-like delocalised electron bonding so that the material would readily crystallise. They then added a phenyl group to introduce the kind of disorder required for smectic E phase liquid crystals. A long flexible carbon chain was also added to encourage formation of a liquid crystal.

The molecule was also designed to have a single side chain so that crystallisation on cooling would be lower than that on heating. This is more convenient for fabrication processes with the material.

The phase transition

Studies of the field effect transistors before and after mild annealing revealed an improvement in carrier mobility by over an order of magnitude. The researchers concluded that the material underwent a phase transition between 70 °C and 120 °C. Improvements in device performance plateaued above 120 °C.

Atomic force microscope studies of the materials identified a step structure that changed from monolayer 2.8 nm steps to bilayer 5.7 nm steps following the phase transition. In the absence of a change in grain size or contact resistance, the researchers concluded that  crystal-to-crystal phase change from a monolayer to a bilayer structure was responsible for the improved transistor performance in annealed devices.

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

Liquid crystals for organic thin-film transistors by Hiroaki Iino, Takayuki Usui & Jun-ichi Hanna. Nature Communications 6, Article number: 6828 doi:10.1038/ncomms7828 Published 10 April 2015

This is an open access paper.

A city of science in Japan: Kawasaki (Kanagawa)

Happily, I’m getting more nanotechnology (for the most part) information from Japan. Given Japan’s prominence in this field of endeavour I’ve long felt FrogHeart has not adequately represented Japanese contributions. Now that I’m receiving English language translations, I hope to better address the situation.

This morning (March 26, 2015), there were two news releases from Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), Coastal Area International Strategy Office, Kawasaki City, Japan in my mailbox. Before getting on to the news releases, here’s a little about  the city of Kawasaki and about its innovation gateway. From the Kawasaki, Kanagawa entry in Wikipedia (Note: Links have been removed),

Kawasaki (川崎市 Kawasaki-shi?) is a city in Kanagawa Prefecture, Japan, located between Tokyo and Yokohama. It is the 9th most populated city in Japan and one of the main cities forming the Greater Tokyo Area and Keihin Industrial Area.

Kawasaki occupies a belt of land stretching about 30 kilometres (19 mi) along the south bank of the Tama River, which divides it from Tokyo. The eastern end of the belt, centered on JR Kawasaki Station, is flat and largely consists of industrial zones and densely built working-class housing, the Western end mountainous and more suburban. The coastline of Tokyo Bay is occupied by vast heavy industrial complexes built on reclaimed land.

There is a 2014 video about Kawasaki’s innovation gateway, which despite its 14 mins. 39 secs. running time I am embedding here. (Caution: They highlight their animal testing facility at some length.)

Now on to the two news releases. The first concerns research on gold nanoparticles that was published in 2014. From a March 26, 2015 Kawasaki INnovation Gateway news release,

Gold nanoparticles size up to cancer treatment

Incorporating gold nanoparticles helps optimise treatment carrier size and stability to improve delivery of cancer treatment to cells.

Treatments that attack cancer cells through the targeted silencing of cancer genes could be developed using small interfering RNA molecules (siRNA). However delivering the siRNA into the cells intact is a challenge as it is readily degraded by enzymes in the blood and small enough to be eliminated from the blood stream by kidney filtration.  Now Kazunori Kataoka at the University of Tokyo and colleagues at Tokyo Institute of Technology have designed a protective treatment delivery vehicle with optimum stability and size for delivering siRNA to cells.

The researchers formed a polymer complex with a single siRNA molecule. The siRNA-loaded complex was then bonded to a 20 nm gold nanoparticle, which thanks to advances in synthesis techniques can be produced with a reliably low size distribution. The resulting nanoarchitecture had the optimum overall size – small enough to infiltrate cells while large enough to accumulate.

In an assay containing heparin – a biological anti-coagulant with a high negative charge density – the complex was found to release the siRNA due to electrostatic interactions. However when the gold nanoparticle was incorporated the complex remained stable. Instead, release of the siRNA from the complex with the gold nanoparticle could be triggered once inside the cell by the presence of glutathione, which is present in high concentrations in intracellular fluid. The glutathione bonded with the gold nanoparticles and the complex, detaching them from each other and leaving the siRNA prone to release.

The researchers further tested their carrier in a subcutaneous tumour model. The authors concluded that the complex bonded to the gold nanoparticle “enabled the efficient tumor accumulation of siRNA and significant in vivo gene silencing effect in the tumor, demonstrating the potential for siRNA-based cancer therapies.”

The news release provides links to the March 2015 newsletter which highlights this research and to the specific article and video,

March 2015 Issue of Kawasaki SkyFront iNewsletter: http://inewsletter-king-skyfront.jp/en/


Feature video on Professor Kataoka’s research : http://inewsletter-king-skyfront.jp/en/video_feature/vol_3/feature01/

Research highlights: http://inewsletter-king-skyfront.jp/en/research_highlights/vol_3/research01/

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

Precise Engineering of siRNA Delivery Vehicles to Tumors Using Polyion Complexes and Gold Nanoparticles by Hyun Jin Kim, Hiroyasu Takemoto, Yu Yi, Meng Zheng, Yoshinori Maeda, Hiroyuki Chaya, Kotaro Hayashi, Peng Mi, Frederico Pittella, R. James Christie, Kazuko Toh, Yu Matsumoto, Nobuhiro Nishiyama, Kanjiro Miyata, and Kazunori Kataoka. ACS Nano, 2014, 8 (9), pp 8979–8991 DOI: 10.1021/nn502125h Publication Date (Web): August 18, 2014
Copyright © 2014 American Chemical Society

This article is behind a paywall.

The second March 26, 2015 Kawasaki INnovation Gateway news release concerns a DNA chip and food-borne pathogens,

Rapid and efficient DNA chip technology for testing 14 major types of food borne pathogens

Conventional methods for testing food-borne pathogens is based on the cultivation of pathogens, a process that is complicated and time consuming. So there is demand for alternative methods to test for food-borne pathogens that are simpler, quick and applicable to a wide range of potential applications.

Now Toshiba Ltd and Kawasaki City Institute for Public Health have collaborated in the development of a rapid and efficient automatic abbreviated DNA detection technology that can test for 14 major types of food borne pathogens. The so called ‘DNA chip card’ employs electrochemical DNA chips and overcomes the complicated procedures associated with genetic testing of conventional methods. The ‘DNA chip card’ is expected to find applications in hygiene management in food manufacture, pharmaceuticals, and cosmetics.


The so-called automatic abbreviated DNA detection technology ‘DNA chip card’ was developed by Toshiba Ltd and in a collaboration with Kawasaki City Institute for Public Health, used to simultaneously detect 14 different types of food-borne pathogens in less than 90 minutes. The detection sensitivity depends on the target pathogen and has a range of 1E+01~05 cfu/mL.

Notably, such tests would usually take 4-5 days using conventional methods based on pathogen cultivation. Furthermore, in contrast to conventional DNA protocols that require high levels of skill and expertise, the ‘DNA chip card’ only requires the operator to inject nucleic acid, thereby making the procedure easier to use and without specialized operating skills.

Examples of pathogens associated with food poisoning that were tested with the “DNA chip card”

Enterohemorrhagic Escherichia coli



Vibrio parahaemolyticus


Staphylococcus aureus

Enterotoxigenic Escherichia coli

Enteroaggregative Escherichia coli

Enteropathogenic Escherichia coli

Clostridium perfringens

Bacillus cereus



Vibrio cholerae

I think 14 is the highest number of tests I’ve seen for one of these chips. This chip is quite an achievement.

One final bit from the news release about the DNA chip provides a brief description of the gateway and something they call King SkyFront,


The Kawasaki INnovation Gateway (KING) SKYFRONT is the flagship science and technology innovation hub of Kawasaki City. KING SKYFRONT is a 40 hectare area located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International Airport (also often referred to as Haneda Airport).

KING SKYFRONT was launched in 2013 as a base for scholars, industrialists and government administrators to work together to devise real life solutions to global issues in the life sciences and environment.

I find this emphasis on the city interesting. It seems that cities are becoming increasingly important and active where science research and development are concerned. Europe seems to have adopted a biannual event wherein a city is declared a European City of Science in conjunction with the EuroScience Open Forum (ESOF) conferences. The first such city was Dublin in 2012 (I believe the Irish came up with the concept themselves) and was later adopted by Copenhagen for 2014. The latest city to embrace the banner will be Manchester in 2016.

Should October 2013 be called ‘the month of graphene’?

Since the Oct. 10-11, 2013 Graphene Flagship (1B Euros investment) launch, mentioned in my preview Oct. 7, 2013 posting, there’ve been a flurry of graphene-themed news items both on this blog and elsewhere and I’ve decided to offer a brief roundup what I’ve found elsewhere.

Dexter Johnson offers a commentary in the pithily titled, Europe Invests €1 Billion to Become “Graphene Valley,” an Oct. 15, 2013 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website) Note: Links have been removed,

The initiative has been dubbed “The Graphene Flagship,” and apparently it is the first in a number of €1 billion, 10-year plans the EC is planning to launch. The graphene version will bring together 76 academic institutions and industrial groups from 17 European countries, with an initial 30-month-budget of €54M ($73 million).

Graphene research is still struggling to find any kind of applications that will really take hold, and many don’t expect it will have a commercial impact until 2020. What’s more, manufacturing methods are still undeveloped. So it would appear that a 10-year plan is aimed at the academic institutions that form the backbone of this initiative rather than commercial enterprises.

Just from a political standpoint the choice of Chalmers University in Sweden as the base of operations for the Graphene Flagship is an intriguing choice. …

I have to agree with Dexter that choosing Chalmers University over the University of Manchester where graphene was first isolated is unexpected. As a companion piece to reading Dexter’s posting in its entirety and which features a video from the flagship launch, you might want to try this Oct. 15, 2013 article by Koen Mortelmans for Youris (h/t Oct. 15, 2013 news item on Nanowerk),

Andre Konstantin Geim is the only person who ever received both a Nobel and an Ig Nobel. He was born in 1958 in Russia, and is a Dutch-British physicist with German, Polish, Jewish and Ukrainian roots. “Having lived and worked in several European countries, I consider myself European. I don’t believe that any further taxonomy is necessary,” he says. He is now a physics professor at the University of Manchester. …

He shared the Noble [Nobel] Prize in 2010 with Konstantin Novoselov for their work on graphene. It was following on their isolation of microscope visible grapheme flakes that the worldwide research towards practical applications of graphene took off.  “We did not invent graphene,” Geim says, “we only saw what was laid up for five hundred year under our noses.”

Geim and Novoselov are often thought to have succeeded in separating graphene from graphite by peeling it off with ordinary duct tape until there only remained a layer. Graphene could then be observed with a microscope, because of the partial transparency of the material. That is, after dissolving the duct tape material in acetone, of course. That is also the story Geim himself likes to tell.

However, he did not use – as the urban myth goes – graphite from a common pencil. Instead, he used a carbon sample of extreme purity, specially imported. He also used ultrasound techniques. But, probably the urban legend will survive, as did Archimedes’ bath and Newtons apple. “It is nice to keep some of the magic,” is the expression Geim often uses when he does not want a nice story to be drowned in hard facts or when he wants to remain discrete about still incomplete, but promising research results.

Mortelmans’ article fills in some gaps for those not familiar with the graphene ‘origins’ story while Tim Harper’s July 22, 2012 posting on Cientifica’s (an emerging technologies consultancy where Harper is the CEO and founder) TNT blog offers an insight into Geim’s perspective on the race to commercialize graphene with a paraphrased quote for the title of Harper’s posting, “It’s a bit silly for society to throw a little bit of money at (graphene) and expect it to change the world.” (Note: Within this context, mention is made of the company’s graphene opportunities report.)

With all this excitement about graphene (and carbon generally), the magazine titled Carbon has just published a suggested nomenclature for 2D carbon forms such as graphene, graphane, etc., according to an Oct. 16, 2013 news item on Nanowerk (Note: A link has been removed),

There has been an intense research interest in all two-dimensional (2D) forms of carbon since Geim and Novoselov’s discovery of graphene in 2004. But as the number of such publications rise, so does the level of inconsistency in naming the material of interest. The isolated, single-atom-thick sheet universally referred to as “graphene” may have a clear definition, but when referring to related 2D sheet-like or flake-like carbon forms, many authors have simply defined their own terms to describe their product.

This has led to confusion within the literature, where terms are multiply-defined, or incorrectly used. The Editorial Board of Carbon has therefore published the first recommended nomenclature for 2D carbon forms (“All in the graphene family – A recommended nomenclature for two-dimensional carbon materials”).

This proposed nomenclature comes in the form of an editorial, from Carbon (Volume 65, December 2013, Pages 1–6),

All in the graphene family – A recommended nomenclature for two-dimensional carbon materials

  • Alberto Bianco
    CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique, Strasbourg, France
  • Hui-Ming Cheng
    Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016, China
  • Toshiaki Enoki
    Department of Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan
  • Yury Gogotsi
    Materials Science and Engineering Department, A.J. Drexel Nanotechnology Institute, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA
  • Robert H. Hurt
    Institute for Molecular and Nanoscale Innovation, School of Engineering, Brown University, Providence, RI 02912, USA
  • Nikhil Koratkar
    Department of Mechanical, Aerospace and Nuclear Engineering, The Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA
  • Takashi Kyotani
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan
  • Marc Monthioux
    Centre d’Elaboration des Matériaux et d’Etudes Structurales (CEMES), UPR-8011 CNRS, Université de Toulouse, 29 Rue Jeanne Marvig, F-31055 Toulouse, France
  • Chong Rae Park
    Carbon Nanomaterials Design Laboratory, Global Research Laboratory, Research Institute of Advanced Materials, Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea
  • Juan M.D. Tascon
    Instituto Nacional del Carbón, INCAR-CSIC, Apartado 73, 33080 Oviedo, Spain
  • Jin Zhang
    Center for Nanochemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

This editorial is behind a paywall.