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How an iPod Could Transform Drug Testing

Researchers at Rice University  and a Houston-based startup have developed an iOS app that enables a nanoparticle-based assay to determine a drug’s toxicity to living tissue.

The mobile app essentially provides image analysis to drug screening method that is growing in popularity. The new method aims at replacing in vivo (in living subjects) methods with in vitro (in test tube) tests to determine how drugs affect living tissue.

A Houston-based startup, Nano3D Biosciences, has developed just such an in vitro test, dubbed “BiO Assay.” It creates 3-D tissue structures that mimic the results that previously could only be derived from running tests inside living tissue.

The method is based on magnetic levitation. A magnetic nanoparticle assembly consisting of gold nanoparticles, poly-L-lysine, and magnetic iron oxide binds to cells. This makes the cells themselves become magnetic so theycan be manipulated by an external magnetic field. (We’ve seen a variation on this use of magnetic nanoparticles in a cancer drug that is able to eradicate an ovarian tumor in a day.)  When the magnetic field is applied above the culture plate of the assay, the cells levitate (thus the name) from the bottom of the surface. This levitation results in them aggregating and interacting with each other to form larger 3-D cultures.

The Rice researchers took this technique and added an imaging system for it. In research published in the journal Scientific Reports (“A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis”),  the Rice team developed the iOS app as well as the analytic software, scientific protocols, and hardware to go with it. You can see an iPod equipped with the app performing its drug toxicity analysis in the video below.

The app essentially takes time-lapsed images of the 3-D cell cultures that have been exposed to varying levels of a drug. The analytical program then measures each sample and creates time-elapsed movies, graphs and charts of the drug's toxic profile.

“This literally collects about 100 000 data points during a 12-hour, overnight experiment,” said study co-author Shane Neeley, a Rice bioengineering graduate student, in a press release. “That’s all relevant publishable data that relate to the different times, doses, and cell types and other key variables in the experiment.”

Now you may be asking yourself—as I did—why is an iPod app needed for what is essentially a lab-based testing of drug toxicity? If you don’t already have the assay, this app is not going to make your iPod capable of testing the cytotoxicity of the ibuprofen you’re taking.

It turns out the interns of Nano3D Biosciences developed the app because they couldn’t be bothered with taking photos of the assay with their microscopes.

“Without looking in the microscope, just looking at the camera and clicking like a robot, it would take 20 minutes to take pictures of all 96 wells on one plate,” Glauco Souza, Nano3D’s president and chief scientific officer said in the press release. “To analyze that, all 96, with a ruler, took even longer.”

Whether this app will prove useful outside of keeping some lab interns from doing monotonous work remains to be seen. However, the team is trying to see where it can be applied next.

“We’re hoping to get this into some high school classrooms here in Houston, and we’re working with one of Houston’s largest community colleges, Lone Star College, to see if it can be used there,” Souza added.

Let's Make the Entire Chip from Graphene

The International Technology Roadmap for Semiconductors (ITRS) predicts that by 2015, copper-based vias that connect the silicon surface to a chips' wiring and connect one layer of wiring to another simply will not be able to do the job anymore. That day is a little over a year away—practically tomorrow in technological innovation terms. As a result, there is a bit of a scramble to find alternatives—not just for vias but for all sorts of interconnects used in integrated circuits (ICs).

Researchers at the University of California, Santa Barbara (UCSB) have taken an initial step in offering one possible alternative: “an integrated circuit design scheme in which transistors and interconnects are monolithically patterned seamlessly on a sheet of graphene.”

It’s been over 30 months since IBM demonstrated that it could make an integrated circuit using graphene; in this most recent research, the UCSB team demonstrated, using a computer model, that its design is feasible.  So where is the disconnect (pun intended)?

The IBM work involved a graphene field-effect transistor and inductor and other circuit components that were monolithically integrated on a single silicon wafer. The UCSB design proposes that every bit of the IC be made from graphene.

"In addition to its atomically thin and pristine surfaces, graphene has a tunable band gap, which can be adjusted by lithographic sketching of patterns—narrow graphene ribbons can be made semiconducting while wider ribbons are metallic,” explained Kaustav Banerjee, professor of electrical and computer engineering and director of the Nanoelectronics Research Lab at UCSB, in a press release. “Hence, contiguous graphene ribbons can be envisioned from the same starting material to design both active and passive devices in a seamless fashion and lower interface/contact resistances."

In the paper that was published in the journal Applied Physics Letters (“Proposal for all-graphene monolithic logic circuits”) the researchers demonstrate “that devices and interconnects can be built using the 'same starting material'—graphene.” While that is intriguing, what may really garner the interest of the semiconductor industry is the research paper's claim that, “all-graphene circuits can surpass the static performances of the 22-[nanometer] complementary metal-oxide-semiconductor devices.”

Commenting on the research, Professor Philip Kim at Columbia University noted: "This work has demonstrated a solution for the serious contact resistance problem encountered in conventional semiconductor technology. [It presents the] innovative idea of using an all-graphene device-interconnect scheme. This will significantly simplify the IC fabrication process of graphene based nanoelectronic devices."

Illustration: UCSB Nanoelectronics Research Lab

Two-Dimensional Materials Tackle the Diode

While graphene by itself has been generating enormous interest in both the research community and outside of it, what many are still missing is that we are in the midst of a two-dimensional material explosion that goes beyond just graphene.

Molybdenum disulfide (MoS2) is beginning to take center stage right behind graphene in the cast of 2-D materials that includes silicene (a single layer of silicon) and boron nitride. Nearly three years ago, MoS2 was revealed as a possible 2-D replacement for three-dimensional silicon in transistors.

Even though MoS2 had an advantage over graphene in that it has an inherent band gap, it was really first imagined as a complement to graphene in applications such as optoelectronics and energy harvesting, where thin, transparent semiconductors are required.

Now researchers at Northwestern have gone back to MoS2's complementary role and combined it with carbon nanotubes to create p-n heterojunction diode. The p-n junction forms the backbone of devices such as solar cells, light-emitting diodes, photodetectors, and lasers.

“The p-n junction diode is among the most ubiquitous components of modern electronics,” said Mark Hersam, director of the Northwestern University Materials Research Center, in a press release. “By creating this device using atomically thin materials, we not only realize the benefits of conventional diodes but also achieve the ability to electronically tune and customize the device characteristics. We anticipate that this work will enable new types of electronic functionality and could be applied to the growing number of emerging two-dimensional materials.”

In a paper published in the journal Proceedings of the National Academy of Sciences (“Gate-tunable carbon nanotube–MoS2 heterojunction p-n diode”), the Northwestern team used single-walled carbon nanotubes as the p-type semiconductor and the MoS2 as n-type semiconductor.

The researchers discovered that when they stacked the two semiconductors vertically on top of each other they formed a heterojunction that allowed for the tuning of the device’s electrical characteristics with an applied gate bias.

In addition to its tunability, the p-n heterojunction diode is highly light sensitive. The researchers exploited this capability by making an ultrafast photodetector with the diode that displayed an electronically tunable wavelength response.

With 2-D materials already proving capable of making field-effect devices, it is hoped that this latest addition of a p-n junction diode made from one will mark an important step in the next generation of electronics.

New Trick Produces Whole Wafers of Perfectly Aligned Nanowires

Nanowires don’t quite get the recognition that their high-profile nanomaterial cousins carbon nanotubes and graphene receive. But nanowires are quietly leading toward big improvements in a new generation of photovoltaicsplastic OLEDs (organic light-emitting devices), and a bunch of other applications.

Nanowires have suffered from the same manufacturing issues that other nanomaterials have endured, namely achieving large scale production while maintaining quality. One of the key problems nanowire developers have had to overcome is getting the nanowires to orient themselves in perfectly even arrays.

Researchers at the Korea Advanced Institute of Science and Technology (KAIST) in cooperation with LG Innotek have found a solution to that problem. And that solution moves away from traditional chemical synthesis to toward tricks common to semiconductor manufacturing.

In research published in the journal Nano Letters (“High Throughput Ultralong (20 cm) Nanowire Fabrication Using a Wafer-Scale Nanograting Template”), the Korean team leveraged semiconductor processes  to produce highly-ordered and arrays of long (up to 20 centimeters) nanowires, eliminating the need for post-production arrangement.

The process involves a photo engraving technique on a 20-centimeter diameter silicon wafer. First the researchers created a template on the wafer consisting of an ultrafine 100-nanometer linear grid pattern. Then they used this pattern to lay down the nanowires using a sputtering process. The method produces nanowires in bulk in perfect shapes of 50-nm width and 20 cm maximum length.

“The significance is in resolving the issues in traditional technology, such as low productivity, long manufacturing time, restrictions in material synthesis, and nanowire alignment,” commented Professor Jun-Bo Yoon of KAIST in a press release. “Nanowires have not been widely applied in the industry, but this technology will bring forward the commercialization of high performance semiconductors, optic devices, and biodevices that make use of nanowires.”

Because the process doesn’t require a long synthesis time and results in perfectly aligned nanowires, the industrial partners in the research believe that it’s a technique that should lend itself to commercialization.

Image: KAIST

Nanoparticle Helps Eradicate an Ovarian Tumor in a Day

Researchers at Florida International University (FIU) have developed a novel approach to treating ovarian cancer that employs nanoparticles in combination with a magnetic field to target cancer cells while leaving nearby healthy cells untouched.

In research published in the journal Scientific Reports (“Magneto-electric Nanoparticles to Enable Field-controlled High-Specificity Drug Delivery to Eradicate Ovarian Cancer Cells”), the FIU team demonstrated how the so-called magneto-electric nanoparticles (MENs) enable the chemotherapy drug, Taxol, to completely eradicate a tumor within 24 hours while leaving the healthy ovarian cells intact.

“Sparing healthy cells has been a major challenge in the treatment of cancer, especially with the use of Taxol; so in addition to treating the cancer, this could have a huge impact on side-effects and toxicity,” said Carolyn Runowicz, M.D., professor of gynecology and obstetrics at the Herbert Wertheim College of Medicine at FIU, in a press release.

While the use of various nanoparticles for delivering drugs to specific targets in the body has been with us for a decade now and has already created a billion-dollar industry for itself,  this marks the first time that these MENs nanoparticles have been used in this kind of therapy.

The basis of nano-enabled drug delivery has typically involved connecting the nanoparticle to some antibody that is attracted to a tumor and sending the nanoparticle through the bloodstream to find its target. There has been some question about the efficacy and specificity of this antibody approach.

This new technology developed at FIU appears to be more specific because it separates the cancer cells from the healthy cells by exploiting differences in the electrical properties of the two kinds of cells' membranes.

This separation is achieved because of the unique properties of the MENs. Unlike typical magnetic nanoparticles (MN), which can be controlled by a remote magnetic field, the MENs can have their intrinsic electric fields controlled by the external magnetic field. This means that the MENs can operate as localized magnetic-to-electric-field nano-converters. In other words, the MENs can generate the electric signals that govern molecular interactions. By creating a particular electric field, the MENs change the membrane properties of the cancer cells and not the healthy cells making them more porous.

As the Scientific Reports articles describes it: “The interaction between the MENs and the electric system of the membrane effectively serves as a field-controlled gate to let the drug-loaded nanoparticles enter specifically the tumor cells only.”

“This is an important beginning for us. I’m very excited because I believe that it can be applied to other cancers including breast cancer and lung cancer,” said Sakhrat Khizroev, professor of electrical and computer engineering at FIU in the press release.

Illustration: Florida International University

Nanostructured Ceramic Coatings Enable the Potential of Thermophotovoltaics

The concept of the thermophotovoltaic (TPV) device has been around for more than 50 years.  In that time, its promise of a theoretical conversion efficiency of over 80 percent has been a tantalizing improvement over the still meek conversion efficiencies found in the average commercially available single-junction, silicon-based solar cells that reach just 15 percent.

Despite their theoretical promise, TPV devices haven’t been able to achieve much higher than 8 percent conversion efficiency. The problem has been that the thermal emitter (one of the two main components that make up a TPV device, the other being the photovoltaic diode) has yet to be made of a material that can withstand the temperatures required to make it effective.

Now, in joint research at Stanford University, the University of Illinois at Urbana Champaign and North Carolina State University, researchers have discovered that if they coat the tungsten typically used in thermal emitters with a nanostructured layer of a ceramic material called hafnium dioxide that they developed, the emitter will withstand extreme temperatures.

The researchers, whose findings were published in the journal Nature Communications (“Three-dimensional self-assembled photonic crystals with high temperature stability for thermal emission modification”), determined that the nanostructured coating enabled thermal emitters to remain stable at temperatures as high as 1400 ºC (2500 ºF). Previous prototypes would fall apart when temperatures reached 1200 ºC. (You can see this destruction in the image [right].)

"This is a record performance in terms of thermal stability and a major advance for the field of thermophotovoltaics," said Shanhui Fan, a professor of electrical engineering at Stanford University, in a press release.

The essential difference between a TPV and your typical photovoltaic device is the thermal emitter. In  standard photovoltaics, the sun itself serves as the thermal emitter.

Unfortunately, with the sun as the thermal emitter, traditional photovoltaics can't make the most of the available energy because they are designed to take in only infrared light. All of the other, higher-energy light waves emitted from the sun are wasted as heat. The thermal emitter in a TPV device acts as an intermediary between the sun and the photovoltaic diode. It converts the higher-energy light waves into infrared light that the photovoltaic diode can convert into electricity.

"Essentially, we tailor the light to shorter wavelengths that are ideal for driving a solar cell," Fan said in the release.

While the new material the researchers developed can manage to stay stable at high temperatures, they admit that it can’t yet remain stable for the length of time that would make it viable as a component in a commercial device.

The researchers observed that when the ceramic-coated emitters were subjected to temperatures of 1000 ºC, they retained their structural integrity for more than 12 hours. At 1400 ºC, the samples began to break down after about an hour.

While 12 hours and one hour do not exactly conjure up the idea of these devices changing the photovoltaic landscape any time soon, it does open up an avenue that many had not expected was available.

"These results are unprecedented," said former Illinois graduate student Kevin Arpin, lead author of the study, in the press release. "We demonstrated for the first time that ceramics could help advance thermophotovoltaics as well other areas of research, including energy harvesting from waste heat, high-temperature catalysis, and electrochemical energy storage."

Images: Kevin Arpin

Europe Invests €1 Billion to Become "Graphene Valley"

The European Commission (EC) last week announced a €1 billion ($1.3 billion) investment in graphene research and development that will be spread over 10 years. The aim of the huge funding initiative will be to smooth the path for pushing graphene from the research lab to the marketplace.

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. One has to wonder whether it was a decision arrived at after pragmatic analysis or whether it was just a demonstration of fairness in the awarding of business meted out by the EU.

With Konstantin Novoselov—who shared the Nobel Prize for the discovery of graphene—on the Graphene Flagship board, you can’t help but ask yourself why this wasn’t all set up at the University of Manchester in the UK. (You can see Novoselov speak during the press conference for the project’s launch in the video below.) The UK government already made a $71 million investment last year to create a “Graphene Hub”.  Instead of building on an investment, it appears they just decided to make another “Graphene Hub” somewhere else in Europe.

Of course, I am somewhat dubious that these regionally focused nanotechnology investments will have the desired impact of making the next “Silicon Valley”, or “Graphene Valley” as the case may be.  We have seen what happens when a country provides financial support to the basic research, but turns away as soon as the start-ups generated from the research start to struggle: Those struggling startups get bought up by companies in other countries that don’t support the basic research. The fruits of all that national investment are enjoyed by other countries.

This latest funding will likely result in some new research facilities being built.  To that extent, we know that this will generate some employment. However, I hope over the 10-year span of the initiative, it will become clear that actually supporting the development of graphene applications does not just involve the supporting of the local construction industry, but also includes funding the small businesses out there trying to bring this technology to market.

Photo: Chalmers

Computer Model Shows Carbyne is the Strongest Known Material

Researchers at Rice University have developed computer models that reveal that the long-theorized material carbyne is the strongest material in the world.

The research, which was published in the journal ACS Nano (“Carbyne from First Principles: Chain of C Atoms, a Nanorod or a Nanorope”), demonstrated that carbyne should have the greatest tensile strength of any other known material, double that of graphene which itself is 200 times stronger than steel.

Boris Yakobson, a theoretical physicist at Rice who led the research, has previously demonstrated through computer modeling important possibilities for the use of carbon materials, like graphene. In the case of this carbyne research, as with his research into graphene, it remains to be seen whether the computer models can be duplicated in the physical world.

As the press release covering the research describes it: “Carbyne is a chain of carbon atoms held together by either double or alternating single and triple atomic bonds.” It has been encountered in highly compressed graphite. While there have been some demonstrations of the material being synthesized at room temperature,  it’s not clear how it could be produced in bulk.

If such a method could be developed, the Rice researchers believe that the material could be useful in a range of applications.

“You could look at it as an ultimately thin graphene ribbon, reduced to just one atom, or an ultimately thin nanotube,” said Yakobson in the press release. “It could be useful for nanomechanical systems, in spintronic devices, as sensors, as strong and light materials for mechanical applications or for energy storage.”

While the mere fact that carbyne is the strongest possible assembly of atoms is exciting to the Rice researchers, it will take a bit more research to exploit that strength. It wasn’t until recently that the strength of graphene could be fully exploited in a composite material.

The next step for the researchers will be to investigate the possibility of one-dimensional chains of atoms for other elements.

Image: Vasilii Artyukhov/Rice University

There Is No Nanotechnology Equivalent to the Digital Divide

A recent article in the venerable Financial Times proposed a sort of nanotechnology equivalent to the oft-mentioned “digital divide (the idea that the benefits of digital technology appear to accrue to the wealthy while the poor are left out). At issue in the article is whether developed economies and poorer nations are separated in their respective access to nanotechnology.

So, is there a nanotech divide?

The answer probably lies somewhere between “yes” and “no,” depending on the metric you use. But I would argue that nanotechnology has been one of the most egalitarian fields in technology history.

First, you can look at where the money goes. On this count, nanotechnology is basically the same as any other emerging technology: the initial targeted applications are those that can sustain the price premium for using a new and expensive technology.

However, nanomaterials can already be found in inexpensive items ranging from odor-resistant socks to plastic beer bottles.  So as the manufacturing technologies have matured and ramped up, we have seen prices fall and the democratization of nano-enabled products spread.

But I've often argued that analyzing nanotech's impact purely on economic terms can be misleading. It is usually a stretch to try to draw parallels between an emerging technology like nanotech and a developed field like information technology. Nanotech is still in its commercial infancy.

Instead, let's focus just on nanotechnology research, which constitutes the bulk of the activity in the field today. With nanotech, we are probably witnessing the most democratic and open-access research ever in a new technology.

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Silicon and Graphene: Two Great Materials That Stay Great Together

The use of graphene as a transparent conducting film has been hotly pursued of late, in large part because it offers a potentially cheaper alternative to indium tin oxide (ITO) where a bottleneck of supply seems to be looming.

It has not been clear whether photovoltaic manufacturers have taken any interest in graphene as an alternative for transparent conducting films. This lack of interest may in part be the result of there being little research into whether graphene maintains its attractive characteristic of high carrier mobility when used in conjunction with silicon.

Now researchers at the Helmholtz Zentrum Berlin (HZB) Institute in Germany have shown that graphene does not lose its impressive conductivity characteristics even when mated with silicon.

"We examined how graphene's conductive properties change if it is incorporated into a stack of layers similar to a silicon based thin film solar cell and were surprised to find that these properties actually change very little," said Marc Gluba of the HZB Institute for Silicon Photovoltaics in a press release.

The research, which was published in the journal Applied Physics Letters (“Embedded graphene for large-area silicon-based devices”), used the method of growing the graphene by chemical vapor deposition on a copper sheet and then transferring it to a glass substrate. This was then covered with a thin film of silicon.

The researchers experimented with two different forms of silicon commonly used in thin-film technologies: amorphous silicon and polycrystalline silicon. In both cases, despite completely different morphology of the silicon, the graphene was still detectable.

"That's something we didn't expect to find, but our results demonstrate that graphene remains graphene even if it is coated with silicon," said Norbert Nickel, another researcher on the project, in a press release.

In their measurements, the researchers determined that the carrier mobility of the graphene layer was roughly 30 times greater than that of conventional zinc oxide-based contact layers.

Although the researchers concede that connecting the graphene-based contact layer to external contacts is difficult, it has garnered the interest of their thin-film technology colleagues. "Our thin film technology colleagues are already pricking up their ears and wanting to incorporate it,” Nickel adds.

Illustration: Marc A. Gluba/HZB



IEEE Spectrum’s nanotechnology blog, featuring news and analysis about the development, applications, and future of science and technology at the nanoscale.

Dexter Johnson
Madrid, Spain
Rachel Courtland
New York City
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