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Drug Delivery Research Gets a New Nanotech Tool in its Arsenal

 

Earlier this year, IBM Zurich demonstrated, for the first time, the ability to image the charge distribution of a molecule. Now researchers at the University of Zurich, led by Prof. Madhavi Krishnan, have developed a method that makes possible the measurement of the electrostatic charge of nanoparticles for the first time. 

The research, which was published in the journal Nature Nanotechnology ("Measuring the size and charge of single nanoscale objects in solution using an electrostatic fluidic trap") developed a method by which “single nanoscale objects can be directly measured with high throughput by analyzing their thermal motion in an array of electrostatic traps.”

Krishnan and her colleagues set up the “electrostatic traps” by using glass plates the size of computer chips and creating energy holes between the two plates of glass. Each hole contains a weak electrostatic charge, so when a solution is dropped on the glass plates, particles get trapped there. Because molecules from the solution continue to bounce off the trapped particles, the particles are forced into a circular motion within the traps. It is this motion that enables the measurement of the charge of each particle.

Those of you familiar with the work of the 1923 Nobel Prize winner in physics—Robert A. Millikan—might be thinking that this sounds remarkably similar to the traps he created to measure the velocity of oil drops. “But he examined the drops in a vacuum,” Prof. Krishnan explains in a press release. “We on the other hand are examining nano particles in a solution which itself influences the properties of the particles.”

The ability to measure charge in solution is critical. It is in fact the electrical charge of the particles within the solution that determines the consistency of various solutions ranging from blood to pharmaceuticals. “With our new method, we get a picture of the entire suspension along with all of the particles contained in it,” Krishnan says. “The charge of the particles plays a major role in this.”

The scientists believe that the ability to make these measurements of a single nanoparticle in real time will alter the way research is conducted for nanoparticles used in drug delivery. Any change in charge to a nanoparticle due to its reactions to various proteins and other large molecules can dramatically affect how the nanoparticle interacts in the body when carrying out a function like delivering a drug.

DNA Scaffold Delivers Payload of Synthetic Vaccines Safely and Effectively

About 18 months ago, the nanotech trade press was buzzing with the work of Hongbin Yu and Hao Yan, both from Arizona State University (ASU), when they developed a method that used DNA origami as a scaffold. When the DNA scaffolding was combined with “nano islands” made from gold, it enabled the manufacturing of smaller electronic memory devices. 

Now Yan has joined with Yung Chang, a biodesign immunologist also from ASU, to use three-dimensional DNA structures as a scaffold on which they piggybacked synthetic vaccine complexes to make the delivery of the vaccines safer and more effective. 

“When Hao treated DNA not as a genetic material, but as a scaffolding material, that made me think of possible applications in immunology,” said Chang, an associate professor in the School of Life Sciences and a researcher in the Biodesign Institute’s Center for Infectious Diseases and Vaccinology in a university press release. “This provided a great opportunity to try to use these DNA scaffolds to make a synthetic vaccine.”

The research, which was published in the journal Nano Letters ("A DNA Nanostructure Platform for Directed Assembly of Synthetic Vaccines"),  made its first test with the DNA scaffold by placing an immune stimulating protein called streptavidin (STV) and an immune response boosting compound called an adjuvant (CpG oligo-deoxynucletides) to different branches of the DNA structure.

After determining that cells would absorb the DNA structure with its synthetic vaccine payload, the researchers waited to see if an immune cascade response would follow. It did and was really beyond the researchers expectations.

The results showed that the mice that were given the full vaccine complex consisting of the DNA scaffold and the STV and GpG displayed an immune response nine times higher than those that had been injected solely with the STV and GpG.

"We were very pleased," said Chang in the press release. "It was so nice to see the results as we predicted. Many times in biology we don't see that."

This is really just a leaping off point, according to the researchers. They believe that this proof of concept indicates that an unlimited range of antigens could be used in this way for fighting a host of diseases.

Nanosensor Could Detect Prostate Cancer in its Early Stages

Sensors for detecting chemical biomarkers that indicate a disease have already been applied to some maladies, but they have not proven very effective at discovering low concentrations of those biomarkers, such as when a disease is in its early stages. This is a problem, because often the key to successful treatment is early detection. 

Now researchers at the London Centre for Nanotechnology at Imperial College London and the University of Vigo have developed plasmonic nanosensors that could enable early disease detection by picking up biomarker signals at very low concentrations

The research, which was published in the journal Nature Materials (“Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth”), demonstrated a signal-generation mechanism for nanoparticle sensors capable of creating “a signal that is larger when the target molecule is less concentrated.” Earlier this year we saw researchers at Brown University experiment with plasmonics for biosensors to measure glucose levels via saliva rather than blood.  

In the initial testing with the new London nanoparticle sensor the researchers looked for the biomarker associated with prostate cancer, called prostate specific antigen (PSA). The nanosensor was capable of detecting PSA in concentrations nine orders of magnitude smaller than today's enzyme-linked immunosorbent assay (ELISA) tests.

The LCN nanosensors are made up of gold nanoparticles that are floating in proteins derived from blood serum. On the surface of the gold nanoparticles are differnet antibodies. One antibody latches onto the PSA when it detects it while the other antibody creates a silver crystal coating that floats on the surface of the nanoparticle when it comes in the presence of the PSA. The silver crystal coating is detected by optical microscopes. The improved “signal-generation mechanism” is that this silver crystal coating is more apparent when the concentration of the PSA is low.

Professor Molly Stevens, senior author of the study from the Departments of Materials and Bioengineering at Imperial College London, notes in a press release: “It is vital to detect diseases at an early stage if we want people to have the best possible outcomes – diseases are usually easier to treat at this stage, and early diagnosis can give us the chance to halt a disease before symptoms worsen. However, for many diseases, using current technology to look for early signs of disease can be like finding the proverbial needle in a haystack. Our new test can actually find that needle. We only looked at the biomarker for one disease in this study, but we’re confident that the test can be adapted to identify many other diseases at an early stage.”

The First Printable Giant Magnetoresistive Devices Emerge

Last month, researchers at the University of Utah developed a “plastic paint” magnetic field sensor based on spintronics that looks as though it could ultimately find its way into consumer electronics. 

Along these lines, researchers in Germany are now reporting they have developed the first printable magnetic sensor that relies on giant magnetoresistance (GMR) effect. The research, initially published in the online edition of Advanced Materials ("Printable Giant Magnetoresistive Devices"), was performed by a team at IFW Dresden.

The researchers claim that the magneto-sensitive ink can be painted on just about any substrate and maintains a GMR ratio of up to 8 percent at ambient conditions. With a typical spin valve GMR ratio reaching just 5 percent for read heads inside your computer, this GMR ratio alone is pretty impressive. However, it is what the work augurs for the field of printable electronics that may have the most lasting impact.

"Our demonstrator with a magnetic switch printed on a postcard suggests that the vision of interactive fully printable electronics can become reality," Dr. Denys Makarov, leader of the group "Magnetic Nanomembranes" at the IFW Dresden, tells Nanowerk in the story covering the research.

The demonstrator Makarov refers to involved integrating the printable GMR sensor into a hybrid electronic circuit. The circuit consisted of an amplifier with a light emitting diode (LED) that had been printed on a postcard. A permanent magnet modifies the resistance of the printable magnetic sensor to switch the LED between its on/off states.

While it appears that the GMR ink can be applied by a variety of methods, such as roll-to-roll or flexography, each method demands different sized GMR flakes in the ink as well as different ink viscosity.

Makarov further notes in the Nanowerk story: “More investigations are required to understand the influence of the size of GMR flakes on the resulting GMR response of the magneto-sensitive ink. Furthermore, different binder solutions have to be tested to adjust the viscosity and conductivity of the ink."

New Method Developed for Making a Transistor from Graphene

 

Researchers from Germany and Sweden have developed a new method for creating a transistor from graphene, according to an artlcle at Phys.org.

The headline, "Researchers devise a way to create a graphene transistor," is a bit misleading. Researchers have been making transistors out of graphene for some time now,  and have been using a process based on silicon carbide, like the German-Swedish research. 

The real breakthrough for this latest line of research, which was published 17 July in the journal Nature Communications (“Tailoring the graphene/silicon carbide interface for monolithic wafer-scale electronics”),  appears to be how they engineered all the constituent parts of the transistor.

To be honest, I am not entirely clear on how even their process diverges drastically from the IBM research. After a year of trying to figure out how to connect all the parts of the graphene-based transistor without damaging it, the IBM team used electron beam lithography and a resist that was sensitive to electrons.The German-Swedish researchers used electron beam lithography too.

Maybe the difference between the two is the use of oxygen plasma etching, which converted the middle channel on the transistor from a contact into a gate. This could be the “tailoring the graphene/silicon carbide interface” of which the paper title speaks.

An important caveat to the research is that because the researchers had to scale up dramatically their transistor they don’t really know how much faster the transistor might be than the current variety. Furthermore, they’re not even sure how fast it might be when they scale the transistor down.

I am sure this work is helpful and evolutionary research in the development of graphene transistors, but I think maybe the Phys.org article has perhaps overstated its case when it says that this research “is the breakthrough computer engineers have been waiting for.”

Nanoparticle Completely Eradicates Hepatitis C Virus

 

Researchers at the University of Florida (UF) have developed a nanoparticle that has shown 100 percent effectiveness in eradicating the hepatitis C virus in laboratory testing. 

The nanoparticle, dubbed a nanozyme, consists of a backbone made from gold nanoparticles and a surface with two biological components. One biological component is an enzyme that attacks and destroys the mRNA, which provides the recipe for duplicating the protein that causes the disease. The other biological part is the navigator, if you will. It is a DNA oligonucleotide that identifies the disease-related protein and sends the enzyme on course to destroy it.

Y. Charles Cao, a UF associate professor of chemistry, and Dr. Chen Liu, a professor of pathology at the UF College of Medicine published their research online this week in the Proceedings of the National Academy of Sciences ("Nanoparticle-based artificial RNA silencing machinery for antiviral therapy"). 

The basis of the work is mimicking the biological process of RNA interference, which researchers in the past have used effectively in the laboratory for treating HIV. In the UF research the nanoparticle mimics the function of RNA-induced silencing complex (RISC), which mediates the RNA interference process.

Current hepatitis C treatments do attack the replication process of the virus but they are not entirely effective and only help about 50 percent of the patients treated with them. Cao and Liu along with their team wanted to see if they could improve upon that percentage. The researchers claim that their treatment (in cell culture and mice) led to a near 100 percent eradication of the hepatitis C virus without bringing on any side effects caused by the immune system attacking the treatment.

Of course, this is a long way from becoming a treatment anytime soon. A major caveat is that the use of nanotreatments for the targeting and destroying of abnormal cells like cancer cells is always problematic since those cells are “still us” as George Whitesides noted some time back.  It’s always a bit of a tricky business to make sure that nanoparticles are targeting those biological processes within us that we want stopped and not the ones we want to keep.

Further complicating this particular line of research is some of the terminology that is part of the press release. They have decided to use the term “nanorobots” to describe the nanoparticles, apparently because that can really excite the general public about what might otherwise be a fairly niche story.  That’s fine, I suppose. Whatever manages to get the public interested in what is genuinely ground breaking research. The problem is that it creates confusion in some terribly misguided people who are convinced that we are about to be overrun by ‘nanobots’ that will render the planet into nothing but “gray goo”.   Can’t we just retire the term “nano robots” for the sake of human life?

Nanomaterial Duplicates Self-Regulation of Living Organisms

Bio-inspired nanomaterials seem to be the rage this week, at least on this blog.  Adding to the furor, researchers at Harvard University have developed a nanomaterial that can actively self-regulate depending on environmental changes. 

While living organisms have developed sophisticated systems for responding to the external environment, the Harvard team believe this to be the first instance in which artificial materials have been able to self-regulate themselves in response to external factors, such as temperature or pH.

The research, which was published in the July 12th issue of Nature, aimed initially at making the material regulate itself based on temperature. But the researchers believe in principle that the material can be made to regulate itself according to pH, pressure or some other parameter. This ability to self-regulate itself according to a variety of external factors is one of the features that distinguish it from something like photochromic eyeglasses, which can only react to a single stimulus and cannot self-regulate.

The material itself is fairly simple. Dubbed SMARTS (Self-regulated Mechano-chemical Adaptively Reconfigurable Tunable System), it consists of nanofibers that have been embedded into a hydrogel. When set up for temperature regulation, the hydrogel swells in the presence of colder temperatures causing the nanofibers to stand upright; and it contracts in warmer temperatures causing the nanofibers to lie down.

“Think about how goosebumps form on your skin,” explains lead author Joanna Aizenberg, and Professor of Materials Science at the Harvard School of Engineering and Applied Sciences (SEAS) in the university press release covering the research. “When it is cold out, tiny muscles at the base of each hair on your arm cause the hairs to stand up in an insulating layer. As your skin warms up, the muscles contract and the hairs lie back down to keep you from overheating. SMARTS works in a similar way.”

This is clearly early stage research, but the researchers have suggested applications in medical implants and buildings that could react to the outside temperatures. Added to these fairly specific applications are the broad fields of robotics, computing and healthcare.

“Whether it is the pH level, temperature, wetness, pressure, or something else, SMARTS can be designed to directly sense and modulate the desired stimulus using no external power or complex machinery, giving us a conceptually new robust platform that is customizable, reversible, and remarkably precise,” co-lead author Ximin He noted.

Tightening Graphene Like a Drumhead Changes Its Electrical Properties

 

The main preoccupation with graphene research has been trying to impart a band gap to the wonder material. Researchers at the University of Wisconsin-Milwaukee were able to get graphene to behave like a semiconductor earlier this year by making a new variety of graphene dubbed “graphene monoxide”. But now researchers at National Institute of Standards and Technology (NIST) and the University of Maryland discovered they could do it by just treating graphene like a drumhead

The research was published in the journal Science under the title “Electromechanical Properties of Graphene Drumheads”  and is available with a subscription.

Initially the aim of the NIST and University of Maryland team was to see if they could just slow electrons down with the use of a substrate. So they suspended a layer of graphene over a substrate of silicon dioxide that contained shallow holes. When the graphene was laid on top of these holes, it formed a kind of graphene drumhead.

The next step, of course, was to measure their new graphene drumhead. It was then that they discovered when the tip of the scanning probe microscope (SPM) approached the graphene, it rose up to meet the tip. The attraction of the graphene to the SPM tip was caused by van der Waal force, in which a weak electrical force is created that attracts objects together. 

"While our instrument was telling us that the graphene was shaped like a bubble clamped at the edges, the simulations run by our colleagues at the University of Maryland showed that we were only detecting the graphene's highest point," says NIST scientist Nikolai Zhitenev in the NIST press release covering the research. "Their calculations showed that the shape was actually more like the shape you would get if you poked into the surface of an inflated balloon, like a teepee or circus tent."

The researchers then tinkered with the graphene drumhead a little more and soon discovered that they could tighten the graphene like one would with the skin on a real drum. But instead of changing the sound as with the real drum, the tightening of the graphene drumhead resulted in changing the electrical properties of the graphene.

If you tightened the graphene drumhead enough so that it actually went into the shallow hole and created a kind of tent like shape, the graphene started to behave like a quantum dot.

This result could open up an entirely new avenue of research in which by simply altering the shape of graphene you can maintain its high conductivity but create a band gap as well.

Zhitenev further noted in the release: "Normally, to make a graphene quantum dot, you would have to cut out a nanosize piece of graphene," says NIST fellow Joseph Stroscio. "Our work shows that you can achieve the same thing with strain-induced pseudomagnetic fields. It's a great result, and a significant step toward developing future graphene-based devices."

Nanostructures Modeled on the Moth Eye Reduce Radiation in Medical Imaging

Typically it’s the butterfly that serves as the bio-inspiration for nanotechnology advances.  But now the butterfly’s modest cousin, the moth, is serving as the model.

Yasha Yi, a physics professor at the City University of New York, has attempted to duplicate the moth’s anti-reflective eyes with a nanostructured material that should improve medical imaging

This is not the first time that the anti-reflective qualities of moth eyes have been used as models for devices. Researchers have attempted to duplicate this feature to create more efficient coatings for solar panels and some military devices. But Yi and his research team, which published their work in the journal Optics Letters,  were looking at improving “scintillation” materials used in medical imaging technologies. These scintillation materials absorb incoming X-rays and reemit the energy as light of wavelengths that can be picked up by a detector.

If you want the detector to pick up more light, the technique has usually been to increase the intensity of the X-rays. But this obviously has associated health risks. Yi and his team believed that if they could improve the scintillation material so that it reemitted more light from the same amount of X-rays, then they could create safer medical imaging devices.

To do this, the researchers needed to create a new class of materials. What they came up with is based on a thin film made from cerium-doped lutetium oxyorthosilicate crystals. They were then able to cover these crystals with pyramid-shaped bumps made of silicon nitride. It is these bumps that make the scintillator appear like the moth’s eye and give the structures its ability to extract more light.

The results have been pretty dramatic. Yi and his team measure that adding their moth-eye-inspired thin film to the scintillator of an X-ray mammographic unit increases the amount of reemitted light by 175 percent.

“The moth eye has been considered one of the most exciting bio structures because of its unique nano-optical properties,” Yi says in Nanomagazine article. “Our work further improved upon this fascinating structure and demonstrated its use in medical imaging materials, where it promises to achieve lower patient radiation doses, higher-resolution imaging of human organs, and even smaller-scale medical imaging. And because the film is on the scintillator,” he adds, “the patient would not be aware of it at all.”

We shouldn’t expect to see this scintillator material on the market in the near future. Yi expects that it will be another three to five years to evaluate and perfect the film.

Nanoscale Vacuums Speed Semiconductors

When you want to make the point of how far electronics and computer technology have come in the last sixty years, you likely refer to the old computers that used vacuum tubes for circuitry.

So, it’s a bit counterintuitive to see the latest research that suggests vacuums may be the way forward to help semiconductor electronics keep pace with Moore’s law. Researchers at the University of Pittsburgh have developed a method for generating a vacuum within a semiconductor device to transport electrons more efficiently through it. 

“Physical barriers are blocking scientists from achieving more efficient electronics,” said Hong Koo Kim, principal investigator on the project and Bell of Pennsylvania/Bell Atlantic Professor in the University of Pittsburgh’s Swanson School of Engineering, in a press release. “We worked toward solving that road block by investigating transistors and its predecessor—the vacuum.”

Of course, there already exist vacuum electronic devices, but these require high voltage. The researchers, who published their findings in the journal Nature Nanotechnology, designed an entirely new vacuum electronic device that requires minimal voltage to operate.

The key to the design was the discovery by Kim's team that it was fairly easy to pull electrons out into the air when they are trapped at the interface of an oxide or metal layer inside a semiconductor. These trapped electrons form a two-dimensional electron gas.

The researchers exploited the phenomenon known as Coulombic Repulsion--the repulsive force between two positive or negative charges--to emit the electrons from this electron gas layer. By then applying a small voltage of  1V to the silicon structure, the electrons were extracted into the air, which made it possible for them to travel ballistically in a nanometer-scale vacuum channel without the scattering typically seen in conventional devices.

Kim further noted in the release, “The emission of this electron system into vacuum channels could enable a new class of low-power, high-speed transistors, and it’s also compatible with current silicon electronics, complementing those electronics by adding new functions that are faster and more energy efficient due to the low voltage."

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Nanoclast

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

 
Editor
Dexter Johnson
Madrid, Spain
 
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Rachel Courtland
Associate Editor, IEEE Spectrum
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