MATERIALS ENGINEERING

Small is promising when it comes to illuminating tiny tumors or precisely delivering drugs, but many worry about the safety of nano-scale materials. Now a team of scientists has created minuscule flakes of silicon that glow brightly, last long enough to slowly release cancer drugs, then break down into harmless by-products.

"It is the first luminescent nanoparticle that was purposely designed to minimize toxic side effects," said Michael Sailor, a chemistry professor at the University of California, San Diego who led the study.

Many nanoparticles tested in research labs are too poisonous for use in humans.

"This new design meets a growing need for non-toxic alternatives that have a chance to make it into the clinic to treat human patients," Sailor said.

The particles inherently glow, a useful property that is most commonly achieved by including toxic organic chemicals or tiny structures called quantum dots, which can leave potentially harmful heavy metals in their wake.

When the researchers tested their safer nanoparticles in mice, they saw tumors glow for several hours, then dim as the particles broke down. Levels dropped noticeably in a week and were undetectable after four weeks, they report in Nature Materials February 22.

This is the first sudy to image tumors and organs using biodegradable silicon nanoparticles in live animals, the authors say.

The particles begin as thin wafers made porous with an electrical current then smashed to bits with ultrasound. Additional treatment alters the physical structure of the flakes to make them glow red when illuminated with ultraviolet light.

Luminescent particles can reveal tumors too tiny to detect by other means or allow a surgeon to be sure all of a cancerous growth has been removed.

These nanoparticles could also help deliver drugs safely, the researchers report. The cancer drug doxorubicin will stick to the pores and slowly escape as the silicon dissolves.

"The goal is to use the nanoparticles to chaperone the drug directly to the tumor, to release it into the tumor rather than other parts of the body," Sailor said.

Targeted delivery would allow doctors to use smaller doses of the drug. At doses high enough to be effective, when delivered to the whole body, doxorubicin often has toxic side effects.

At about 100 nanometers, these particles are bigger than many designed to deliver drugs, which can be just a few nanometers across – a thousand times smaller than the diameter of a human hair.

Their larger size contributes to both their effectiveness and their safety. Large particles can hold more of a drug. Yet they self-destruct, and the remnants can be filtered away by the kidneys.

Close examination of vulnerable organs like liver, spleen and kidney, which help to remove toxins, revealed no lasting changes in mice treated with the new nanoparticles.

Graduate students Ji-Ho Park and Luo Gu in Sailor's lab; Sangeeta Bhatia, bioengineering professor at the Massachusetts Institute of Technology and graduate student Geoffrey von Malzahn in Bhatia's lab; and Erkki Ruoslahti, professor at the University of California, Santa Barbara all contributed to this work.

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Journal reference:

1. Park et al. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nature Materials, 2009; DOI: 10.1038/nmat2398

MARCH 1,2009
An innovative and easily implemented technique in which nanoscale elements precisely assemble themselves over large surfaces could soon open doors to dramatic improvements in the data storage capacity of electronic media, according to scientists at the University of California, Berkeley, and the University of Massachusetts Amherst (UMass Amherst).

"I expect that the new method we developed will transform the microelectronic and storage industries, and open up vistas for entirely new applications," said co-lead investigator Thomas Russell, director of the Materials Research Science and Engineering Center at UMass Amherst, visiting Miller Professor at UC Berkeley's Department of Chemistry, and one of the world's leading experts on the behavior of polymers. "This work could possibly be translated into the production of more energy-efficient photovoltaic cells, for instance."

Russell conceived of this new approach with co-lead investigator Ting Xu, a UC Berkeley assistant professor with joint appointments in the Department of Material Sciences and Engineering and the Department of Chemistry. They describe their work in the Feb. 20 issue of the journal Science.

"The density achievable with the technology we've developed could potentially enable the contents of 250 DVDs to fit onto a surface the size of a quarter," said Xu, who is also a faculty scientist at Lawrence Berkeley National Laboratory.

Xu explained that the molecules in the thin film of block copolymers - two or more chemically dissimilar polymer chains linked together - will self-assemble into an extremely precise, equidistant pattern when spread out on a surface, much like a regiment of disciplined soldiers lining up in formation. For more than a decade, researchers have been trying to exploit this characteristic for use in semiconductor manufacturing, but they have been constrained because the order starts to break down as the size of the area increases.

Once the formation breaks down, the individual domains cannot be read or written to, rendering them useless as a form of data storage.

To overcome this size constraint, Russell and Xu conceived of the elegantly simple solution of layering the film of block copolymers onto the surface of a commercially available sapphire crystal. When the crystal is cut at an angle - a common procedure known as a miscut - and heated to 1,300 to 1,500 degrees Centigrade (2,372 to 2,732 degrees Fahrenheit) for 24 hours, its surface reorganizes into a highly ordered pattern of sawtooth ridges that can then be used to guide the self-assembly of the block polymers.

With this technique, the researchers were able to achieve defect-free arrays of nanoscopic elements with feature sizes as small as 3 nanometers, translating into densities of 10 terabits per square inch. One terabit is equal to 1 trillion bits, or 125 gigabytes.

Because crystals come in a variety of sizes, there are few limitations to how large this block copolymer array can be produced, the researchers said. They also noted that the angle and depth of the sawtooth ridges can be easily varied by changing the temperature at which the crystal is heated to fine tune the desired pattern.

"We can generate nearly perfect arrays over macroscopic surfaces where the density is over 15 times higher than anything achieved before," said Russell. "With that order of density, one could get a high-definition picture on a screen the size of a JumboTron."

"It's one thing to get dozens of soldiers to stand in perfect formation in an area the size of a classroom, each person equidistant from the other, but quite another to get tens of trillions of individuals to do so on the field in a football stadium," Xu added. "Using this crystal surface as a guide is like giving the soldiers a marker so they know where to stand."

Other research teams across the country are engaged in similar efforts to break the size barrier of self-assembled block copolymers, but this new project by the UMass Amherst-UC Berkeley scientists differs in that it does not rely upon advances in lithography to achieve its goals.

In the semiconductor industry, optical lithography is a process in which light passes through a mask with a desired circuit pattern onto a photosensitive material, or photoresist, that undergoes a chemical change. Several steps of chemical treatment are then used to develop the desired pattern for subsequent use.

To keep up with Moore's Law and the demand for increasingly smaller features for semiconductors and microprocessors, industry has turned to nanolithography and the use of ever-shorter wavelengths of light at greater cost.

"The challenge with photolithography is that it is rapidly approaching the resolution limits of light," said Xu. "In our approach, we shifted away from this 'top down' method of producing smaller features and instead utilized advantages of a 'bottom up' approach. The beauty of the method we developed is that it takes from processes already in use in industry, so it will be very easy to incorporate into the production line with little cost."

An added benefit, said Xu, is that "our technique is more environmentally friendly than photolithography, which requires the use of harsh chemicals and acids."

UC Berkeley and UMass Amherst have filed a joint patent on this technology.

The U.S. Department of Energy and the National Science Foundation helped support this research.

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Journal reference:

1. Park et al. Macroscopic 10-Terabit-per-Square-Inch Arrays from Block Copolymers with Lateral Order. Science, 2009; 323 (5917): 1030 DOI: 10.1126/science.1168108

FEB 27,2009
Researchers at Purdue University have developed a technique using spun-sugar filaments to create a scaffold of tiny synthetic tubes that might serve as conduits to regenerate nerves severed in accidents or blood vessels damaged by disease.

The sugar filaments are coated with a corn-based degradable polymer, and then the sugar is dissolved in water, leaving behind bundles of hollow polymer tubes that mimic those found in nerves, said Riyi Shi, an associate professor in Purdue's Weldon School of Biomedical Engineering and Department of Basic Medical Sciences.

The scaffold could be used to promote nerve regeneration by acting as a bridge placed between the ends of severed nerves, said biomedical engineering doctoral student Jianming Li, who is a member of Shi's research team that developed the technique.

The researchers are initially concentrating on the peripheral nerves found in the limbs and throughout the body because nerve regeneration is more complex in the spinal cord. About 800,000 peripheral nerve injuries are reported annually in the United States, with about 50,000 requiring surgery.

The approach also might have applications in repairing blood vessels damaged by trauma and disease such as atherosclerosis and diabetes, Shi said.

The new approach represents a potential alternative to the conventional surgical treatment, which uses a nerve "autograft" taken from the leg or other part of the body to repair the injured nerves. Researchers are trying to develop artificial scaffolds to replace the autografts because removing the donor nerve causes a lack of sensation in the portion of the body where it was removed.

"The autograft is the lesser of two evils because you have to sacrifice a healthy nerve to repair a damaged segment," said Li, who led the research.

New findings were published online in December and this month in the print edition of the journal Langmuir. The paper was written by Li, biomedical engineering doctoral student Todd A. Rickett and Shi. Rickett also is attending the Indiana University School of Medicine in an MD-Ph.D. program.

Researchers from Cornell University published similar findings online Feb. 9 in the journal Soft Matter. Those findings focused on using the technique to create vascular networks for providing blood and nutrients to tissues and grafts.

The synthetic scaffold resembles the structural assembly of natural nerves, which are made of thousands of small tubes bundled together. These tubes act as sheaths that house the conducting elements of the nerve cell.

The first step in making the tubes is to spin sugar fibers from melted sucrose.

"It's basically like making cotton candy," Li said.

The sugar filaments were coated with a polymer called poly L-lactic acid. After the filaments were dissolved, hollow tubes of the polymer remained. The researchers then grew nerve-insulating cells called Schwann cells on these polymer tubes. These cells automatically aligned lengthwise along the tubes, as did nerve cells grown on top of the Schwann cells.

This alignment is critical for the fast growth of nerves, Shi said.

Nerve cells grew not only inside the hollow tubes but also around the outside of the tubes.

"This finding is important because the increased surface area may accelerate the regeneration process following an accident," Li said.

The scaffolds are designed specifically to regenerate a portion of a nerve cell called the axon, a long fiber attached to the cell body that transmits signals. Fast regeneration is essential to prevent the atrophy of muscles and organs connected to severed nerves.

The researchers also discovered that the polymer tubes contain pores that are ideal for supplying nutrients to growing nerve cells and removing waste products from the cells.

Images of the polymer-coated sugar strands were taken using a scanning electron microscope. Another instrument, called an atomic force microscope, was used to obtain images of the hollow tubes and pores in the walls of the tubules. Other images using fluorescent dyes revealed the nerve cell alignment along the tubes.

The work was done using cell cultures in petri dishes, but ongoing work focuses on implanting the scaffolds in animals.

The method for creating the scaffolds is relatively simple and inexpensive and does not require elaborate laboratory equipment, Shi said.

"This is low-tech," he said. "We used the same kind of sugar found in candy and a cheap polymer to make samples of these scaffolds for a few dollars. The process easily lends itself to mass production. It is a unique idea, and the simplicity and efficiency of this technology distinguish it from other approaches for nerve repair."

A provisional patent application on the material has been filed.

This study was conducted at Purdue's Center for Paralysis Research, which receives funding support from the state of Indiana. Shi's lab is supported by both the National Institutes of Health and the National Science Foundation. Li was supported by the NSF's Graduate Teaching Fellows in K-12 Education Program, which strives to help graduate students bring their research and practice into the K-12 classrooms and inspire students to pursue careers in science and engineering. Li used knowledge gained in the laboratory to teach middle school students and worked on curriculum development. Rickett is supported through the Indiana Clinical and Translational Sciences Institute, which funds research on developing new technologies into effective medical therapies.

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Just as sonar sends out sound waves to explore the hidden depths of the ocean, electrons can be used by scanning tunnelling microscopes to investigate the well-hidden properties of the atomic lattice of metals.

As researchers from Göttingen, Halle and Jülich now report in the journal Science, they succeeded in making bulk Fermi surfaces visible in this manner. Fermi surfaces determine the most important properties of metals.

"Fermi surfaces give metals their personality, so to speak," explained Prof. Stefan Blügel, Director at the Jülich Institute of Solid State Research. Important properties, such as conductivity, heat capacity and magnetism, are determined by them. On the Fermi surfaces inside the atomic union, high-energy electrons are in motion. Depending on what form the surfaces have and what mobility is assigned to the electrons, they determine the physical properties of metals.

In their latest publication, the researchers report on how they used a scanning tunnelling microscope to direct electrons into a copper sample. As electrons spread out like waves, they pass through the metal and are scattered and reflected at obstacles in the bulk, such as single cobalt atoms. "The overlap between incoming and outgoing waves is so strong," said Dr. Samir Lounis from Forschungszentrum Jülich who turned the theoretical calculations into an experiment, "that they can be measured as spherical patterns on the surface using the scanning tunnelling microscope."

The somewhat deformed rings on the surface allow us to draw direct conclusions on the shape of the Fermi surfaces and the depth of the cobalt atoms, similar to how sonar recognises the ocean floor by means of reflected sound waves. "We hope that more sophisticated methods will make it possible to gain a detailed understanding of deep impurities and interfaces between atomic lattices," explained Lounis. For his simulations of the scanning tunnelling experiment, he used the supercomputer known as JUMP in the Jülich Supercomputing Centre.

In a related article in the "Perspectives" section of "Science", the innovative approach is praised. A scanning tunnelling microscope is primarily used to characterise the surface of a sample. Thanks to the theoretical work in Jülich, it can now be used to gain a direct insight into the bulk of solids and to understand interesting effects in the nanoworld.

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Journal reference:

1. Weismann et al. Seeing the Fermi Surface in Real Space by Nanoscale Electron Focusing. Science, 2009; 323 (5918): 1190 DOI: 10.1126/science.1168738

Chemistry researchers at the University of Warwick have found that tiny nanoparticles could be twice as likely to stick to the interface of two non mixing liquids than previously believed. This opens up a range of new possibilities for the uses of nanoparticles in living cells, polymer composites, and high-tech foams, gels, and paints. The researchers are also working on ways of further artificially enhancing this new found sticking power.

University of Warwick researchers reviewed molecular simulations of the interaction between a non-charged nanoparticle and an "ideal" liquid-liquid interface. They were surprised to find that very small nanoparticles (of around 1 to 2 nanometres) varied considerably in their simulated ability to stick to such interfaces from what was expected in the standard model.

The researchers found that it took up to 50 percent more energy to dislodge the particles from the liquid-liquid interface for the smallest particle sizes. However as the radius of the particles increased this deviation from the standard model gradually faded out.

The researchers, Dr ir Stefan A. F. Bon and Dr David L. Cheung, believe that previous models failed to take into account the action of "capillary waves" in their depiction of the nanoparticles behaviour at the liquid to liquid interfaces.

Dr ir Stefan A. F. Bon said, " This new understanding on the nano-scale gives us much more flexibility in the design of everything from high-tech composite materials, to the use of quantum dots, cell biochemistry, and the manufacture of new "armored" polymer paint particles."

The researchers are now working on ways to build on this newly found natural stickiness of nanoparticles by designing polymer nanoparticles with opposing hydrophobic and hydrophilic surfaces that will bind even more strongly at oil/water liquid interfaces.

The research was funded by the Engineering and Physical Sciences Research Council (EPSRC)

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Journal reference:

1. Cheung et al. Interaction of Nanoparticles with Ideal Liquid-Liquid Interfaces. Physical Review Letters, 2009; 102 (6): 066103 DOI: 10.1103/PhysRevLett.102.066103

FEB 25,2009
A new facility opening later this year at the Diamond synchrotron is set to revolutionise world heritage science. A new research platform soon to be available at the leading UK science facility, Diamond Light Source, will help uncover ancient secrets that have been locked away for centuries. For the first time ever, cultural heritage scientists will be able to scan and image large relics and artifacts up to two tonnes in weight in incredible precision. They will no longer be restricted to examining small items.

Speaking at the AAAS Meeting in Chicago Dr Jen Hiller, Diamond's resident archaeologist, announced that the UK synchrotron will open a powerful new experimental station this autumn. Called the Joint Engineering, Environmental and Processing (JEEP) beamline, it will carry out experiments in a variety of areas including the growing field of world heritage science.

Dr Hiller explains, "Heritage scientists across the world are able to apply to use this unique beamline to delve deep inside precious ancient artifacts to unravel their secrets in a non-invasive way. Never before has it been possible to scan and image such large relics with such precision. Now is the time for researchers in this field to maximise this unique opportunity and consider how JEEP can help to advance their studies. "

"Thanks to the intensity of the X-rays produced by JEEP and its flexible space, researchers will be able to obtain a much higher resolution image, down to the scale of a few microns (less than the width of a human hair), and in significantly less time than the existing methods; we are talking about a matter of minutes as opposed to a number of hours. This finely detailed picture will enable scientists to see right inside an artifact helping them to obtain crucial information to piece together the story of its origin and history." continues Dr Hiller.

Eagerly awaiting the arrival of JEEP is Dr Janet Ambers, a scientist from the Conservation and Scientific Research Department at the British Museum. Along with her team Dr Ambers is currently studying a group of half life-sized Egyptian bronze statues. Until now they have only been able to examine them in a limited amount of detail leaving many questions unanswered. Diamond's JEEP beamline is set to change that.

Dr Ambers says, "We know that these statues are made up of a number of different parts that have been joined together. The joins are so dense that it is only by using JEEP's intense X-rays that we will be able to penetrate them and see how the statues were made. This will help to answer questions about the technology and materials used to originally produce the statues as well as provide information on how they were modified during 19th century restoration work. We are very excited about having access to this innovative tool because it will allow us to look at our artefacts in a completely new way."

Current analytical methods used by scientists at the British Museum allow them to produce standard 'X-rays' of objects using a static industrial X-ray tube. Alternatively, using a medical facility it is possible to perform a CT scan for relatively light objects. But both of these methods are limited in their precision and the amount of detail that they can provide. The former is incapable of creating a 3D image and the latter is suitable only for non-metallic objects. Neither method can deal with large heavy objects.

Dr Michael Drakopoulos, the Principal Beamline Scientist for JEEP, says, "The versatility of JEEP will open up exciting new opportunities in many fields of science due to its extremely high flux, high energy X-ray beam and its two complementary experimental areas. The larger area coming on line in Spring 2010, will be situated outside, further away from the X-ray source, allowing for a whole new range of exciting experiments currently not possible anywhere else in the world. It's fantastic that JEEP can help not only towards major advances in the environmental sciences and the world of engineering but also can have an extremely positive impact within the field of world heritage science."

Developments like JEEP are crucial to the growing field of heritage science in the UK. This was recently demonstrated by the creation of the Science and Heritage Programme, an £8 million five year research plan funded by the Arts and Humanities Research Council (AHRC) and Engineering and Physical Sciences Research Council (EPSRC) and supported by Research Councils UK. The programme takes forward recommendations made by the House of Lords Science and Technology Select Committee report on science and heritage of November 2006. This concluded that there was a compelling need for a comprehensive national strategy for heritage science. The vision of the Science and Heritage Programme is to increase knowledge and the resilience of our cultural heritage in the face of twenty-first-century challenges.

Combined with techniques available at other complementary facilities, cultural heritage research carried out at the Diamond synchrotron and the advances in the tools it provides will help the UK to maintain its position as one of the world leaders in the field of world heritage science.

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FEB 25,2009
Graphene, a single-atom-thick sheet of carbon, holds remarkable promise for future nanoelectronics applications. Whether graphene actually cuts it in industry, however, depends upon how graphene is cut, say researchers at the University of Illinois.

Graphene consists of a hexagonal lattice of carbon atoms. While scientists have predicted that the orientation of atoms along the edges of the lattice would affect the material's electronic properties, the prediction had not been proven experimentally.

Now, researchers at the U. of I. say they have proof.

"Our experimental results show, without a doubt, that the crystallographic orientation of the graphene edges significantly influences the electronic properties," said Joseph Lyding, a professor electrical and computer engineering. "To utilize nanometer-size pieces of graphene in future nanoelectronics, atomically precise control of the geometry of these structures will be required."

Lyding and graduate student Kyle Ritter (now at Micron Technology Inc. in Boise, Idaho) report their findings in a paper accepted for publication in Nature Materials online Feb. 15.

To carry out their work, the researchers developed a method for cutting and depositing nanometer-size bits of graphene on atomically clean semiconductor surfaces like silicon.

Then they used a scanning tunneling microscope to probe the electronic structure of the graphene with atomic-scale resolution.

"From this emerged a clear picture that edges with so-called zigzag orientation exhibited a strong edge state, whereas edges with armchair orientation did not," said Lyding, who also is affiliated with the university's Beckman Institute and the Micro and Nanotechnology Laboratory.

"We found that pieces of graphene smaller than about 10 nanometers with predominately zigzag edges exhibited metallic behavior rather than the semiconducting behavior expected from size alone," Lyding said. "This has major implications in that semiconducting behavior is mandatory for transistor fabrication."

Unlike carbon nanotubes, graphene is a flat sheet, and therefore compatible with conventional fabrication processes used by today's chipmakers. But, based on the researchers' experimental results, controlled engineering of the graphene edge structure will be required for obtaining uniform performance among graphene-based nanoelectronic devices.

"Even a tiny section of zigzag orientation on a 5-nanometer piece of graphene will change the material from a semiconductor into a metal," Lyding said. "And a transistor based on that, will not work. Period."

The Office of Naval Research and the National Science Foundation funded the work.

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Journal reference:

1. Kyle A. Ritter, Joseph W. Lyding. The influence of edge structure on the electronic properties of graphene quantum dots and nanoribbons. Nature Materials, 2009; 8 (3): 235 DOI: 10.1038/nmat2378