University of Virginia lab micro-sizes genetics testing

Caption: James Landers shows his DNA testing device. Credit: University of Virginia. Usage Restrictions: None.

Using new "lab on a chip" technology, James Landers hopes to create a hand-held device that may eventually allow physicians, crime scene investigators, pharmacists, even the general public to quickly and inexpensively conduct DNA tests from almost anywhere, without need for a complex and expensive central laboratory.

"We are simplifying and miniaturizing the analytical processes so we can do this work in the field, away from traditional laboratories, with very fast analysis times, and at a greatly reduced cost," said Landers, a University of Virginia professor of chemistry and mechanical engineering and associate professor of pathology.

Landers published a review this month of his research and the emerging field of lab-on-a-chip technology in the journal Analytical Chemistry.

"This area of research has matured enough during the last five years to allow us to seriously consider future possibilities for devices that would allow sample-in, answer-out capabilities from almost anywhere," he said.

Landers and a team of researchers at U.Va., including mechanical and electrical engineers, with input from pathologists and physicians, are designing a hand-held device — based on a unit the size of a microscope slide — that houses many of the analytical tools of an entire laboratory, in extreme miniature. The unit can test, for example, a pin-prick-size droplet of blood, and within an hour provide a DNA analysis.

"In creating these automated micro-fluidic devices, we can now begin to do macro-chemistry at the microscale," Landers said.

Such a device could be used in a doctor's office, for example, to quickly test for an array of infectious diseases, such as anthrax, avian flu or HIV, as well as for cancer or genetic defects. Because of the quick turn-around time, a patient would be able to wait only a short time on-site for a diagnosis. Appropriate treatment, if needed, could begin immediately.

Currently, test tube-size fluid samples are sent to external labs for analysis, usually requiring a 24- to 48-hour wait for a result.

"Time is of the essence when dealing with an infectious disease such as meningitis," Landers said. "We can greatly reduce that test time, and reduce the anxiety a patient experiences while waiting."

Landers said the research also dovetails with the trend toward "personalized medicine," in which medical care increasingly is tailored to the specific genetic profile of a patient. Such highly specialized personalized care can allow physicians to develop specific therapies for patients who might be susceptible to, for example, particular types of cancers.

Simplifying genetic testing, and reducing the costs of such tests, could help pave the way toward routine delivery of such personalized care based on an individual's genetic profile.

Hand-held micro labs also would be useful to crime scene investigators who could collect and analyze even a tiny sample of blood or semen on-site, enter the finding into a genetic database, and possibly identify the perpetrator very shortly after a crime has occurred.

Likewise, agricultural biotechnologists could do very rapid genetic analysis on thousands of hybrid plants that have desirable properties such as drought and disease resistance, Landers said.

"We can now do lab work in volumes that are thousands of times smaller than would normally be used in a regular lab setup, and can do it up to 100 times faster," he said. "As we improve our techniques and capabilities, the costs of fabricating these micro-analysis devices will drop enough to employ them routinely in a wide variety of settings."

Landers even envisions home DNA test kits, possibly available for purchase from pharmacies, that would allow individuals to self-test for flu or other diseases. ###

His colleagues at U.Va. include Mathew Begley, professor of mechanical engineering, Molly Hughes, assistant professor of internal medicine, and Sanford Feldman, director of the Center for Comparative Medicine.

Contact: James Landers jpl5e@virginia.edu 434-243-8658 University of Virginia

Tags: Nano or Nanotechnology and Nanotech

NSF and EPA establish 2 centers for environmental implications of nanotechnology

This image shows a "heat map" with increased (red) or decreased (green) stem cell growth. Silica nanoparticles bind to bacteria in this CEIN image. Credit: April Pyle, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA. Usage Restrictions: None.

Centers will focus on environmental effects of nanotechnology and its applications The National Science Foundation (NSF) and the U.S. Environmental Protection Agency (EPA) have made awards to establish two Centers for the Environmental Implications of Nanotechnology (CEIN). The centers, led by UCLA and Duke University, will study how nanomaterials interact with the environment and with living systems, and will translate this knowledge into risk assessment and mitigation strategies useful in the development of nanotechnology.

"The new centers will provide national and international leadership in the emerging field of environmental nanoscience," said Arden L. Bement, Jr., NSF director. "This is an important addition to the National Nanotechnology Initiative, and builds on earlier discoveries on the environmental implications of nanotechnology made since 2001, when NSF's Center for Biological and Environmental Technologies was established. The new centers are aimed at strengthening our nation's commitment to research on the environmental, health and safety implications of nanomaterials."

Microscope image of silicon dioxide nanoparticles. CEIN scientists will use new tools to discover the possible environmental impacts of nanoparticles. Credit: Eric M. V. Hoek, California NanoSystems Institute, UCLA.

The centers will work as a network, connected to other research organizations, industry and government agencies and will emphasize interdisciplinary research and education. Their challenge is to better integrate materials science and engineering with molecular, cellular, organismal and ecological biology and environmental science. "The collaborative approach that these centers will use is key to quickly building the scientific foundation for understanding the health and environmental implications of nanomaterials,"

said George Gray, EPA assistant administrator for research and development. "This comprehensive research model promises to augment the knowledge we need to be good stewards of the environment."

The Berkeley Pit in Butte, Mont., contains heavy metals contaminated with mineral nanoparticles. Credit: Mike Hochella, Virginia Tech.

Nanoparticles are as much as a million times smaller than the head of a pin, and have unusual properties compared with larger objects made from the same material. These unusual properties make nanomaterials attractive for use in everything from computer hard-drives to sunscreens, cosmetics and medical technologies. With the rapid development of nanotechnology and its applications, a wide variety of nanomaterials are now used in clothing, electronic devices, cosmetics, pharmaceuticals and other biomedical products.

The potential interactions of nanomaterials with living systems and the environment have attracted increasing attention from the public as well as manufacturers of nanomaterial based products, academic researchers, and policy makers. Nanotechnology is expected to become a $1 trillion industry within the next decade.

However, the environmental implications of these materials are only beginning to be understood.

The UCLA CEIN, to be housed at the California NanoSystems Institute on the UCLA campus, will explore the impact of nanomaterials on the environment and on interactions with biological systems at all scales from cellular to ecosystem.

At the Duke University CEIN, researchers plan to define the relationship between a vast array of nanomaterials--from natural to man-made to incidental, byproduct nanoparticles--and their potential environmental exposure, biological effects and ecological consequences. Nanomaterials that are already in commercial use as well as several present in nature will be among the first materials studied.

"We are deeply committed to insuring that nanotechnology is introduced and implemented in a responsible and environmentally-compatible manner," said André Nel, Chief of the Division of NanoMedicine at UCLA, who will serve as the UCLA center's director. "We see the UC CEIN as providing an important service to our nation and beyond."

Traditional toxicity testing relies mainly on a complex set of whole-animal-based toxicity testing strategies. "This approach cannot handle the rapid pace at which nanotechnology-based enterprises are generating new materials and ideas," said Nel, who is also the Director of the UC led-Campus Nanotoxicology Research and Training Program at UCLA.

"The CEIN's development of a comprehensive computational risk ranking will allow powerful risk predictions to be made by and for the academic community, industry, the public, and regulating agencies."

At Duke University, "a distinctive element will be the synthesis of information about nanoparticles into a rigorous risk assessment framework, the results of which will be transferred to policy-makers and society at large," said Duke CEIN director Mark Wiesner, Professor of Civil and Environmental Engineering at Duke's Pratt School of Engineering. Wiesner specializes in nanoparticle movement and transformation in the environment.

The Duke research team brings together internationally recognized leaders in environmental toxicology and ecosystem biology; nanomaterial transport, transformation and fate in the environment; biogeochemistry of nanomaterials and incidental airborne particulates; nanomaterial chemistry and fabrication; and environmental risk assessment, modeling and decision sciences.

A major effort for the research team over the coming year is to develop 32 tightly instrumented ecosystems in the Duke Forest in Durham, N.C. Known as mesocosms, these living laboratories provide areas where researchers can add nanoparticles and study the resulting interactions and effects on plants, fish, bacteria and other elements.

"This mesocosm facility will be the nano-environment equivalent of the space station--a unique resource with tremendous potential that will be tapped by researchers throughout the center and beyond," said Wiesner.

"This research will address the influence of nanomaterials on processes ranging from the subcellular to whole ecosystems."

While UCLA serves as the lead campus for the UC CEIN, researchers from a range of other institutions and organizations are involved in UCLA CEIN research, including UC Santa Barbara (UCSB), UC Davis (UCD), UC Riverside (UCR), Columbia University (New York),University of Texas (El Paso, TX), Nanyang Technological University (NTU, Singapore), the Molecular Foundry at Lawrence Berkeley National Laboratory (LBNL), Lawrence Livermore National Laboratory (LLNL), Sandia National Laboratory SNL), the University of Bremen (Germany), University College Dublin (UCD, Ireland) and the Universitat Rovira i Virgili (URV, Spain).

Duke CEIN deputy director Gregory Lowry from Carnegie Mellon University and co-principal investigator Kimberly Jones from Howard University specialize in nanoparticle movement and transformations in the environment. Mike Hochella, a nanogeochemist from Virginia Tech, and Rich Di Giulio, an ecotoxicologist from Duke are also co-principal investigators. Rounding out the team are collaborators Gordon Brown, a geochemist from Stanford University and Paul Bertsch, a soil scientist from the University of Kentucky.

Additional investigators affiliated with the Duke center include those at Clemson, and North Carolina State Universities, as well as scientists at the Environmental Protection Agency, Pacific Northwest National Laboratory, National Institute of Environmental Health Sciences, Army Corps of Engineers and the National Institute of Standards and Technology. International institutions collaborating with the Duke center include the European Center for Research and Education in Geosciences and the Environment; Sciences Po; Buenos Aires Institute of Technology; Nankai University; Swiss Federal Laboratories for Materials Testing and Research; Swiss Federal Institute of Aquatic Science and Technology; and the Institute of Occupational Medicine, United Kingdom. ###

Contact: Cheryl Dybas cdybas@nsf.gov 703-292-7734 National Science Foundation

Tags: Nano or Nanotechnology and Nanotech

Andre Nel, M.B.Ch.B., Ph.D. - Chief, Division of NanoMedicine, California NanoSystems Institute Professor, Medicine. Director, UC NanoToxicology Research Training Program Member, California NanoSystems Institute, JCCC Signal Transduction and Therapeutics Program Area

UCLA, partners establish new center on environmental effects of nanotechnology, Center based at UCLA's California NanoSystems Institute gets $24 million from EPA, NSF to focus on nanomaterials safety and risk assessment. UCLA and 12 collaborating institutions have been awarded $24 million in federal funding to establish the University of California Center for Environmental Implications of Nanotechnology (UC CEIN), which will help researchers design safer and more environmentally benign nanomaterials. The center, to be housed at the California NanoSystems Institute (CNSI) on the UCLA campus, will explore the impact of nanomaterials on life forms and the interactions of these materials with various biological systems and ecosystems.

Funding was awarded by the National Science Foundation and the U.S. Environmental Protection Agency following a highly competitive application and review process.

With the rapid development of nanotechnology and its applications, a wide variety of nanomaterials are now used in clothing, electronic devices, cosmetics, and pharmaceuticals and other biomedical products. The potential interactions of nanomaterials with living systems and the environment have attracted increasing attention from the public, as well as from manufacturers of nanomaterial-based products, academic researchers and policymakers. Nanotechnology is expected to become a $1 trillion industry within the next decade.

"UCLA and its partners are blazing the way to a brighter future through discoveries in nanotechnology that enhance our quality of life," UCLA Chancellor Gene Block said. "UCLA's selection as the headquarters of the University of California Center for Environmental Implications of Nanotechnology cements the campus's position as a leader in this critical emerging field and helps to ensure the introduction of often breathtaking nanotechnology in a manner consistent with our social and environmental values."

"We are deeply committed to ensuring that nanotechnology is introduced and implemented in a responsible and environmentally compatible manner," said Dr. André E. Nel, chief of the division of nanomedicine at UCLA, who will serve as the new center's director. "We see the UC CEIN as providing an important service to our nation and beyond, specifically to the National Science Foundation and the Environmental Protection Agency, and to industry at large."

Arturo Keller, a professor at the Donald Bren School of Environmental Science and Management at the University of California, Santa Barbara, will serve as the center's associate director. Co-principal investigators on the center's research executive committee include Hilary Godwin, of the UCLA Department of Environmental Health Sciences; Yoram Cohen, of the UCLA Department of Chemical and Biomolecular Engineering; and Roger Nisbet, of the UC Santa Barbara Department of Ecology, Evolution and Marine Biology.

The UC CEIN will employ approaches that differ from traditional toxicity testing, which relies mainly on a complex set of whole-animal-based testing strategies.

"This approach cannot handle the rapid pace at which nanotechnology-based enterprises are generating new materials and ideas," said Nel, who is also director of the UC Lead Campus Program for Nanotoxicology Research and Training, at UCLA. "The CEIN's development of a comprehensive computational risk ranking will allow powerful risk predictions to be made by and for the academic community, industry, the public and regulating agencies."

Establishing a predictive science of nanomaterials toxicity is an important and timely approach for nanotechnology-based enterprises wishing to avoid the problems faced by the chemical industry, where only a few hundred of the approximately 40,000 industrial chemicals have undergone toxicity testing, making it very challenging to control the toxicological impact of chemicals in the environment.

Building on this seminal concept, the UC CEIN brings together a highly integrated, multidisciplinary, synergistic team with the skills set to address the complexities of environmental science, ecotoxicity, materials science, nanotechnology, the biological mechanisms of injury, and the fate and transport of nanomaterials.

The UC CEIN will serve a critical national need to further understanding of the environmental health and safety of nanomaterials. The CNSI at UCLA will serve as the major base of operations for the new center, with a second major hub at UC Santa Barbara.

"The new centers will provide national and international leadership in the emerging field of environmental nanoscience," said Arden L. Bement Jr., director of the National Science Foundation. "This is an important addition to the National Nanotechnology Initiative and builds on earlier discoveries on the environmental implications of nanotechnology, made since 2001, when the NSF's Center for Biological and Environmental Technologies was established. The new centers are aimed at strengthening our nation's commitment to research on the environmental, health and safety implications of nanomaterials."

"The collaborative approach that these centers will use is key to quickly building the scientific foundation for understanding the health and environmental implications of nanomaterials," said George Gray, the Environmental Protection Agency's assistant administrator for research and development. "This comprehensive research model promises to augment the knowledge we need to be good stewards of the environment."

The UC CEIN will unite recognized experts in the fields of engineering, chemistry, physics, materials science, ecology, cell biology, marine biology, bacteriology, particle and chemical toxicology, computer modeling, high-throughput screening, and risk prediction to establish the foundation of a new scientific discipline: environmental nanotechnology and nanotoxicology.

"A significant part of our mission is to use the insights gained from the research conducted at the UC CEIN to inform policy decisions about the safe implementation of nanotechnology," said UCLA's Godwin, who will head the center's education and outreach initiatives. "As a result, we are planning activities to engage a wide range of stakeholders — including journalists, policymakers and the general public — in UC CEIN activities."

The center's seven integrated research groups will be led by UC Santa Barbara's Keller; UCLA's Cohen; Eric Hoek, of the UCLA Department of Civil and Environmental Engineering; Patricia Holden, of the UC Santa Barbara Department of Environmental Microbiology at the Donald Bren School of Environmental Science and Management; Hunter Stanton Lenihan, of the UC Santa Barbara Department of Applied Marine Ecology, Coastal Marine Resources Management at the Bren School; Kenneth Bradley, of the UCLA Department of Microbiology, Immunology and Molecular Genetics; and Barbara Herr Harthorn, director of the Center for Nanotechnology in Society at UC Santa Barbara.

"The nanomaterials industry continues to grow rapidly, both nationally and internationally, and it behooves us to learn from past experience in the area of chemical hazard management," Nel said. "The team has very strong and broad experience in collaborative nanomaterials and nanoscience research and has the potential to deliver an expert system to design new materials that are both safe and effective." ###

In addition to those at UCLA and UC Santa Barbara, researchers from a broad range of other institutions and organizations are involved in the UC CEIN, including UC Davis, UC Riverside, Columbia University, the University of Texas–El Paso, Singapore's Nanyang Technological University, the Molecular Foundry at Lawrence Berkeley National Laboratory, Lawrence Livermore National Laboratory, Sandia National Laboratory, Germany's University of Bremen, University College Dublin, and Spain's Universitat Rovira i Virgili.

The California NanoSystems Institute is an integrated research center operating jointly at UCLA and UC Santa Barbara whose mission is to foster interdisciplinary collaborations for discoveries in nanosystems and nanotechnology; train the next generation of scientists, educators and technology leaders; and facilitate partnerships with industry, fueling economic development and the social well-being of California, the United States and the world. The CNSI was established in 2000 with $100 million from the state of California and an additional $250 million in federal research grants and industry funding.

At the institute, scientists in the areas of biology, chemistry, biochemistry, physics, mathematics, computational science and engineering are measuring, modifying and manipulating the building blocks of our world — atoms and molecules. These scientists benefit from an integrated laboratory culture enabling them to conduct dynamic research at the nanoscale, leading to significant breakthroughs in the areas of health, energy, the environment and information technology. For additional information, visit www.cnsi.ucla.edu.

UCLA is California's largest university, with an enrollment of nearly 37,000 undergraduate and graduate students. The UCLA College of Letters and Science and the university's 11 professional schools feature renowned faculty and offer more than 300 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Four alumni and five faculty have been awarded the Nobel Prize.

Tags: Nano or Nanotechnology and Nanotech

NSF funds multi-university center to study environmental implications of nanotechnology

Caption: Dissolution of an nC60 aggregate by sodium acetate. Credit: Peter Vikesland, Virginia Tech. Usage Restrictions: with coverage of research by Peter Vikesland and/or of the announcement of the NSF-funded Center for the Environmental Implications of Nanotechnology.

Blacksburg, Va. – Researchers from geosciences and civil and environmental engineering at Virginia Tech are part of a consortium of four principal universities and five other schools awarded a multi-million dollar grant to study nanotechnology and the environment. This is one of only two such consortiums funded by the National Science Foundation (NSF) to form a national Center for the Environmental Implications of Nanotechnology (CEIN). Total funding for the project is $14 million over five years with an opportunity to renew for another five. Nanoparticles are as much as a million times smaller than the head of a pin, and have unusual properties compared with larger objects made from the same material.

These unusual properties make nanomaterials attractive for use in everything from computer hard-drives to sunscreens, cosmetics and medical technologies. However, the environmental implications of these materials are virtually unknown.

Headquartered at Duke University, the CEIN will integrate the expertise of researchers in fields such as ecology, cell and molecular biology, geochemistry, environmental engineering, nanochemistry, and social science. In addition to Virginia Tech and Duke, the other schools involved in the project are Carnegie Mellon University and Howard University, with the University of Kentucky and Stanford University playing smaller but also important roles. The other CEIN named in the grant is headquartered at the University of California, Los Angeles (UCLA) and includes UC Santa Barbara. The centers are charged with studying the behavior of nanomaterials and helping to assess existing and future concerns surrounding their environmental implications.

"This is a grand challenge," said Michael Hochella, University Distinguished Professor of Geosciences at Virginia Tech, one of five lead investigators in the consortium. "The potential diversity of nanomaterials is staggering, with countless variations in size, shape, surface chemistry, chemical composition, coatings and composites. Our challenge is to unravel the role of nanoparticles—both manufactured and naturally occurring—in ecosystems, their movements through the environment, their interactions with organisms, the mechanism by which they exert their influence and thus, their environmental impacts." Other researchers from Virginia Tech involved in the project are Linsey Marr and Peter Vikesland, both associate professors in civil and environmental engineering and NSF Career Award recipients.

Caption: Surface waters that drain this area contain heavy metal contaminated mineral nanoparticles. Such environmental nanoparticles contribute to the transport of these metals up to 500 km downstream. Inset: TEM image of mineral nanoparticles found in the Clark Fork River. Credit: Courtesy of Michael Hochella, Virginia Tech Usage Restrictions: With coverage of the research by Dr. Hochella and/or announcement of the new NSF-funded Center for the Environmental Implications of Nanotechnology

A distinctive element of the center is the synthesis of the data into a risk assessment model and to transfer the results into the policy-making community and society at large. The center will place students at the center of the collaborative process between schools. Virginia Tech's part of the program includes undergraduate and graduate student fellowships, undergraduate research grants, seminar series, internships, lab rotations, service learning opportunities and annual workshops. In addition, the project will utilize recruitment efforts that will establish a diverse cadre of graduate students of underrepresented minorities and women. Howard University's status as a Historically Black College and University makes it a valuable asset in the recruitment process.

Outreach is another key component of the CEIN. The center will develop educational tools for high school science teachers as well as curricula for partner museums, 4-H council, and other learning venues. Also a critical part of the project is to foster dialog with policy makers, regulators, government, and industry. The center's social science aspect will focus on creating an infrastructure that supports this type of engagement and understanding of science on the nano scale.

"We are very, very fortunate to have been awarded this grant," Hochella said. "The list of world-class universities that applied but were not awarded this center is truly sobering. The expertise and facilities of our CEIN will now enable us to respond to emerging challenges, develop fundamental knowledge and the human resources across disciplines, and engage society to ensure that nanotechnology emerges as a tool of sustainability." ###

About the College of Science

The College of Science at Virginia Tech gives students a comprehensive foundation in the scientific method. Outstanding faculty members teach courses and conduct research in biology, chemistry, economics, geosciences, mathematics, physics, psychology, and statistics. The college is dedicated to fostering a research intensive environment and offers programs in many cutting edge areas, including those in nanotechnology, biological sciences, information theory and science, and supports the university's research initiatives through the Institute for Critical Technologies and Applied Sciences, and the Institute for Biomedical and Public Health Sciences. The College of Science also houses programs in intellectual property law and pre-medicine.

About the College of Engineering

The College of Engineering at Virginia Tech is internationally recognized for its excellence in 14 engineering disciplines and computer science. The college's 5,600 undergraduates benefit from an innovative curriculum that provides a "hands-on, minds-on" approach to engineering education, complementing classroom instruction with two unique design-and-build facilities and a strong Cooperative Education Program. With more than 50 research centers and numerous laboratories, the college offers its 2,000 graduate students opportunities in advanced fields of study such as biomedical engineering, state-of-the-art microelectronics, and nanotechnology.

About Virginia Tech

Founded in 1872 as a land-grant college, Virginia Tech has grown to become among the largest universities in the Commonwealth of Virginia. Today, Virginia Tech's eight colleges are dedicated to putting knowledge to work through teaching, research, and outreach activities and to fulfilling its vision to be among the top research universities in the nation. At its 2,600-acre main campus located in Blacksburg and other campus centers in Northern Virginia, Southwest Virginia, Hampton Roads, Richmond, and Roanoke, Virginia Tech enrolls more than 28,000 full- and part-time undergraduate and graduate students from all 50 states and more than 100 countries in 180 academic degree programs.

Contact: Catherine Doss cdoss@vt.edu 540-231-5035 Virginia Tech

Tags: Nano or Nanotechnology and Nanotech

New technique sees into tissue at greater depth, resolution

Joseph Izatt

DURHAM, N.C. – By coupling a kicked-up version of microscopy with miniscule particles of gold, Duke University scientists are now able to peer so deep into living tissue that they can see molecules interacting. If future studies in animal models prove fruitful, the researchers believe that their new approach can have a wide spectrum of clinical applications, from studying the margins of a tumor as it is removed from the body to assessing the effects of anti-cancer agents on the blood vessels that nourish tumors.

The Duke bioengineers combined tightly focused heat with optical coherence tomography (OCT), which has often been called the optical equivalent of ultrasound. OCT is commonly used in medical clinics where imaging at the highest resolution is critical, such as in the retina. These experiments represent the first time the technique has been extended to the functional imaging of cells expressing particular molecular receptors.

"This technique could possibly augment traditional methods of deep-tissue molecular imaging with a relatively high resolution," said Melissa Skala, a postdoctoral fellow working in the laboratory of Joseph Izatt, professor of biomedical engineering in Duke's Pratt School of Engineering. "Not only were we able to get better images, we were able to specifically target the types of cells we were looking for."

Melissa Skala

The results of the Duke research were posted on line by Nano Letters, a journal published by the American Chemical Society. The research was supported by the National Institutes of Health.

For their experiments, the Duke team attached nanospheres of gold to a targeting molecule known as a monoclonal antibody.

Gold is a metal that not only is an efficient conductor of heat, but whose effects in the body are well known. The antibody they used targets epidermal growth factor receptor (EGFR), a cell-surface receptor implicated in cancer.

These "tagged" antibodies were then applied to the surface of a three-dimensional tissue model composed of human cells – both cancerous and non-cancerous. Skala hoped that these antibodies would home in on cells that were overproducing EGFR on their surfaces, an indicator of cancerous activity. Then the photothermal OCT would be able to detect them by showing where the gold spheres were concentrated.

"When we directed the photothermal OCT at the tissue, we found that the cells that were overexpressing EGFR gave off a signal 300 percent higher than cells with low expressions of EGFR," Skala said.

Adding heat to this form of microscopy technique created a phenomenon much like that seen on very hot days, when portions of the pavement far in the distance seem to float or hover above the road.

"The heat causes a distortion in the way light is reflected off the gold nanospheres in a characteristic way," Skala explained. "As we changed the temperature, the light pathways would change in measurable ways."

In this manner, Skala explained, they were not only able to "see" cells within the tissue, but they were able to capture the molecular function of an antibody attaching to a receptor.

"The use of metal nanoparticles as contrast agents with photothermal OCT technology could lead to a host of potential clinical applications," Izatt said. "Organically-based contrast agents can cause damage or death to the targeted cells, while metal nanospheres are relatively safer."

"Also, given the wide range of nanoparticle shapes and sizes, coupled with the ability to 'tune" the optical wavelength of the OCT, we can customize our approach to many different target types," Izatt said.

Skala plans to expand the use of this approach in animal models to better understand the role of different cancer therapies. Tumors with elevated levels of EGFR are known to have a poor prognosis, and she plans to use photothermal OCT to measure how these tumor types react to different therapies. ###

Other members of the Duke team were Adam Wax, professor of biomedical engineering and his graduate student Matthew Crow. Skala also worked with Mark Dewhirst, a cancer researcher at Duke University Medical Center, and plans further collaborations with the Dewhirst laboratory to apply this technique better understand the fundamentals of cancer.

Contact: Richard Merritt richard.merritt@duke.edu 919-660-8414 Duke University

Tags: Nano or Nanotechnology and Nanotech

NC State engineers discover nanoparticles can break on through

Jan Genzer, Ph. D., Materials Science and Engineering, University of Pennsylvania (1996). Areas of Interest: Behavior of polymers at surfaces and interfaces, Polymer thermodynamics, Materials self-assembly. Email: jan_genzer@ncsu.edu. Research Group: scf.che.ncsu.edu/, Phone: 919-515-2069

In a finding that could speed the use of sensors or barcodes at the nanoscale, North Carolina State University engineers have shown that certain types of tiny organic particles, when heated to the proper temperature, bob to the surface of a layer of a thin polymer film and then can reversibly recede below the surface when heated a second time. Selectively bringing a number of particles to a surface and then sinking them back below it results in controllable surface patterns. According to NC State researchers involved in the project, patterning surfaces is one of the holy grails of current nanotechnology research, and is difficult to do with certain particles. They add that the finding could result in tiny reusable bar codes, or in small fluorescent features that turn off when they sense too much heat or the presence of a certain chemical.

Dr. Jan Genzer, professor of chemical and biomolecular engineering, and Dr. Richard Spontak, professor of chemical and biomolecular engineering and materials science and engineering, published their finding along with graduate students Arif Gozen and Bin Wei in the journal Nano Letters.

They worked with engineers who designed the unique particles at the University of Melbourne in Australia.

The researchers used a special type of organic nanoparticle called a core-shell microgel in which the core of a cross-linked, or networked, polymer is surrounded by a shell of a different polymer.

Richard J. Spontak, Professor, Ph.D., Chemical Engineering, University of California at Berkeley 1988, B.S., Chemical Engineering, Pennsylvania State University 1983. Areas of interest: Polymer morphology and phase stability, Multifunctional and nanostructured polymers, blends and networks. Application of microscopy techniques to polymer science and engineering. Email: Rich_Spontak@ncsu.edu, Phone: 919.515.4200

"Most polymers are chain-like macromolecules that are like very long, cooked spaghetti noodles, but these special core-shell particles are shaped more like squash balls of one polymer with a fuzzy surface of a different polymer," Spontak says. Heating these approximately 30-nanometer particles - which are hundreds of times smaller than a human hair - allows them to break through a polymer/polymer interface like a submarine coming to the surface of water. Reheating the particles at a polymer surface sinks them back below the surface. "This technique allows us to place the particles right where we want them - on the surface of a thin film," Genzer says. "It can be used to create a reusable bar code, for instance, or other functional polymer surfaces." ###

Note to editors: The abstract of the paper follows.

"Autophobicity-Driven Surface Segregation and Patterning of Core-Shell Microgel Nanoparticles"

Authors: Bin Wei, Arif O. Gozen, Richard J. Spontak and Jan Genzer, North Carolina State University; Paul A. Gurr, Anton Blencowe, David H. Solomon and Greg G. Qiao, University of Melbourne. Published: Online Aug. 8, 2008, in Nano Letters

Abstract: Core-shell microgel (CSMG) nanoparticles, also referred to as core-cross-linked star (CCS) polymers, can be envisaged as permanently cross-linked block copolymer micelles and, as such, afford novel opportunities for chemical functionalization, templating, and encapsulation. In this study, we explore the behavior of CSMG nanoparticles comprising a poly(methyl methacrylate) (PMMA) shell in molten PMMA thin films. Because of the autophobicity between the densely packed, short PMMA arms of the CSMG shell and the long PMMA chains in the matrix, the nanoparticles migrate to the film surface.

They cannot, however, break through the surface because of the inherently high surface energy of PMMA. Similar thermal treatment of CSMG-containing PMMA thin films with a polystyrene (PS) capping layer replaces surface energy at the PMMA/air interface by interfacial energy at the PMMA/PS interface, which reduces the energy barrier by an order of magnitude, thereby permitting the nanoparticles to emerge out of the PMMA bulk. This nanoscale process is reversible and can be captured at intermediate degrees of completion. Moreover, it is fundamentally general and can be exploited as an alternative means by which to reversibly pattern or functionalize polymer surfaces for applications requiring responsive nanolithography.

Contact: Mick Kulikowski mick_kulikowski@ncsu.edu 919-515-8387 North Carolina State University

Tags: Nano or Nanotechnology and Nanotech

CCNY receives $5 million NSF grant to establish center for nanostructure applications

Dr. Daniel L. Akins, Dr. Akins has been a Professor of Chemistry at The City College of New York since 1981, and director of the CUNY-Center for Analysis of Structure and Interfaces since 1988. He holds a doctorate in physical chemistry from the University of California at Berkeley, received in 1968.

NEW YORK, September 16, 2008 – The City College of New York (CCNY) announced today that it has received $5 million over five years from the National Science Foundation (NSF) to establish a new, interdisciplinary research center that will investigate new applications for nanostructures and nanomaterials in sensors and energy systems. Known as CENSES (Center for Exploitation of Nanostructures in Sensors and Energy Systems), the center will also investigate emerging technologies and novel characterization techniques for nanostructures and nanomaterials.

Dr. Daniel L. Akins, Distinguished Service Professor of Chemistry, will serve as the center's Director and Principal Investigator. Serving as co-Principal Investigators will be: Dr. Maria C. Tamargo, Professor of Chemistry; Dr. Alex Couzis, Professor of Chemical Engineering, and Dr. Swapan K. Gayan, Professor of Physics.

"CENSES will focus its efforts on addressing several of the major challenges facing the nation and the world, including sustainable energy technologies and monitoring of health, the environment and national security threats," said Professor Akins in announcing the grant. "Our objective is to become a national resource center for these areas and to collaborate on research and development efforts with a variety of potential partners."

Existing collaborations with the Nanoscale Science and Engineering Center at Columbia University and the Center for Sustainable Energy at Bronx Community College are being folded into the center, Professor Akins noted. The research efforts have been organized into three areas:

* Nanomaterials and nanostructures for sensor applications, headed by Professor Tamargo;
* Nanomaterials and nanostructures in energy systems, headed by Professor Couzis, and
* Emerging technologies and novel characterization techniques, headed by Professor Gayan.

However, Professor Akins pointed out that there are many synergistic opportunities between sensor and energy systems application since they can draw upon a "common pool of nanomaterial systems. Also, much of the research acumen will be derived from scientists engaged in projects in both areas," he added.

The grant will fund projects that potentially involve 21 professors and researchers from CCNY's Chemical Engineering, Chemistry, Electrical Engineering and Physics Departments. Eight full-time graduate students, eight undergraduate research positions and four postdoctoral fellows will be supported by the grant, as well. In addition, it will support several activities intended to integrate the research with education. These include:

* Establishing learning communities among graduate students based on the Peer-Led Team Learning model developed at CCNY and used in undergraduate chemistry classes.
* New online curricular courses for students and online courses for the public available through the CUNY School of Professional Studies.
* Extended international research visits for five students per year enabling them to travel to different countries for three-month assignments and become globally engaged researchers.
* Recruitment and retention strategies for students underrepresented in science and engineering. ###

About The City College of New York

For more than 160 years, The City College of New York has provided low-cost, high-quality education for New Yorkers in a wide variety of disciplines. Over 14,000 students pursue undergraduate and graduate degrees in the College of Liberal Arts and Sciences; The School of Architecture, Urban Design and Landscape Architecture (SAUDLA); The School of Education; The Grove School of Engineering, and The Sophie Davis School of Biomedical Education. For additional information, visit www.ccny.cuny.edu.

Contact: Ellis Simon esimon@ccny.cuny.edu 212-650-6460 City College of New York

Tags: Nano or Nanotechnology and Nanotech

Simulations help explain fast water transport in nanotubes

Photo by L. Brian Stauffer, Narayana R. Aluru, professor of mechanical science and engineering, left, and doctoral student Sony Joseph have discovered the physical mechanism behind the rapid transport of water in carbon nanotubes. Image in background shows the trajectory of water molecules in a carbon nanotube moving in the direction of their orientations due to rotation-translation coupling.

CHAMPAIGN, Ill. — By discovering the physical mechanism behind the rapid transport of water in carbon nanotubes, scientists at the University of Illinois have moved a step closer to ultra-efficient, next-generation nanofluidic devices for drug delivery, water purification and nano-manufacturing. "Extraordinarily fast transport of water in carbon nanotubes has generally been attributed to the smoothness of the nanotube walls and their hydrophobic, or water-hating surfaces," said Narayana R. Aluru, a Willett Faculty Scholar and a professor of mechanical science and engineering at the U. of I.

"We can now show that the fast transport can be enhanced by orienting water molecules in a nanotube," Aluru said. "Orientation can give rise to a coupling between the water molecules' rotational and translational motions, resulting in a helical, screw-type motion through the nanotube," Aluru said.

Using molecular dynamics simulations, Aluru and graduate student Sony Joseph examined the physical mechanism behind orientation-driven rapid transport. For the simulations, the system consisted of water molecules in a 9.83 nanometer long nanotube, connected to a bath at each end. Nanotubes of two diameters (0.78 nanometers and 1.25 nanometers) were used. Aluru and Joseph reported their findings in the journal Physical Review Letters.

For very small nanotubes, water molecules fill the nanotube in single-file fashion, and orient in one direction as a result of confinement effects. This orientation produces water transport in one direction. However, the water molecules can flip their orientations collectively at intervals, reversing the flow and resulting in no net transport.

In bigger nanotubes, water molecules are not oriented in any particular direction, again resulting in no transport.

Water is a polar molecule consisting of two hydrogen atoms and one oxygen atom. Although its net charge is zero, the molecule has a positive side (hydrogen) and a negative side (oxygen). This polarity causes the molecule to orient in a particular direction when in the presence of an electric field.

Creating and maintaining that orientation, either by directly applying an electric field or by attaching chemical functional groups at the ends of the nanotubes, produces rapid transport, the researchers report.

"The molecular mechanism governing the relationship between orientation and flow had not been known," Aluru said. "The coupling occurs between the rotation of one molecule and the translation of its neighboring molecules. This coupling moves water through the nanotube in a helical, screw-like fashion."

In addition to explaining recent experimental results obtained by other groups, the researchers' findings also describe a physical mechanism that could be used to pump water through nanotube membranes in next-generation nanofluidic devices. ###

Funding was provided by the National Science Foundation and the National Institutes of Health.

Aluru is affiliated with the U. of I.’s Beckman Institute, Micro and Nanotechnology Laboratory, and departments of bioengineering and of electrical and computer engineering.

Editor’s note: To reach Narayana Aluru, call 217-333-1180; e-mail: aluru@illinois.edu.

Contact: James E. Kloeppel kloeppel@illinois.edu 217-244-1073 University of Illinois at Urbana-Champaign

Tags: Nano or Nanotechnology and Nanotech

Improving our ability to peek inside molecules

Massively parallel holography at high resolutions.
a) A lithographic test sample imaged by scanning electron microscopy (SEM) next to a 30-nm-thick twin-prime 71 x 73 array with 44-nm square gold scattering elements. The scale bar is 2 mm. b) The diffraction pattern collected at the ALS (1 x 10 6 photons in a five second exposure, 200 mm from the sample). c) The real part of the reconstructed hologram. d) The simulation with 1 x 10 6 photons. The grey scale represents the real part of the hologram. e) A simulation with the same number of photons, but a single reference pinhole. f) Line through the two dots indicated in image c.

LIVERMORE -- It's not easy to see a single molecule inside a living cell.

Nevertheless, researchers at Lawrence Livermore National Laboratory are helping to develop a new technique that will enable them to create detailed high-resolution images, giving scientists an unprecedented look at the atomic structure of cellular molecules.

The LLNL team is collaborating with scientists across the country and in Germany and Sweden to utilize high-energy X-ray beams, combined with complex algorithms, to overcome difficulties in current technology.

The work began more than five years ago as a Laboratory Directed Research and Development (LDRD) project, headed by Stefano Marchesini. He has since transferred to Lawrence Berkeley Lab (LBNL), leaving the project in the hands of Stefan Hau-Riege, a materials science physicist at LLNL. For now, the Advanced Light Source at LBNL and the FLASH facility in Hamburg, Germany, are being used to provide the X-ray beams. But a new facility under construction at Stanford University, the Linac Coherent Light Source (LCLS), will provide additional capabilities and greater imaging accuracy when it comes on line next year. Another light source being built in Hamburg will be used as well. When completed in late 2013, the X-ray Free Electron Laser (XFEL) will be the world's longest artificial light source.

Experimental geometry and imaging, A coherent X-ray beam illuminates both the sample and a Uniformly Redundant Array (URA) placed next to it. An area detector (a charged-coupled device, CCD, in these experiments) collects the diffracted X-rays. The Fourier Transform of the diffraction pattern yields the autocorrelation map with a holographic term (in the circle) displaced from the centre. The Hadamard Transform decodes the hologram.

Using high-energy, extremely short-pulse - less than 100 femtoseconds, or one quadrillionth of a second - X-ray beams to examine nanoscale objects is not a new concept. The difficulty lies with the algorithms to convert the resulting patterns into usable images.

One method to increase the signal and resolution of the image is to include a second item with known features during the laser imaging. Known as a "reference object," it gives the researchers additional information with which to process the imaging data.

What is new is to use a very special reference object called a "uniformly redundant array" (URA). In this case, a combination of complex formulas known as a "Fourier Transform" and a "Hadamard Transform" are utilized to convert the data into an image that represents the object being examined. Hadamard transforms are commonly used in signal processing and data algorithms, including those used in photo and video compression.

According to Hau-Riege, "The resolution we achieved is among the best ever reported for holography of a micrometer-sized object, and we believe that it will improve in the future with the development of nano-arrays for Fourier Transform Holography at LCLS." ###

Other contributors to the findings include: Anton Barty, Matthias Frank, and Abraham Szöke, all from LLNL; researchers from LBNL; UC-Berkeley; Stanford University; Sweden's Uppsala University; the Centre for Free-Electron Laser Science at DESY in Hamburg, Germany; Arizona State University; and Princeton University.

Details of the study appear in the August 1 edition of the journal Nature Photonics.
www.nature.com/nphoton/journal/

Founded in 1952, Lawrence Livermore National Laboratory (https://www.llnl.gov) is a national security laboratory, with a mission to ensure national security and apply science and technology to the important issues of our time. Lawrence Livermore National Laboratory is managed by Lawrence Livermore National Security, LLC for the U.S. Department of Energy's National Nuclear Security Administration.

Contact: Bob Hirschfeld newsbob@llnl.gov 925-422-2379 DOE/Lawrence Livermore National Laboratory

Tags: Nano or Nanotechnology and Nanotech

New carbon material shows promise of storing large quantities of renewable electrical energy

Rod Ruoff, a mechanical engineering professor, poses in his lab at The University of Texas. Photos by: Beverly Barrett

AUSTIN, Texas— Engineers and scientists at The University of Texas at Austin have achieved a breakthrough in the use of a one-atom thick structure called “graphene” as a new carbon-based material for storing electrical charge in ultracapacitor devices, perhaps paving the way for the massive installation of renewable energies such as wind and solar power.

The researchers believe their breakthrough shows promise that graphene (a form of carbon) could eventually double the capacity of existing ultracapacitors, which are manufactured using an entirely different form of carbon.

“Through such a device, electrical charge can be rapidly stored on the graphene sheets, and released from them as well for the delivery of electrical current and, thus, electrical power,” says Rod Ruoff, a mechanical engineering professor and a physical chemist. “There are reasons to think that the ability to store electrical charge can be about double that of current commercially used materials. We are working to see if that prediction will be borne out in the laboratory.”

A model of charged graphene with oppositely charged ions (represented by ping pong balls), which occurs in an ultracapacitor.

Two main methods exist to store electrical energy: in re-chargeable batteries and in ultracapacitors which are becoming increasingly commercialized but are not yet as popularly known. An ultracapacitor can be used in a wide range of energy capture and storage applications and are used either by themselves as the primary power source or in combination with batteries or fuel cells. Some advantages of ultracapacitors over more traditional energy storage devices (such as batteries) include: higher power capability, longer life, a wider thermal operating range, lighter, more flexible packaging and lower maintenance, Ruoff says.

Ruoff and his team prepared chemically modified graphene material and, using several types of common electrolytes, have constructed and electrically tested graphene-based ultracapacitor cells. The amount of electrical charge stored per weight (called “specific capacitance”) of the graphene material has already rivaled the values available in existing ultracapacitors, and modeling suggests the possibility of doubling the capacity.

“Our interest derives from the exceptional properties of these atom-thick and electrically conductive graphene sheets, because in principle all of the surface of this new carbon material can be in contact with the electrolyte,” says Ruoff, who holds the Cockrell Family Regents Chair in Engineering #7. “Graphene’s surface area of 2630 square meters per gram (almost the area of a football field in about 1/500th of a pound of material) means that a greater number of positive or negative ions in the electrolyte can form a layer on the graphene sheets resulting in exceptional levels of stored charge.”

The U.S. Department of Energy has said that an improved method for storage of electrical energy is one of the main challenges preventing the substantial installation of renewable energies such as wind and solar power. Storage is vital for times when the wind doesn’t blow or the sun doesn’t shine. During those times, the stored electrical energy can be delivered through the electrical grid as needed.

Ruoff’s team includes graduate student Meryl Stoller and post-doctoral fellows Sungjin Park, Yanwu Zhu, and Jinho An, all from the Mechanical Engineering Department and the Texas Materials Institute at the university. Their findings will be published in the Oct. 8 edition of Nano Letters. The article was posted on the journal’s Web site this week.

This technology, Stoller says, has the promise of significantly improving the efficiency and performance of electric and hybrid cars, buses, trains and trams. Even everyday devices such as office copiers and cell phones benefit from the improved power delivery and long lifetimes of ultracapacitors.

Ruoff says significant implementation of wind farms for generation of electricity is occurring throughout the world and the United States, with Texas and California first and second in the generation of wind power.

According to the American Wind Energy Association, in 2007 wind power installation grew 45 percent in this country. Ruoff says if the energy production from wind turbine technology grew at 45 percent annually for the next 20 years, the total energy production (from wind alone) would almost equal the entire energy production of the world from all sources in 2007.

“While it is unlikely that such explosive installation and use of wind can continue at this growth rate for 20 years, one can see the possibilities, and also ponder the issues of scale,” he says. “Electrical energy storage becomes a critical component when very large quantities of renewable electrical energy are being generated.” ###

Funding and support was provided by the Texas Nanotechnology Research Superiority Initiative, The University of Texas at Austin and a Korea Research Foundation Grant for fellowship support for Dr. Park.

Ruoff's latest work to define the structure of graphite oxide appeared in the Sept. 26 issue of the journal Science. To read that story, go to: www.engr.utexas.edu/news/articles/.

For more information on Ruoff’s work, visit: bucky-central.me.utexas.edu/.

For more information, contact: Daniel J. Vargas, Cockrell School of Engineering, 512-471-7541, Daniel.vargas2@engr.utexas.edu; Rod Ruoff, Cockrell School of Engineering, 512-471-4691 or 847-370-4637, r.ruoff@mail.utexas.edu

About the Cockrell School of Engineering:

The Cockrell School ranks among the top ten engineering programs in the United States and aspires to move into the top five. With the nation's fourth highest number of faculty members elected to the National Academy of Engineering, the Cockrell School's more than 7,000 students work with many of the world's finest engineering educators and researchers. This environment prepares graduates to become engineering leaders and innovators working for the betterment of society.

Contact: Rod Ruoff r.ruoff@mail.utexas.edu 512-471-4691 University of Texas at Austin

Tags: Nano or Nanotechnology and Nanotech

New research center at Brandeis to combine materials science and biology

Robert Meyer, Ph.D. Professor of Physics, Complex Fluids, Ph.D., Harvard University Email Address: meyer@brandeis.edu Telephone: 781-736-2870 (Office) Fax: 781-736-2915 Office: Abelson-Bass-Yalem 216 Homepage: nematic.elsie.brandeis.edu/

Brandeis is smallest university to join elite group of universities with a materials research center Waltham, MA—Brandeis University has won a highly competitive $7.8 million grant from the National Science Foundation to establish a Materials Research Science and Engineering Center (MRSEC). The Center will study the effects of imposing constraints on materials, such as DNA confined in cells and the self-assembly of large arrays of rod-like virus particles, as a guide to engineering semiconductor nano-particles into shapes and forms suitable for applications such as biosensors and solar cells.

"Brandeis has been at the forefront of recent advances in materials science and biology, both in studying the properties of materials occurring in biological systems, and in understanding the role of material properties in the structure and function of cells and cellular components," said principal investigator Robert Meyer, a pioneer in the physics of liquid crystals.

The collaborative, interdisciplinary center will to try to produce a new category of materials known as "active matter." Distinct from normal inert materials such as plastics and steel, active matter can move on its own and exhibits properties previously only observed in living materials, such as muscle and cells.

"In general, we want to understand how biological gadgets are built out of materials, carefully structured and constrained, and from this to learn how to engineer functional bio-mimetic nano-systems for important applications," said Meyer.

The Brandeis center will involve physicists, biochemists, chemists, and biologists in a two-pronged approach to research. In a bottom-up approach, the researchers will explore how the addition of typical biological constraints, such as crowding and confinement, affects materials. For instance, DNA is a long polymer chain, confined to a small volume within a cell. How does this affect the dynamics of this molecule, for instance in division of an e.coli bacterium into two daughter cells? Likewise, the scientists want to understand how tethers added to the DNA in a cell nucleus affect how it can move to carry out important genetic processes.

In a top-down approach, the researchers will explore functioning cellular components, such as cilia, the organelles that miraculously move in synchronization to perform their jobs, such as keeping the lungs clear of pollutants. The researchers will essentially reverse engineer the function and structure of such "biological gadgets."

"Cilia are living machines that we're going to study by a combination of 3D electron microscopy, single particle experimentation, and genetic modification," explained Meyer. "We can genetically modify the structure of cilia, measure those changes with electron microscopy, and correlate them with the resulting changes of mechanical properties and function, as determined by physical experiments on a single cilium."

In constructing the first carefully controllable example of active matter, the center will study actin filaments, which propel themselves through space by getting longer at one end and shorter at the other in a process called tread-milling polymerization.

"How do these moving filaments feel the presence of their neighbors in a large organized array? How do they behave collectively? Are there rules? It's not really clear how these organized systems of self-propelled filaments will behave, but we get hints of some possibilities from observing flocks of birds and schools of fish," said Meyer. "Understanding the rules of behavior of this new kind of matter may help us understand processes like cell motility."

The goals of the new Center include benefits for both biology and materials science. The unique position of Brandeis, in combining just the expertise and technology needed in these two fields with an atmosphere of collaboration and an eagerness to explore uncharted fields, is what won the university this prestigious award, said Meyer.

"More than just a large grant, this puts Brandeis on the world map as one of the leaders in the exciting endeavor of combining physics and chemistry with the life sciences," Meyer said. ###

Contact: Laura Gardner gardner@brandeis.edu 781-736-4204 Brandeis University

Tags: Nano or Nanotechnology and Nanotech

First 3-D processor runs at 1.4 Ghz on new architecture

Eby G. Friedman, Distinguished Professor of Electrical and Computer Engineering, Department of Electrical and Computer Engineering University of Rochester Rochester, New York 14627 USA

'Rochester Cube' points way to more powerful chip designs The next major advance in computer processors will likely be the move from today's two-dimensional chips to three-dimensional circuits, and the first three-dimensional synchronization circuitry is now running at 1.4 gigahertz at the University of Rochester. Unlike past attempts at 3-D chips, the Rochester chip is not simply a number of regular processors stacked on top of one another. It was designed and built specifically to optimize all key processing functions vertically, through multiple layers of processors, the same way ordinary chips optimize functions horizontally. The design means tasks such as synchronicity, power distribution, and long-distance signaling are all fully functioning in three dimensions for the first time.

"I call it a cube now, because it's not just a chip anymore," says Eby Friedman, Distinguished Professor of Electrical and Computer Engineering at Rochester and faculty director of the pro of the processor. "This is the way computing is going to have to be done in the future. When the chips are flush against each other, they can do things you could never do with a regular 2-D chip."

Friedman, working with engineering student Vasilis Pavlidis, says that many in the integrated circuit industry are talking about the limits of miniaturization, a point at which it will be impossible to pack more chips next to each other and thus limit the capabilities of future processors'. He says a number of integrated circuit designers anticipate someday expanding into the third dimension, stacking transistors on top of each other.

But with vertical expansion will come a host of difficulties, and Friedman says the key is to design a 3-D chip where all the layers interact like a single system. Friedman says getting all three levels of the 3-D chip to act in harmony is like trying to devise a traffic control system for the entire United States—and then layering two more United States above the first and somehow getting every bit of traffic from any point on any level to its destination on any other level—while simultaneously coordinating the traffic of millions of other drivers.

Complicate that by changing the two United States layers to something like China and India where the driving laws and roads are quite different, and the complexity and challenge of designing a single control system to work in any chip begins to become apparent, says Friedman.

Since each layer could be a different processor with a different function, such as converting MP3 files to audio or detecting light for a digital camera, Friedman says that the 3-D chip is essentially an entire circuit board folded up into a tiny package. He says the chips inside something like an iPod could be compacted to a tenth their current size with ten times the speed.

What makes it all possible is the architecture Friedman and his students designed, which uses many of the tricks of regular processors, but also accounts for different impedances that might occur from chip to chip, different operating speeds, and different power requirements. The fabrication of the chip is unique as well. Manufactured at MIT, the chip must have millions of holes drilled into the insulation that separates the layers in order to allow for the myriad vertical connections between transistors in different layers. ###

About the University of Rochester: The University of Rochester (www.rochester.edu) is one of the nation's leading private universities. Located in Rochester, N.Y., the University gives students exceptional opportunities for interdisciplinary study and close collaboration with faculty through its unique cluster-based curriculum. Its College of Arts, Sciences, and Engineering is complemented by the Eastman School of Music, Simon School of Business, Warner School of Education, Laboratory for Laser Energetics, Schools of Medicine and Nursing, and the Memorial Art Gallery.

Contact: Jonathan Sherwood jonathan.sherwood@rochester.edu 585-273-4726 University of Rochester

Old and new therapies combine to tackle atherosclerosis

Image from What is Atherosclerosis, courtesy of National Heart, Lung, and Blood Institute. Atherosclerosis in an artery (B

Futuristic nanotechnology has been teamed with a decades-old drug to beat atherosclerotic plaques in research conducted at Washington University School of Medicine in St. Louis. The scientists have found that drug-laced nanoparticles plus a statin could stop the growth of tiny blood vessels that feed arterial plaques. Their results suggest that the dual treatment also prevents the vessels from restarting their growth, which could shrink or stabilize plaques. Although the data were obtained in tests on rabbits, they raise hope that a similar approach could help human patients with atherosclerosis.

The nanoparticles — minute spheres about 20,000 times smaller than the diameter of a straight pin — were coated with a substance that made them stick in growing blood vessels and with fumagillin, a potent compound that stops blood vessel growth.

"We saw that statins sustain the acute inhibition of blood vessel growth produced by the fumagillin nanoparticles within the plaque," says senior author Gregory Lanza, M.D., Ph.D., a Washington University cardiologist at Barnes Jewish Hospital.

Lanza and co-senior author Samuel A. Wickline, M.D., published these results in the September issue of the Journal of the American College of Cardiology: Cardiovascular Imaging. Patrick M. Winter, Ph.D., research assistant professor of medicine, was the lead author of the study. Lanza is professor of medicine and biomedical engineering. Wickline is professor of medicine, physics, biomedical engineering and cell biology and physiology.

Patients with atherosclerosis often take statins to lower cholesterol. Statins also decrease atherosclerotic plaque progression by modestly inhibiting proliferation of new vessels (neovessels) within plaques. These neovessels provide increased blood and oxygen to cells in actively developing plaques. Because of their high fragility, neovessels often rupture, leading to local hemorrhages that greatly accelerate the disease process. Fumagillin nanoparticles could be used to further inhibit the development of new vessel treatment in high-risk patients, Lanza says.

"Our past research showed that fumagillin nanoparticles reduced blood vessel formation at the site of arterial plaques in experimental rabbits after one week," says Lanza. "In this study, we tested how long that effect lasts and if it could be extended by statins."

The rabbits used in the study ate a high-fat diet that caused arterial plaques. The researchers detected new blood vessel buildup at the site of plaques by coating nanoparticles that were targeted to neovessels with an MRI contrast agent.

When the rabbits received a single dose of blood-vessel-targeted nanoparticles that also carried fumagillin, the researchers saw that the amount of MRI signal at the sites of plaques decreased about five-fold by the end of one week. But a high MRI signal returned by the fourth week, indicating that plaques were active again.

Because repeated injections of fumagillin nanoparticles is impractical for treating human patients, the researchers looked for a way to extend the initial effectiveness.

Atherosclerotic rabbits that got daily doses of the statin atorvastatin (brand name Lipotor) had no change in plaque angiogenesis measured by MRI. When the statin and the fumagillin nanoparticles were started at the same time, the atorvastatin had no additional benefits over the targeted therapy.

However, when the statin had been given for at least one month prior to the fumagillin treatment, the five-fold reduction in MRI signal due to diminished neovessels was maintained for four weeks.

Lanza says that the results suggest that one or possibly two injections of nanoparticles in patients who are already on statins could lead to a long-term reduction in plaque activity and prolonged plaque stability. The results also illustrate the potential clinical use of MRI molecular imaging with the neovessel-targeted nanoparticles to measure plaque status in high-risk patients before clinical symptoms appear.

The nanoparticle technology permits potent therapeutics to be effective at minute doses by targeting them directly to the disease site. Moreover, the MRI molecular imaging with the nanoparticles could be used to noninvasively monitor and manage the response to treatment and the progression of atherosclerotic disease.

"Because nearly half of patients experiencing their first heart attack die soon after, our goal is to prevent or greatly delay clinically significant atherosclerotic disease," Lanza says. "We hope to achieve this by a personalized nanomedicine approach that risk-stratifies patients and affords safe, targeted delivery of potent compounds that block progression in high-risk patients. This would be followed by management of the disease with standard-of-care drugs and periodic MRI monitoring of disease progression. We plan to conduct clinical trials to test this idea."

###

Winter PM, Caruthers SD, Williams TA, Wickline SA, Lanza GM. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. Journal of the American College of Cardiology: Cardiovascular Imaging, Sept. 15, 2008.

Funding from the National Cancer Institute, the National Hearth Lung and Blood Institute, the National Institute for Biomedical Imaging and Bioengineering, Philips Medical Systems and Philips Research supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Contact: Gwen Ericson ericsong@wustl.edu 314-286-0141 Washington University School of Medicine

Tags: Nano or Nanotechnology and Nanotech

Researchers develop nano-sized 'cargo ships' to target and destroy tumors VIDEO

Scientists have developed nanometer-sized 'cargo ships' that can sail throughout the body via the bloodstream without immediate detection from the body's immune radar system and ferry their cargo of anti-cancer drugs and markers into tumors that might otherwise go untreated or undetected.

In a forthcoming issue of the Germany-based chemistry journal Angewandte Chemie, scientists at UC San Diego, UC Santa Barbara and MIT report that their nano-cargo-ship system integrates therapeutic and diagnostic functions into a single device that avoids rapid removal by the body's natural immune system.

"The idea involves encapsulating imaging agents and drugs into a protective 'mother ship' that evades the natural processes that normally would remove these payloads if they were unprotected," said Michael Sailor, a professor of chemistry and biochemistry at UCSD who headed the team of chemists, biologists and engineers that turned the fanciful concept into reality. "These mother ships are only 50 nanometers in diameter, or 1,000 times smaller than the diameter of a human hair, and are equipped with an array of molecules on their surfaces that enable them to find and penetrate tumor cells in the body." These microscopic cargo ships could one day provide the means to more effectively deliver toxic anti-cancer drugs to tumors in high concentrations without negatively impacting other parts of the body.

Caption: UCSD graduate student Ji-Ho Park holds a vial containing the nanometer-sized cargo ships, composed of a magnetic nanoparticle, a fluorescent quantum dot and an anti-cancer drug molecule that will be left on the site of the tumor. Credit: Luo Gu, UCSD. Usage Restrictions: None.

"Many drugs look promising in the laboratory, but fail in humans because they do not reach the diseased tissue in time or at concentrations high enough to be effective," said Sangeeta Bhatia, a physician, bioengineer and professor of Health Sciences and Technology at MIT who played a key role in the development. "These drugs don't have the capability to avoid the body's natural defenses or to discriminate their intended targets from healthy tissues. In addition, we lack the tools to detect diseases such as cancer at the earliest stages of development, when therapies can be most effective."

Caption: The nanometer-sized cargo ships look individually like a chocolate-covered nut cluster, in which a biocompatible lipid forms the chocolate shell and magnetic nanoparticles, quantum dots and the drug doxorubicin are the nuts. Credit: Ji-Ho Park, UCSD. Usage Restrictions: None.

The researchers designed the hull of the ships to evade detection by constructing them of specially modified lipids--a primary component of the surface of natural cells. The lipids were modified in such a way as to enable them to circulate in the bloodstream for many hours before being eliminated. This was demonstrated by the researchers in a series of experiments with mice. The researchers also designed the material of the hull to be strong enough to prevent accidental release of its cargo while circulating through the bloodstream.

Tethered to the surface of the hull is a protein called F3, a molecule that sticks to cancer cells. Prepared in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara, F3 was engineered to specifically home in on tumor cell surfaces and then transport itself into their nuclei.

"We are now constructing the next generation of smart tumor-targeting nanodevices," said Ruoslahti. "We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors."

The researchers loaded their ships with three payloads before injecting them in the mice. Two types of nanoparticles, superparamagnetic iron oxide and fluorescent quantum dots, were placed in the ship's cargo hold, along with the anti-cancer drug doxorubicin. The iron oxide nanoparticles allow the ships to show up in a Magnetic Resonance Imaging, or MRI, scan, while the quantum dots can be seen with another type of imaging tool, a fluorescence scanner.

"The fluorescence image provides higher resolution than MRI," said Sailor. "One can imagine a surgeon identifying the specific location of a tumor in the body before surgery with an MRI scan, then using fluorescence imaging to find and remove all parts of the tumor during the operation."

The team found to its surprise in its experiments that a single mother-ship can carry multiple iron oxide nanoparticles, which increases their brightness in the MRI image.

"The ability of these nanostructures to carry more than one superparamagnetic nanoparticle makes them easier to see by MRI, which should translate to earlier detection of smaller tumors," said Sailor. "The fact that the ships can carry very dissimilar payloads—a magnetic nanoparticle, a fluorescent quantum dot, and a small molecule drug—was a real surprise."

The researchers noted that the construction of so-called "hybrid nanosystems" that contain multiple different types of nanoparticles is being explored by several other research groups. While hybrids have been used for various laboratory applications outside of living systems, said Sailor, there are limited studies done in vivo, or within live organisms, particularly for cancer imaging and therapy.

"That's because of the poor stability and short circulation times within the blood generally observed for these more complicated nanostructures," he added. As a result, the latest study is unique in one important way.

"This study provides the first example of a single nanomaterial used for simultaneous drug delivery and multimode imaging of diseased tissue in a live animal," said Ji-Ho Park, a graduate student in Sailor's laboratory who was part of the team. Geoffrey von Maltzahn, a graduate student working in Bhatia's laboratory, was also involved in the project, which was financed by a grant from the National Cancer Institute of the National Institutes of Health.

The nano mother ships look individually like a chocolate-covered nut cluster, in which a biocompatible lipid forms the chocolate shell and magnetic nanoparticles, quantum dots and the drug doxorubicin are the nuts. They sail through the bloodstream in groups that, under the electron microscope, look like small, broken strands of pearls.

The researchers are now working on developing ways to chemically treat the exteriors of the nano ships with specific chemical "zip codes," that will allow them to be delivered to specific tumors, organs and other sites in the body. ###

Contact: Kim McDonald kimmcdonald@ucsd.edu 858-534-7572 University of California - San Diego

Tags: Nano or Nanotechnology and Nanotech