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Nanomedicine lab registry ranks the nanolabs

George Elvin

Ever wonder who the world's leaders are when it comes to nanomedicine research? Well now you can find the answer at the new nanomedicine lab registry from Nanomedicine and Nanobiology Research.

The registry ranks the top 382 laboratories based on medline abstracts, with labs ranked according to the citation rate of each individual article.

Here are the top five:

Chad Mirkin: Department of Chemistry and Institute for Nanotechnology, Northwestern University
Pat Couvreur: UMR CNRS 8612 Physico-chimie, Pharmacotechnie, Biopharmacie-Universite de Paris-Sud
Royce Murray: Kenan Laboratories of Chemistry, University of North Carolina, Chapel Hill
Dave Reinhoudt: Laboratory of Supramolecular Chemistry and Technology, MESA+ Institute for Nanotechnology, University of Twente
Ralph Weissleder: Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston

The registry, like Nanomedicine and Nanobiology Research, is run by Ion Channel Media Group. Ion founder and CEO J. Christian Hesketh, M.Sc., told me the registry is intended to help new graduate students and postdocs to find high impact laboratories. He thinks it may also interest the general public if they are interested in the most productive labs.

It looks like a great resource. I also find it interesting that labs names are listed after the names of their leaders, and three times smaller. Is the cult of personality that predominant in the world of nanomedicine labs?

Nanoscale Copies: Parallel method makes 55,000 copies of minuscule pattern in minutes

Mitch Jacoby, Chemical & Engineering News

Scanning probes are often characterized as powerful tools for building nanostructures but limited to making those structures one at a time. The perceived limitation may soon be a thing of the past.

Printing Money 80-nm-wide features in the face of Thomas Jefferson that appears on a 2005 U.S. nickel are drawn by a new dip-pen method that can make 55,000 copies of the pattern in minutes.

Researchers at Northwestern University have demonstrated that 55,000 copies of a complex nanoscale pattern can be drawn simultaneously in just minutes (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200603142). The square-centimeter-sized array of patterns is generated in a dot matrix fashion using a dip-pen nanolithography (DPN) method that transfers a molecular ink to a solid surface via microscopic cantilever tips.

Over the years, countless experts have observed that although scanning tunneling microscopes (STM) and atomic force microscopes (AFM) are uniquely able to probe and manipulate matter on the atomic scale, the one-at-a-time production rate precludes their use in large-scale fabrication of nanostructures.

"Since the inception of STM and AFM, researchers have talked about using such tools to develop new types of molecule-based nanofabrication processes," says Chad A. Mirkin, a professor of chemistry and materials science who led the study. "But development of such techniques has hit a brick wall: throughput."

To overcome some of the commonly encountered problems, Mirkin's research group designed a tiny chip that features 55,000 custom-made cantilevers and developed a simple procedure that prepares the array for use in a commercial DPN instrument.

A combination of unique features makes the array a simple and robust patterning tool, Mirkin explains. To begin with, the cantilevers are slightly curved, and the tips are unusually tall. These features provide both clearance between the cantilever and the surface that will be patterned and increased tolerance of variations in surface morphology. In addition, the tips are aligned via a gravity-driven procedure, making the new wire-free design much simpler than wired multitip tools designed by other research groups, Mirkin says.

Demonstrating the new tool's abilities, Mirkin, postdoc Yuhuang Wang, and their coworkers formed 55,000 copies of a 2005 nickel coin from a pattern of 80-nm dots of 1-octadecanethiol (about 9,000 dots per nickel) in less than 30 minutes.

The method provides "a new way of generating nanostructures on a macroscopic scale," says Harald Fuchs, a physics professor at the University of Munster, in Germany.

Noting that the technique has been used with phospholipids and other types of "inks," Fuchs points to the possibilities of combinatorial methods and remarks that there is "fantastic potential for further developments in biochemical and physical-chemical applications."

Northwestern Receives Major Award For Nanotechnology Cancer Center

Megan Fellman, University Relations, Northwestern University

EVANSTON, Ill. --- Northwestern University has been awarded a significant five-year grant from the National Cancer Institute (NCI) to establish a Center for Cancer Nanotechnology Excellence (CCNE). The new center will develop innovative nanotechnology approaches and devices to combat cancer.

The center at Northwestern is one of seven CCNEs established across the country. These centers are a major component of NCI’s $144.3 million five-year initiative for nanotechnology in cancer research. First-year funding for Northwestern is $3.9 million. "Funding for the following four years has not yet been determined, but is expected at approximately the same level," said Chad A. Mirkin, who will direct the new center.

"This is a truly exciting opportunity,"said Mirkin, George B. Rathmann Professor of Chemistry, professor of medicine and professor of materials science and engineering. "We look forward to establishing this center and working for years to come on the important problems of cancer diagnostics and therapeutics."

Capitalizing on the existing partnership between the University's International Institute for Nanotechnology (IIN) and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, the center will support multidisciplinary teams of nano-scientists, cancer biologists, engineers and clinicians who will work collaboratively to develop nanomaterials and nanodevices for cancer therapeutics, drug delivery, imaging, diagnostics and monitoring applications.

"This new center will bring together two of Northwestern's strongest research entities with the shared goal of using advances in nanoscience and technology to address one of the world’s most deadly and debilitating classes of diseases,"said Mirkin, director of the IIN. "It is possible that nanotechnology will become one of the fundamental drivers in oncology and cancer research, and we are extremely excited about focusing our research in this direction."

The new center will build upon and leverage previous research advancements and discoveries. For example, significant advances at Northwestern in the development of highly sensitive and selective nanoscale sensors will provide a research foundation for the early detection of ovarian cancer. Although the cure rate for ovarian cancer is high if detected early, ovarian cancer is the leading cause of death from gynecologic cancers. Using nanotechnology, researchers hope to provide a screening tool that identifies patients in early stages of ovarian cancer, when treatments are most effective.

Center researchers also will combine advanced research in molecular and cell biology with nanotechnology with the goal of developing a new class of drugs that inhibit cancer cells from spreading throughout the body. Other projects include developing imaging probes hundreds of times more sensitive than those currently available and with the ability to report on physiological changes in cells and developing nanoscale cargo bins that can target cancer cells, bind to them and unload chemotherapeutic agents directly to the source.

"This new effort will build a bridge between scientists, engineers and clinicians -- all focused on advancing the application of nanotechnology for the diagnosis, early detection and treatment of human cancer,"said Steven T. Rosen, M.D., director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and Genevieve Teuton Professor of Medicine at the Feinberg School of Medicine. "I am confident that this effort will lead to new discoveries that will enhance the care of patients and lead to approaches that prolong life."

The center will be able to leverage existing infrastructure as well as an extensive array of equipment, facilities and laboratories. On the Evanston campus, center researchers are housed in the four-story, 44,000 net square-foot, state-of-the-art Center for Nanofabrication and Molecular Self-Assembly, which opened in 2002; the O.T. Hogan Biological Sciences Building; the Technological Institute; and the Arthur and Gladys Pancoe-Evanston Northwestern Healthcare Life Sciences Pavilion. On the Chicago campus, center researchers will be housed in the Montgomery Ward Memorial Building and the 12-story, 220,000 net square-foot Robert H. Lurie Medical Research Center, which opened in April 2005.

Additionally, researchers will be able to utilize a wealth of instrumentation at 16 existing shared facilities including the recently established Nanoscale Imaging, Fabrication, Testing and Instrumentation (NIFTI) Facility on the Evanston campus and the Bioinformatics Core and Biostatistics Core facilities on the Chicago campus.

The center will provide an array of educational and training programs to a diverse constituency. Speakers at seminars and symposia will disseminate research progress and results to the clinical oncology community and build effective bridges of communications between practitioners and researchers. A research program in ethical and social implications of nanotechnology in translational research will be launched, engaging center researchers with philosophers, social scientists, public policy makers and the public. Graduate students and postdoctoral fellows will be involved in center research at all levels, and curriculum enhancements are expected to reflect this new initiative.

Eighteen companies have expressed formal interest in partnering with the center to help transition new technologies into the private sector. Academic collaborators include the University of Chicago, the University of Illinois at Urbana-Champaign and Yonsei University in South Korea.

Key leadership of the new center will be provided by Mirkin as director; Rosen as a member of the executive committee; Jill Pelling, professor of pathology and associate director for translational research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, as associate director; and Kathleen Cook, director of operations and marketing of the IIN, as director of operations. All were instrumental in the development of this new initiative.

The International Institute for Nanotechnology, a collaboration between Northwestern University and the Center for Nanoscale Materials at Argonne National Laboratory, is an umbrella organization which unites more than $275 million in nanotechnology research, educational programs and infrastructure under one umbrella.

The Robert H. Lurie Comprehensive Cancer Center of Northwestern University is an NCI-designated, comprehensive cancer center conducting a broad range of multidisciplinary basic, clinical and population science research with more than $116 million dollars in annual extramural funding.

A Giant Step Toward Tiny Functional Nanowires

Megan Fellman, University Relations, Northwestern University

EVANSTON, Ill. --- Carving a telephone pole is easy if you have the right tools, say a power saw and some large chisels. And with some much tinier tools you could even carve a design into a paper clip if you wanted to. But shrink your sights down to the nanoscale, to a nanowire that is 1,000 times smaller than the diameter of a paper clip, and you find there are no physical tools to do the job properly.

So a team of Northwestern University scientists turned to chemistry and developed a new method that can routinely and cheaply produce nanowires with gaps as small as five nanometers wide -- a feat that is unattainable using conventional lithographic techniques. The results will be published in the July 1 issue of the journal Science.

Carved gaps are essential to a nanowire's function, and controlling those gaps would allow scientists and engineers to design with precision devices ranging from tiny integrated circuits to gene chips and protein arrays for diagnostics and drug discovery.

"With miniaturization happening across so many fields, our existing tools -- our chisels of a sort -- can't control the shapes and spacing of these small structures,ˇ± said Chad A. Mirkin, director of Northwestern's Institute for Nanotechnology, who led the research team. ˇ°Our method allows us to selectively introduce gaps into the wires. These gaps can be filled with molecules, making them components for building small electronic and photonic devices or chemical and biological sensors."

The development of sophisticated nanoelectronics, said Mirkin, depends on the ability to fabricate and functionalize electrode gaps less than 20 nanometers wide for precise electrical measurements on nanomaterials and even individual molecules. While conventional techniques can't make gaps much smaller than 20 nanometers wide, Mirkin's method, called on-wire lithography, or OWL, has been able to produce gaps as small as 2.5 nanometers wide.

Mirkin and his team made the notched structures by first depositing into a porous template segmented nanowires made of two materials, one that is resistant to wet-chemical etching (gold) and one that is susceptible (nickel). The template is then dissolved, releasing the nanowires. Next, the wires are dispersed on a flat substrate, and a thin layer of glass is deposited onto their exposed faces. They are then suspended in solution, and a selective wet-chemical etching removes the nickel, leaving gold nanowires with well-defined gaps where the nickel used to be. (The glass is used as a bridging material, to hold the nanowire together.)

Using the OWL method, the researchers prepared nanowires with designed gaps of 5, 25, 40, 50, 70, 100, 140 and 210 nanometers wide. (A nanometer is one billionth of a meter or roughly the length of three atoms side by side. A DNA molecule is 2.5 nanometers wide.) In recent days, they have refined the technique to be able to make gaps as small as 2.5 nanometers wide.

"With dip-pen nanolithography, we can then drop into these gaps many different molecules, depending on what function we want the structure to have,ˇ± said Mirkin, also George B. Rathmann Professor of Chemistry. ˇ°This really opens up the possibility of using molecules as components for a variety of nanoscale devices."

In addition to Mirkin, other authors on the Science paper are Lidong Qin (lead author), Sungho Park and Ling Huang of Northwestern University. The research was supported by the National Science Foundation, the U.S. Air Force Office of Scientific Research, and the Defense Advanced Research Projects Agency.

Nanoparticles for detecting Alzheimer`s disease

Materials Today (U.K.) April 2005

A team at Northwestern University led by Chad A. Mirkin, together with the Rush University Medical Center, has used its nanoparticle-based bio-barcode amplification (BCA) assay - which is a million times more sensitive than standard enzyme-linked immunoassays (ELISAs) - in the first diagnostic test for the potential Alzheimer`s disease marker amyloid-beta-diffusible ligands (ADDLs), a 5nm wide protein found in low concentration in cerebrospinal fluid.

Coauthor William L. Klein of Northwestern`s Institute for Neuroscience suggests that ADDLs first appear in the earliest stages of Alzheimer`s. If BCA can identify them before symptoms develop, then the disease could be combated in its nascent form when treatments may be most effective. In BCA, both magnetic microparticles and 30 nm Au nanoparticles are attached to antibodies for ADDL. The nanoparticles also attach to hundreds of identical barcode DNA strands. Because of the antibodies, ADDL molecules bind to both a Au-DNA particle and a magnetic particle (forming a sandwich complex). These are then separated from the rest of the sample by a magnetic field and heated to release the DNA barcodes, which are then measured by a standard chip-based detection method. Each nanoparticles links to many barcode DNA strands, which greatly amplifies the signal from each ADDL molecule.

"The very earliest stages of Alzheimer`s disease memory loss begin when ADDLs attack key synapses in the brain. We predicted that some of these ADDLs would leak into the cerebrospinal fluid, but until now we could not detect them," says Klein. "It's been possible to validate the prediction, and maybe even set the stage for creating the first clinical lab test for Alzheimer`s disease."

In measurements in 30 individuals, the half with Alzheimer`s showed higher ADDL concentrations. Current diagnosis is only about 85% accurate. The researchers aim to develop the test for blood or urine samples, which are easier to obtain.

BCA could also be configured to detect hundreds of diseases simultaneously, and has already been used in experiments with biomarkers for AIDS and prostate cancer.

Tiny is Beautiful: Translating "Nano" into Practical

By THE ASSOCIATED PRESS

New York Times February 22, 2005

MIRKIN GROUP MEMBERS WIN COLLEGIATE INVENTORS COMPETITION FOR SECOND YEAR IN A ROW

Innovation is alive and kicking on campus

Scientific American February, 2005

The Collegiate Inventors Competition, sponsored by the National Inventors Hall of Fame awards efforts in establishing new technology as it emerges from colleges and universities throughout the US and around the world. The CIC recognizes and encourages students on their quest to change tomorrow. Mirkin Group members, C. Shad Thaxton and Jwa-Min Nan together invented a new technology with the potential to take their respective fields of medical research and chemistry to a new level for which they were awarded the Graduate Winners of the Collegiate Inventors Award - Team category.

The two researchers created what is called a "bio barcode amplified detection system." It is a complex process with a simple goal: to find miniscule amounts of microscopic biological materials. Because their invention is so much more sensitive and precise than previous types of tests, it could be used to detect chemical signs of Alzheimer's disease or types of cancer far earlier than conventional tests.

The invention stems from the recognition that tiny bits of protein control many types of bodily functions both normal and abnormal. Abnormal conditions can often be diagnosed by detecting bits of protein. Hard-to-diagnose conditions ranging from Alzheimer's to Mad Cow Disease are hard to pinpoint because there are very few proteins in blood or other biological samples, especially early on in the course of the disease. Working together in the lab at Northwestern University's Institute For Nanotechnology, Nam and Thaxton figured out a way to attach bits of iron to the specific protein molecules they seek. They also used nanosized gold particles to attach numerous bits of DNA. It was so easy to spot and identify that they nicknamed this DNA as their "bar code." By using magnets to attract the bits of iron, the inventors simply performed tests on samples and then looked for the bio barcodes.

Winners were announced Oct. 2, 2004 during a ceremony held in Akron, Ohio. Two undergraduate winners, two graduate winners and one grand prizewinner were selected from 15 finalist teams, selected earlier from 155 original entries. Nine of the finalists were graduate teams. Now in its 15th year, the Collegiate Inventors Competition is an international competition designed to encourage college students to be active in science, engineering, mathematics, technology and creative invention. This prestigious challenge recognizes and rewards the inventiveness of a new idea, process or technology, discoveries and research by college and university students, and their advisors for projects leading to inventions that can be patented.

DR. CHAD A. MIRKIN RECEIVES NIH DIRECTOR'S PIONEER AWARD 2004

In October 2004, Chad Mirkin received the NIH Director's Pioneer Award from the National Institutes of Health. Established in January 2004, the Director's Pioneer Award recognizes exceptional researchers and thinkers from multiple disciplines who have highly innovative ideas and approaches to contemporary challenges in biomedical research. Mirkin was one of only nine awardees from the approximately 1,000 nominations NIH received from around the country and the only awardee from the Midwest.

As part of the award, Mirkin received approximately $3.7 million over five years to allow him the time and resources to test far-ranging ideas with the potential to make extraordinary contributions to medical research.

Megan Fellman

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