David Kirkpatrick

August 25, 2010

Making nano-brushes even smaller

Filed under: Science — Tags: , , , , , , — David Kirkpatrick @ 11:52 am

Now this is a nanotech development that can lead to real-world applications.

From the link:

In their latest series of experiments, Duke University engineers have developed a novel approach to synthesize these nano-brushes, which could improve their versatility in the future. These polymer brushes are currently being used in biologic sensors and microscopic devices, such as microcantilevers, and they will play an important role in the future drive to miniaturization, the researchers said.

Nano-brushes are typically made of  grown on flat surfaces with strands of the molecules growing up and out from a surface, much like hairs on a brush. Polymers are large man-made molecules ubiquitous in the manufacture of everyday products.

An atomic force microscopy topographic image of the nano-brushes. The relative heights of the brushes can be tailored by changing the substrate and initiators. Credit: Stefan Zauscher, Pratt School of Engineering

May 12, 2010

DNA-based logic chips

Very cool and very fascinating in terms of extreme mass production.

The release:

DNA could be backbone of next generation logic chips

IMAGE: This is Duke University’s Chris Dwyer.

Click here for more information.

DURHAM, N.C. – In a single day, a solitary grad student at a lab bench can produce more simple logic circuits than the world’s entire output of silicon chips in a month.

So says a Duke University engineer, who believes that the next generation of these logic circuits at the heart of computers will be produced inexpensively in almost limitless quantities. The secret is that instead of silicon chips serving as the platform for electric circuits, computer engineers will take advantage of the unique properties of DNA, that double-helix carrier of all life’s information.

In his latest set of experiments, Chris Dwyer, assistant professor of electrical and computer engineering at Duke’s Pratt School of Engineering, demonstrated that by simply mixing customized snippets of DNA and other molecules, he could create literally billions of identical, tiny, waffle-looking structures.

Dwyer has shown that these nanostructures will efficiently self-assemble, and when different light-sensitive molecules are added to the mixture, the waffles exhibit unique and “programmable” properties that can be readily tapped. Using light to excite these molecules, known as chromophores, he can create simple logic gates, or switches.

These nanostructures can then be used as the building blocks for a variety of applications, ranging from the biomedical to the computational.

IMAGE: This is a closeup of a waffle.

Click here for more information.

“When light is shined on the chromophores, they absorb it, exciting the electrons,” Dwyer said. “The energy released passes to a different type of chromophore nearby that absorbs the energy and then emits light of a different wavelength. That difference means this output light can be easily differentiated from the input light, using a detector.”

Instead of conventional circuits using electrical current to rapidly switch between zeros or ones, or to yes and no, light can be used to stimulate similar responses from the DNA-based switches – and much faster.

“This is the first demonstration of such an active and rapid processing and sensing capacity at the molecular level,” Dwyer said. The results of his experiments were published online in the journal Small. “Conventional technology has reached its physical limits. The ability to cheaply produce virtually unlimited supplies of these tiny circuits seems to me to be the next logical step.”

DNA is a well-understood molecule made up of pairs of complimentary nucleotide bases that have an affinity for each other. Customized snippets of DNA can cheaply be synthesized by putting the pairs in any order. In their experiments, the researchers took advantage of DNA’s natural ability to latch onto corresponding and specific areas of other DNA snippets.

Dwyer used a jigsaw puzzle analogy to describe the process of what happens when all the waffle ingredients are mixed together in a container.

“It’s like taking pieces of a puzzle, throwing them in a box and as you shake the box, the pieces gradually find their neighbors to form the puzzle,” he said. “What we did was to take billions of these puzzle pieces, throwing them together, to form billions of copies of the same puzzle.”

IMAGE: These are many waffles.

Click here for more information.

In the current experiments, the waffle puzzle had 16 pieces, with the chromophores located atop the waffle’s ridges. More complex circuits can be created by building structures composed of many of these small components, or by building larger waffles. The possibilities are limitless, Dwyer said.

In addition to their use in computing, Dwyer said that since these nanostructures are basically sensors, many biomedical applications are possible. Tiny nanostructures could be built that could respond to different proteins that are markers for disease in a single drop of blood.

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Dwyer’s research is supported by the National Science Foundation, the Air Force Research Laboratory, the Defense Advanced Research Projects Agency and the Army Research Office. Other members of the Duke team were Constantin Pistol, Vincent Mao, Viresh Thusu and Alvin Lebeck

March 13, 2010

More gold nanotech cancer research

I’ve done a lot of blogging on cancer and nanotech and I’ve covered this exact use of gold nanoparticles to destroy tumors. This is new research on the same tech, and this amount of news on one cancer-fighting technique is good medical news. Earlier this week I covered this topic on research from Cornell. Today’s news comes from Washington University in St. Louis.

From the final link, the release:

A golden bullet for cancer

Nanoparticles provide a targeted version of photothermal therapy for cancer

IMAGE: Infrared images made while tumors were irradiated with a laser show that in nanocage-injected mice (left), the surface of the tumor quickly became hot enough to kill cells. In…

Click here for more information.

In a lecture he delivered in 1906, the German physician Paul Ehrlich coined the term Zuberkugel, or “magic bullet,” as shorthand for a highly targeted medical treatment.

Magic bullets, also called silver bullets, because of the folkloric belief that only silver bullets can kill supernatural creatures, remain the goal of drug development efforts today.

A team of scientists at Washington University in St. Louis is currently working on a magic bullet for cancer, a disease whose treatments are notoriously indiscriminate and nonspecific. But their bullets are gold rather than silver. Literally.

The gold bullets are gold nanocages that, when injected, selectively accumulate in tumors. When the tumors are later bathed in laser light, the surrounding tissue is barely warmed, but the nanocages convert light to heat, killing the malignant cells.

In an article just published in the journal Small, the team describes the successful photothermal treatment of tumors in mice.

IMAGE: The color of a suspension of nanocages depends on the thickness of the cages’ walls and the size of pores in those walls. Like their color, their ability to absorb…

Click here for more information.

The team includes Younan Xia, Ph.D., the James M. McKelvey Professor of Biomedical Engineering in the School of Engineering and Applied Science, Michael J. Welch, Ph.D., professor of radiology and developmental biology in the School of Medicine, Jingyi Chen, Ph.D., research assistant professor of biomedical engineering and Charles Glaus, Ph.D., a postdoctoral research associate in the Department of Radiology.

“We saw significant changes in tumor metabolism and histology,” says Welch, “which is remarkable given that the work was exploratory, the laser ‘dose’ had not been maximized, and the tumors were ‘passively’ rather than ‘actively’ targeted.”

Why the nanocages get hot

The nanocages themselves are harmless. “Gold salts and gold colloids have been used to treat arthritis for more than 100 years,” says Welch. “People know what gold does in the body and it’s inert, so we hope this is going to be a nontoxic approach.”

“The key to photothermal therapy,” says Xia, “is the cages’ ability to efficiently absorb light and convert it to heat. “

Suspensions of the gold nanocages, which are roughly the same size as a virus particle, are not always yellow, as one would expect, but instead can be any color in the rainbow.

They are colored by something called a surface plasmon resonance. Some of the electrons in the gold are not anchored to individual atoms but instead form a free-floating electron gas, Xia explains. Light falling on these electrons can drive them to oscillate as one. This collective oscillation, the surface plasmon, picks a particular wavelength, or color, out of the incident light, and this determines the color we see.

IMAGE: Gold nanocages (right) are hollow boxes made by precipitating gold on silver nanocubes (left). The silver simultaneously erodes from within the cube, entering solution through pores that open in the…

Click here for more information.

Medieval artisans made ruby-red stained glass by mixing gold chloride into molten glass, a process that left tiny gold particles suspended in the glass, says Xia.

The resonance — and the color — can be tuned over a wide range of wavelengths by altering the thickness of the cages’ walls. For biomedical applications, Xia’s lab tunes the cages to 800 nanometers, a wavelength that falls in a window of tissue transparency that lies between 750 and 900 nanometers, in the near-infrared part of the spectrum.

Light in this sweet spot can penetrate as deep as several inches in the body (either from the skin or the interior of the gastrointestinal tract or other organ systems).

The conversion of light to heat arises from the same physical effect as the color. The resonance has two parts. At the resonant frequency, light is typically both scattered off the cages and absorbed by them.

By controlling the cages’ size, Xia’s lab tailors them to achieve maximum absorption.

Passive targeting

“If we put bare nanoparticles into your body,” says Xia, “proteins would deposit on the particles, and they would be captured by the immune system and dragged out of the bloodstream into the liver or spleen.”

To prevent this, the lab coated the nanocages with a layer of PEG, a nontoxic chemical most people have encountered in the form of the laxatives GoLyTELY or MiraLAX. PEG resists the adsorption of proteins, in effect disguising the nanoparticles so that the immune system cannot recognize them.

Instead of being swept from the bloodstream, the disguised particles circulate long enough to accumulate in tumors.

A growing tumor must develop its own blood supply to prevent its core from being starved of oxygen and nutrients. But tumor vessels are as aberrant as tumor cells. They have irregular diameters and abnormal branching patterns, but most importantly, they have thin, leaky walls.

The cells that line a tumor’s blood vessel, normally packed so tightly they form a waterproof barrier, are disorganized and irregularly shaped, and there are gaps between them.

The nanocages infiltrate through those gaps efficiently enough that they turn the surface of the normally pinkish tumor black.

A trial run

In Welch’s lab, mice bearing tumors on both flanks were randomly divided into two groups. The mice in one group were injected with the PEG-coated nanocages and those in the other with buffer solution. Several days later the right tumor of each animal was exposed to a diode laser for 10 minutes.

The team employed several different noninvasive imaging techniques to follow the effects of the therapy. (Welch is head of the oncologic imaging research program at the Siteman Cancer Center of Washington University School of Medicine and Barnes-Jewish Hospital and has worked on imaging agents and techniques for many years.)

During irradiation, thermal images of the mice were made with an infrared camera. As is true of cells in other animals that automatically regulate their body temperature, mouse cells function optimally only if the mouse’s body temperature remains between 36.5 and 37.5 degrees Celsius (98 to 101 degrees Fahrenheit).

At temperatures above 42 degrees Celsius (107 degrees Fahrenheit) the cells begin to die as the proteins whose proper functioning maintains them begin to unfold.

In the nanocage-injected mice, the skin surface temperature increased rapidly from 32 degrees Celsius to 54 degrees C (129 degrees F).

In the buffer-injected mice, however, the surface temperature remained below 37 degrees Celsius (98.6 degrees Fahrenheit).

To see what effect this heating had on the tumors, the mice were injected with a radioactive tracer incorporated in a molecule similar to glucose, the main energy source in the body. Positron emission and computerized tomography (PET and CT) scans were used to record the concentration of the glucose lookalike in body tissues; the higher the glucose uptake, the greater the metabolic activity.

The tumors of nanocage-injected mice were significantly fainter on the PET scans than those of buffer-injected mice, indicating that many tumor cells were no longer functioning.

The tumors in the nanocage-treated mice were later found to have marked histological signs of cellular damage.

Active targeting

The scientists have just received a five-year, $2,129,873 grant from the National Cancer Institute to continue their work with photothermal therapy.

Despite their results, Xia is dissatisfied with passive targeting. Although the tumors took up enough gold nanocages to give them a black cast, only 6 percent of the injected particles accumulated at the tumor site.

Xia would like that number to be closer to 40 percent so that fewer particles would have to be injected. He plans to attach tailor-made ligands to the nanocages that recognize and lock onto receptors on the surface of the tumor cells.

In addition to designing nanocages that actively target the tumor cells, the team is considering loading the hollow particles with a cancer-fighting drug, so that the tumor would be attacked on two fronts.

But the important achievement, from the point of view of cancer patients, is that any nanocage treatment would be narrowly targeted and thus avoid the side effects patients dread.

The TV and radio character the Lone Ranger used only silver bullets, allegedly to remind himself that life was precious and not to be lightly thrown away. If he still rode today, he might consider swapping silver for gold.

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November 13, 2008

More nanoparticle caution

I’ve blogged on nanotechnology drawbacks before, and here’s a new release providing a little more caution on nanotech. Sounds like this research may be more alarmist than truly useful. Be sure to take your grain of salt here.

The release:

Nanoparticles trigger cell death?

Nanoparticles that are one milliard of a metre in size are widely used, for example, in cosmetics and food packaging materials. There are also significant amounts of nanoparticles in exhaust emissions. However, very little is yet known of their health effects, because only a very small portion of research into nanoparticles is focused on their health and safety risks. Nanoparticles have even been dubbed the asbestos of the 2000s bys some researchers, and therefore a considerable threat to people’s health. While the use of nanoparticles in consumer products increases, their follow-up procedures and legislation are lagging behind. The European Union chemicals directive REACH does not even touch upon nanomaterials.

The research teams of Professor Ilpo Vattulainen (Department of Physics, Tampere University of Technology, Finland) and academy researcher Emppu Salonen (Department of Applied Physics, Helsinki University of Technology, Finland) have together with Professor Pu-Chun Ke’s (Clemson University, SC, USA) team researched how carbon-based nanoparticles interact with cells. The results provided strong biophysical evidence that nanoparticles may alter cell structure and pose health risks.

It emerged from the research that certain cell cultures are not affected when exposed to fullerenes, i.e. nano-sized molecules that consist of spherical, ellipsoid, or cylindrical arrangement of carbon atoms. Cells are also not affected when exposed to gallic acid, an organic acid that is found in almost all plants and, for instance, in tea. However, when fullerenes and gallic acid are present in the cell culture at the same time, they interact to form structures that bind to the cell surface and cause cell death.

The research demonstrates how difficult it is to map out the health effects of nanoparticles. Even if a certain nanoparticle does not appear toxic, the interaction between this nanoparticle and other compounds in the human body may cause serious problems to cell functions. Since the number of possible combinations of nanoparticles and various biomolecules is immense, it is practically impossible to research them systematically.

 

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The research on cell death caused by fullerenes and gallic acid was recently published in the nanoscience journal Small [E. Salonen, S. Lin, M. L. Reid, M. Allegood, X. Wang, A. M. Rao, I. Vattulainen, P.-C. Ke. Real-time translocation of fullerene reveals cell contraction. Small 4, 1986-1992 (2008)].

Descriptions of group leaders and their research groups:

Professor Pu-Chun Ke:
Prof. Pu Chun Ke won a Career Award from the National Science Foundation for his research addressing the fate of nanomaterials in biological systems and the environment. His research lab has first demonstrated the delivery of RNA using single-walled carbon nanotubes and invented the use of lysophospholipids for obtaining biocompatible nanomaterials. Based at Clemson University, USA, the Single-Molecule Biophysics and Polymer Physics Laboratory led by Prof. Ke (http://people.clemson.edu/~pcke11/) also examines topics in DNA damage and repair, microscopy, and fundamental and applied soft matter physics.

Professor Ilpo Vattulainen:
The Biological Physics Group (http://www.tut.fi/biophys/ and http://www.fyslab.hut.fi/bio/) of 26 people located at the Department of Physics at Tampere University of Technology, Finland, is directed by Prof. Ilpo Vattulainen. The Group is part of the Computational Nanoscience team selected as a Center of Excellence by the Academy of Finland. The Group is also an affiliate member of the MEMPHYS Center for Biomembrane Physics in the University of Southern Denmark, selected as a Center of Excellence by The Danish National Research Foundation. The Biological Physics Group focuses on computational and theoretical studies of biological systems, the topics including biomembranes, nanomaterials, lipoproteins, drugs, and carbohydrates.

Academy researcher (Dr.) Emppu Salonen:
The Computational Soft Matter Research Group (http://www.fyslab.hut.fi/soft/) is based at the Department of Applied Physics, Helsinki University of Technology (TKK). The group is headed by Dr. Emppu Salonen, who currently has a Research Fellow position with the Academy of Finland. The focus of the group’s research is in environmental and biological effects of nanomaterials, most importantly carbon-based nanomaterials such as fullerenes and carbon nanotubes. The current nanomaterial-biomaterial research of the group is funded by the Academy of Finland.

September 28, 2008

Green gold nanotech

The release from Friday:

MU scientists go green with gold, distribute environmentally friendly nanoparticles

Mizzou scientist named as one of the 25 most influential people in radiology

COLUMBIA, Mo. — Gold nanoparticles are everywhere. They are used in cancer treatments, automobile sensors, cell phones, blood sugar monitors and hydrogen gas production. However, until recently, scientists couldn’t create the nanoparticles without producing synthetic chemicals that had negative impacts on the environment. A new method, created by a University of Missouri research team, not only eliminates any negative environmental impact, but also has resulted in national and international recognition for the lead scientist. The research was published recently in the journal Small.

“I have always believed that nature is smarter and stronger than humankind,” said Kattesh Katti, professor of radiology and physics in MU’s School of Medicine and College of Arts and Science, senior research scientist at the MU Research Reactor, and director of the MU Cancer Nanotechnology Platform. “This new procedure to create nanoparticles is wonderfully simple, yet it will help create very complex components. There is so much to learn from energy generation, chemical and photochemical reactions of plants.”

Katti, who was recently recognized by rt Image magazine as one of the 25 most influential people in radiology, and his research team have formed Greennano Company, a company that is in the beginning stages of producing environmentally friendly gold nanoparticles. The company will focus on the development, commercialization and worldwide supply of gold nanoparticles for medical and technological applications. Katti believes that because of this new process to produce the nanoparticles, researchers are developing other ways to use them.

The MU research team, which was led by Katti, Raghuraman Kannan and Kavita Katti, found that by submersing gold salts in water and then adding soybeans, gold nanoparticles were generated. The water pulls a phytochemical out of the soybean that is effective in reducing the gold to nanoparticles. A second phytochemical from the soybean, also pulled out by the water, interacts with the nanoparticles to stabilize them and keep them from fusing with the particles nearby. This process creates nanoparticles that are uniform in size in a 100-percent green process. No toxic waste is generated.

“I’m very proud to be one among the list of ’25 Most Influential Scientists’ in the world, especially in the company of all time greats and former awardees including: Elias Zerhouni, director of National Institutes of Health (2003); Henry N. Wagner Jr., recognized as the Father of Nuclear Medicine (2004); Henry D. Royal, Peter S. Conti, past presidents of the Society of Nuclear Medicine; and Barry B. Goldberg, pioneer of ultrasound (2007),” Katti said. “This recognition is a tremendous honor and brings a large amount of prestige to our research group, the Departments of Radiology and Physics, the MU Research Reactor Center and the overall research and education enterprise of our University.”

“They all had one thing in common; they possessed the integrity, drive and passion deserving of the title ‘Most Influential,’” said Heather B. Koitzsch, publisher of rt Image. “In this year’s list, you’ll read about people who are changing the face of medicine, associations that are advocating for better patient care, and researchers whose efforts are uncovering new diagnostic techniques. Whether through speaking, campaigning, researching, creating or leading, someone who is “Most Influential” is committed to making things happen in radiology.”

 

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Katti’s research has been funded by the National Cancer Institute in the National Institutes of Health.

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