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Plasmon resonance in gold nanoparticles results from the excitation of plasmons by light. Changes in molecules adsorbed onto the catalyst nanoparticles, including changes in color, are sensed by the gold nanoparticles. (Image courtesy of Elin Larsson.)

Researchers at Chalmers University of Technology (Göteborg, Sweden) have developed a measurement technology that makes use of the optical resonances in nanoparticles. Opening up new possibilities in the field of catalytics, the method will enable scientists to study catalysts in real time under realistic conditions, enhancing knowledge of catalytic processes and helping develop new catalysts. The novel sensors could potentially be used in a variety of applications, including medical diagnostics.

Optical resonances in nanoparticles, known as plasmon resonances, have been the object of intense research. Scientists are working on using the technique to detect biological molecules. The Chalmers researchers have shown that plasmon resonances in nanoparticles can be used to monitor reactions on catalysts and could lead to the design of hypersensitive sensors.

The nanoparticle research will be described in detail in the November issue of Science. Additional information is also available from Chalmers University of Technology and Physics World.

Measurement company Agilent Technologies (Santa Clara, CA) has announced that it will collaborate with researchers at Stanford University (Stanford, CA) in a research program aimed at advancing rapid prototyping and characterization of nanoscale devices. The research will focus on combining atomic layer deposition (ALD) techniques with scanning probe microscopy (SPM).

The Rapid Prototyping Lab at Stanford will work with Agilent to integrate ALD, a thin-film deposition technique, with the nanometer lateral resolution possible with SPM. By doing so, the collaborators hope to achieve feature resolution of less than 10 nm. This capability, according to the researchers, would be a breakthrough in the field because current manufacturing methods, such as optical and E-beam lithography, have failed to achieve feature resolution significantly less than 20 nm. Successful integration of the two methods could potentially open doors for the prototyping and fabrication of electronic nanoscale devices.

“The novel nanostructures will be fabricated and characterized in-situ in this unique SPM-ALD tool in order to rapidly prototype a wide variety of next-generation devices,” says Fritz Prinz, professor and chairman, mechanical engineering, Stanford University. “The SPM-ALD tool will enable us to build devices, which take advantage of the quantum-confinement effects present at small length scales, length scales that could not be accessed with traditional lithography methods. These devices can only be built with manufacturing tools possessing extraordinary spatial resolution.”

Nanoparticles (shown in pink) developed by BIND Biosciences accumulate in a prostate-cancer cell. (Photo by BIND Biosciences.)

Scientists at BIND Biosciences (Cambridge, MA) have shown that biodegradable polymer–based nanoparticles infused with drugs and encased in cancer-targeting proteins can impede the growth of prostate, breast, and lung tumors in rodents. Capable of remaining in the bloodstream for more than a day, the nanoparticle technology increases the likelihood that cancer-fighting drugs will reach their targets. The company hopes that the system will diminish the side effects of chemotherapy while killing tumors.

Some drugs on the market and in development use lipid-based nanoparticles and other technologies to extend the lifespan of cancer-fighting drugs in the bloodstream, allowing more medication to reach the target tissue through the blood vessels. But none of these formulations can target specific cells, and none enjoy extended circulation time. In addition, in most targeted nanotechnologies, the core particle is made first and later coated with the targeting molecule, a complex process offering limited repeatability.

As reported in Technology Review, published by the Massachusetts Institute of Technology (MIT; Cambridge, MA), BIND’s approach is based on the self-assembling biodegradable polymers polylactic acid and copolylactic acid/glycolic acid, which hold the desired drug in a molecular mesh, enabling it to diffuse slowly. Developed in the lab of Robert Langer, a professor of chemical engineering at MIT, the nanoparticles contain an outer layer that is made of polyethylene glycol, a molecule with water-like properties that lets the nanoparticle evade detection by proteins and the white blood cells that destroy pathogens in the blood. That stealth coating is also dotted with specially designed peptides, which bind to cells of interest.

When the three components are mixed together, structured nanoparticles form spontaneously. “Because the self assembly doesn’t require multiple complicated chemical steps, the particles are very easy to manufacture,” explains Omid Farokhzad, a scientist and physician at Harvard Medical School (Boston) and cofounder of BIND with Langer in 2006. “And we can make them on a kilogram scale, which no one else has done.”

A Hyper-SAGE image of xenon dissolved in water flowing through a phantom lung shows the intensity of an MRI signal 23 seconds into the process. The warm colors represent a stronger signal than the cool colors. (Image courtesy of Xin Zhou.)

A team of researchers at the Lawrence Berkeley National Laboratory (Berkeley, CA) are working to improve the resolution of magnetic resonance imaging (MRI) systems. Known as hyperpolarized xenon signal amplification by gas extraction (Hyper-SAGE), the scientists’ new technique uses xenon gas that has been treated with laser light to hyperpolarize the atomic nuclei, aligning the spins of the majority of its atomic nuclei. The researchers think that by dramatically boosting MRI sensitivity, the technology could enable doctors to detect ultralow concentrations of diseases such as lung cancer.

Led by MRI technology specialist Alexander Pines, a chemist at the Berkeley Lab and the University of California, Berkeley, the team has high hopes for its innovative approach. “By detecting the MRI signal of dissolved hyperpolarized xenon after the xenon has been extracted back into the gas phase, we can boost the signal’s strength up to 10,000 times,” Pines explains. “It is absolutely amazing because we’re looking at pure gas and can reconstruct the whole image of our target. With this degree of sensitivity, Hyper-SAGE becomes a highly promising tool for in vivo diagnostics and molecular imaging.”

Although widely used for medical imaging applications, MRI has been limited by sensitivity issues, especially in such areas as biomedical sampling. For the past three decades, Pines has led efforts to enhance the sensitivity of MRI and nuclear magnetic resonance (NMR) spectroscopy. Hyper-SAGE represents a significant advance for both technologies, remarks Xin Zhou, a member of Pines’s research group.

The team has developed a variety of ways to increase the sensitivity of MRI technology and expand its applicability. Previous work has shown that xenon, an inert gas whose nuclei naturally feature a tiny degree of spin polarization, can be hyperpolarized with laser light to produce a population of xenon atoms in which nearly five out of every 10 nuclei—instead of one out of every 100,000—produce an MRI signal. The team has also shown that xenon can be incorporated into a biosensor and linked to specific proteins or other biological molecules to produce spatial images of a chosen molecular or cellular target.

“Xenon gas has an intrinsically long relaxation time, greater than 45 minutes, which means the signal lasts long enough for us to collect all the encoded information, which in turn can enable us to detect specific targets, such as cancer-related proteins, at micromolar or parts per million concentrations,” Zhou says. “Also, Hyper-SAGE utilizes remote detection, meaning the signal encoding and detection processes are physically separated and carried out independently. This is a plus for imaging the lung, for example, where the signal of interest would occupy only a small portion of the traditional MRI signal receiver.”

In a paper published in Proceedings of the National Academy of Sciences titled “Hyperpolarized Xenon NMR and MRI Signal Amplification by Gas Extraction,” Zhou, Pines, and coauthor Dominic Grazianitheir describe the successful testing of the Hyper-SAGE technique on a pair of membranes that mimicked the function of the lungs. Hyperpolarized xenon was dissolved in solution in one membrane to mimic inhalation and was then extracted as a gas for detection from the other membrane to represent exhalation.

“In a clinical setting, a patient would inhale the hyperpolarized xenon gas which would be dissolved in the blood and allowed to flow into the body and brain,” Zhou says. “The exhaled xenon gas would then be collected and its MRI signal would be detected. Used in combination with a target-specific xenon biomolecular sensor, we should be able to study the gas-exchange in the lung and detect cancerous cells at their earliest stage of development.”

More information on the research is available from the Lawrence Berkeley National Laboratory.

Nanowires are at the center of a plethora of research projects occurring in an array of university labs. But a breakthrough by Harvard scientists could broaden the potential of nanowires for biosensing applications—and it has the self-assembling structures all bent out of shape.

Harvard chemistry researchers have figured out how to introduce fixed 120-degree joints, dubbed “stereocenters,” into straight nanowires. By transforming the 1-D structures into complex 2- and 3-D shapes, the scientists believe that enhanced methods of intra and extracellular electrical recording could be made possible.

Controlling nanowire structure has proven difficult in the past because the materials are self-assembling. The Harvard researchers were able to circumvent this obstacle, however, by interrupting the growth process. “The researchers halted growth of the 1-D nanostructures for 15 seconds by removing key gaseous reactants from the chemical brew in which the process was taking place, replacing these reactants after joints had been introduced into the nanostructures. This approach resulted in a 40 percent yield of bent nanowires, which can then be purified to achieve higher yields,” according to a recent article in HarvardScience.

Appearing as kinks in the no-longer-linear nanowire structure, the stereocenters, hypothesize the researchers, pave the way for the introduction of self-labeled nanodevices exhibiting some sort of functionaliity at the designated nanoscale points.

New Scientist reports that a team of French researchers from the Claude Bernard University (Lyon, France) has developed a “print ‘n shrink” technology that offers increased flexibility in the fabrication of microfluidic devices.

Current fabrication methods can limit design freedom, according to Christophe Marquette. a biochemical engineer involved in the project. The team also identified associated costs and difficulty level as additional drawbacks to established techniques. In an attempt to resolve these issues, the French scientists opted to diverge from traditional approaches. Instead, rather than trying to precisely etch the channels onto a substrate at the targeted diminutive size, the team experimented with shrinking the chip.

In their studies, the scientists were able to apply the desired microfluidic channels and patterns onto a 230-µm-square chip made from the heat-shrinkable polymer PolyShrink. Warming the PolyShrink chip prompted it to minimize in size; in turn, the thickness increased. Ultimately, the team was able to shrink the chip to 100 µm square while achieving a thickness increase from 15 to 85 µm. Because the features and channels maintained their dimensions throughout the process, the researchers believe that this method could provide more flexibility and potentially cut costs for manufacturers of microfluidic devices.

Read about another innovative approach to microfluidic device manufacturing by a savvy student from the most-recent issue of MPMN.

An ultrasonic catheter-cutting machine from Rainbow Medical Engineering incorporates a vacuum system that collects waste material, preventing chads that can endanger patient safety.

In standard catheter-cutting operations, the waste material, or chad, may not completely detach from the tube, or it may detach but remain lodged within the catheter. If not detected during the manufacturing process, the chad can migrate into the patient.

Addressing this issue, Rainbow Medical Engineering Ltd. (Letchworth Garden City, UK) has developed an ultrasonic catheter-cutting machine that incorporates a vacuum system for preventing chads from endangering patient safety. At the same time, the unit produces burr-free tubing edges. As a result of its breakthrough capability, the system has been crowned the Best Technology Application at the 2009 Plastics Industry Awards in London.

Adopted by several manufacturers in Europe and the Asia/Pacific region, the technology uses a vacuum to collect chads, which are passed through an electronic counter. If an anomaly is detected, processing is halted automatically. The production cycle cannot be restarted until the faulty catheter has been physically removed.

Data cited by Rainbow Medical show that 44% of hospital patients with an indwelling urinary catheter develop bacterial infections within 72 hours of catheterization. Infections occur in the tissue damaged by the catheter or can result from bacterial encrustation caused by burrs on the edges of the catheter apertures. Rainbow Medical’s ultrasonic cutting system produces measurably smoother, burr-free edges on the apertures than conventional systems, according to the company.

While prosthetic limbs have come a long way over the years, they still have a long way to go. Improvements in aesthetics and functionality have contributed to better end products; however, the ability for amputees to exercise neurological control over their artificial limb persists as the impossible dream. Studies recently conducted by the American Society of Plastic Surgeons (ASPS) involving the electrically conductive polymer PEDOT, however, indicate that such ambitious goals may be attainable.

Surgeons at the ASPS Plastic Surgery 2009 conference last week shared their research, which demonstrated promise for providing patients with prosthetic limbs the ability to feel heat, cold, and touch. Results of the two studies suggest that PEDOT could be the key to stimulating and growing nerve fibers. In turn, patients could some day potentially move fingers independently, experience sensation, and apply enough pressure for improved lifting and grabbing, according to the surgeons.

Nerve regeneration in a rat was achieved in one study by placing PEDOT in a tube with several additional biological and synthetic materials and grafting it to the specimen’s severed leg nerve. As a result, new nerve fibers sprouted up and compensated for the nonfunctional ones. The second study centered on using PEDOT to generate an electrical charge to enable sensation. After attaching a cup filled with cells and muscles around the severed leg nerve of a rat, the surgeons ensconced the cells and muscle in PEDOT. According to the researchers, new blood vessels, muscle, and nerve fibers formed after 114 days. Furthermore, the surgeons detected electrical signals after tickling the rat’s paw—an indication that sensation had returned.

Read more about PEDOT’s prominent role in potential medical products, especially in future electrodes.

As companies and universities invest an increasing amount of R&D hours and dollars in nanotechnology, speculation about the safety of the burgeoning technology for biomedical use has similarly been on the rise. In an effort to gain clearer insight as to how nanoparticles interact with the body, a team of Swedish scientists conducted experiments on rats to evaluate the effects of injected nanowires on their brains. Observing that there were only minor differences between the brains of the test and control groups after 12 weeks, the team has concluded that the development of nanoscale electrodes could be a biocompatible and viable option for future neurological applications.

The development of safe nanoscale electrodes could enable the advancement of neurological devices designed for the treatment of Parkinson’s disease and chronic pain, for example.  Researchers believe that such tiny electrodes could register and stimulate the most-minute parts of the brain for improved and targeted care. However, the impact of the nanoelectrodes on the body if they disconnected from their contact points has remained a mystery and point of concern. The researchers from Lund University (Lund, Sweden) joined forces to investigate this mystery by assessing the consequences of a potential worst-case scenario associated with the implantation of nanoscale electrodes.

To do so, the scientists injected rats’ brains with nanowires similar in size and shape to the registration nodes of proposed nanoelectrodes. The injected rats were then evaluated after 1, 6, and 12 weeks to study how their brains were reacting to the foreign nanowires.

“We studied two of the brain tissue’s support cells: On the one hand, microglia cells, whose job is to ‘tidy up’ junk and infectious compounds in the brain and, on the other hand, astrocytes, who contribute to the brain’s healing process,” notes Nils Danielsen, a researcher involved with the project. “The microglia ‘ate’ most of the nanowires. In weeks 6 and 12 we could see remains of them in the microglia cells.” Results indicated that permanent brain damage or injury was not sustained by injecting the nanowires. The researchers believe that this biocompatibility study could help to encourage progress in the development of nanoelectrodes.

When illuminated by laser light shining through a prism, a silicon chip coated with a gold film (center of apparatus) can pull particles out of a liquid solution flowing over the top. (Photo: Kenneth Crozier, Harvard University.)

Tiny chip-based optical devices that can attract particles out of a liquid using the force of photons could enable scientists to image and identify disease cells without the use of microscopes and lasers. Developed by a team of physicists at Harvard University (Cambridge, MA) led by Kenneth Crozier, associate professor of electrical engineering, these optical traps are designed to be integrated with microfluidic devices, some of which are currently in clinical trials for diagnosing cancer and monitoring patient response to therapies.

Usually costing tens of thousands of dollars, traditional optical traps require powerful lasers and microscopes to focus light onto particles as small as a single atom. In contrast, photons can transfer their momentum to atoms, molecules, or cells, enabling physicists to control the particle’s movement by holding it steady or by pulling on it to monitor its response. The Harvard group hopes to integrate these optical traps into microfluidic devices for sorting and imaging disease cells in the blood.

The optical traps developed by Crozier and Harvard researchers Ethan Schonbrun and Kai Wang can trap particles as strongly as more-complex systems. Microfluidic chips shuttle cells around in a fluid and typically control their movements using physical barriers and variations in pressure and voltage. The Harvard team’s optical traps can pull cells down to the surface of a chip for observation and then use them to sort the cells based on their identity.

Using manufacturing techniques common to the semiconducting industry, the Harvard researchers patterned chips with two different designs. One design is a silicon chip patterned with a ring with a radius of five µm. When illuminated by a laser, light resonates around the ring, generating an optical force that can pull particles from liquid flowing above the chip. The other design consists of a chip patterned with arrays of 64 bull’s-eye patterns. When illuminated, each of these can trap a flowing particle. Each pattern has the function of a confocal microscope and could be used to get a 3-D picture of a cell, Crozier explains.

Crozier’s team has developed a third design based on gold structures that can generate a form of light energy, or surface waves, called plasmons. When a smooth gold film is illuminated, the light couples to the surface in the form of plasmons, which generate forces that are very localized and strong. The Harvard researchers have shown that when long tapered gold films patterned on silicon chips are illuminated by light shining through a small prism, they can used to pull a particle down and then push it along the gold surface. By changing the angle of the light, the particle’s speed can be controlled. This type of structure will be particularly useful for cell sorting, Crozier remarks.

These types of systems might eventually replace clinical-laboratory devices called flow cytometers, says Holger Schmidt, professor of electrical engineering and director of the W. M. Keck Center for Nanoscale Optofluidics at the University of California, Santa Cruz. Today’s flow cytometers use bulky optical systems to separate cells in blood samples based on their size and shape. Chip-scale optics could do the same thing, but as portable devices, they could be brought to a patient’s bedside. These compact optical traps might be on the market in three to five years, notes Schmidt.