Particle Trap Paves Way for Personalized Medicine

But being able to isolate individual molecules like DNA base pairs, which are just two nanometers across -- or about 1/50,000th the diameter of a human hair -- is incredibly expensive and difficult to control. In addition, devising a way to trap DNA molecules in their natural aqueous environment further complicates things. Scientists have spent the past decade struggling to isolate and trap individual DNA molecules in an aqueous solution by trying to thread it through a tiny hole the size of DNA, called a"nanopore," which is exceedingly difficult to make and control.

Now a team led by Yale University researchers has proven that isolating individual charged particles, like DNA molecules, is indeed possible using a method called"Paul trapping," which uses oscillating electric fields to confine the particles to a space only nanometers in size. (The technique is named for Wolfgang Paul, who won the Nobel Prize for the discovery.) Until now, scientists have only been able to use Paul traps for particles in a vacuum, but the Yale team was able to confine a charged test particle -- in this case, a polystyrene bead -- to an accuracy of just 10 nanometers in aqueous solutions between quadruple microelectrodes that supplied the electric field.

Their device can be contained on a single chip and is simple and inexpensive to manufacture."The idea would be that doctors could take a tiny drop of blood from patients and be able to run diagnostic tests on it right there in their office, instead of sending it away to a lab where testing can take days and is expensive," said Weihua Guan, a Yale engineering graduate student who led the project.

In addition to diagnostics, this"lab-on-a-chip" would have a wide range of applications, Guan said, such as being able to analyze how individual cells respond to different stimulation. While there are several other techniques for cell-manipulation available now, such as optical tweezers, the Yale team's approach actually works better as the size of the targets gets smaller, contrary to other approaches.

The team, whose findings appear in the May 23 Early Edition of theProceedings of the National Academy of Sciences,used charged polystyrene beads rather than actual DNA molecules, along with a two-dimensional trap to prove that the technique worked. Next, they will work toward creating a 3-D trap using DNA molecules, which, at two nanometers, are even smaller than the test beads. They hope to have a working, 3-D trap using DNA molecules in the next year or two. The project is funded by a National Institutes of Health program that aims to sequence a patient's entire genome for less than$1,000.

"This is the future of personalized medicine," Guan said.

The project was directed by Mark Reed (Yale University) and Predrag Krstic (Oak Ridge National Laboratory). Other authors of the paper include Sony Joseph and Jae Hyun Park (Oak Ridge National Laboratory).

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Laser Modules in Matchbox Size

Compact laser modules from the Berlin-based Ferdinand-Braun-Institut (FBH) which are only the size of a matchbox open up various application areas. The flexible all-rounders can be optimized according to the specific demands made on lasers in material analytics, display technology as well as material processing.

The modules consist of several optoelectronic semiconductor chips (diode laser and amplifier) and adapted gallium nitride transistors. All chips have been developed at FBH and base on the institute's comprehensive know-how in semiconductor technology and chip development. Additionally, hybrid-integrated micro optics and non-linear crystals form the beam and transform the wavelength into the blue and green spectral region respectively. Within this spectral region, the modules now reach output powers exceeding 1.5 W with an excellent beam quality. Using a single-pass configuration enables simple frequency doubling and thus modules which can be realized specifically compact. They are particularly suitable for applications requiring low-noise performance, this means with as little undesired signals as possible, and fast modulation.

Efficient, pulsed laser beam sources offering high flexibility

The FBH additionally presents diode lasers which are, due to their flexibility, preferably used in laser systems for material processing. Mobile short-range LIDAR systems may also benefit from the efficient and compact diode lasers. One of such sources is a newly developed miniaturized pulsed laser module with 10 ps… 100 ns pulse width and a defined repetition rate in the kHz and MHz range. FBH also introduces these lasers at the accompanying symposium. With hybrid-integrated amplifiers they reach peak powers up to several 10 W.

With its gain-switching 1064 nm DFB laser diodes assembled with integrated electronics in a butterfly housing, which FBH showcases at the fair for the first time, the institute introduces further flexible light sources for the 1-100 ns time-domain. Without amplifier, their pulse powers are at 1.5 W in the time range 1-10 ns.

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Toward Faster Transistors: Physicists Discover Physical Phenomenon That Could Boost Computers' Clock Speed

In this week's issue of the journalScience,MIT researchers and their colleagues at the University of Augsburg in Germany report the discovery of a new physical phenomenon that could yield transistors with greatly enhanced capacitance -- a measure of the voltage required to move a charge. And that, in turn, could lead to the revival of clock speed as the measure of a computer's power.

In today's computer chips, transistors are made from semiconductors, such as silicon. Each transistor includes an electrode called the gate; applying a voltage to the gate causes electrons to accumulate underneath it. The electrons constitute a channel through which an electrical current can pass, turning the semiconductor into a conductor.

Capacitance measures how much charge accumulates below the gate for a given voltage. The power that a chip consumes, and the heat it gives off, are roughly proportional to the square of the gate's operating voltage. So lowering the voltage could drastically reduce the heat, creating new room to crank up the clock.

MIT Professor of Physics Raymond Ashoori and Lu Li, a postdoc and Pappalardo Fellow in his lab -- together with Christoph Richter, Stefan Paetel, Thilo Kopp and Jochen Mannhart of the University of Augsburg -- investigated the unusual physical system that results when lanthanum aluminate is grown on top of strontium titanate. Lanthanum aluminate consists of alternating layers of lanthanum oxide and aluminum oxide. The lanthanum-based layers have a slight positive charge; the aluminum-based layers, a slight negative charge. The result is a series of electric fields that all add up in the same direction, creating an electric potential between the top and bottom of the material.

Ordinarily, both lanthanum aluminate and strontium titanate are excellent insulators, meaning that they don't conduct electrical current. But physicists had speculated that if the lanthanum aluminate gets thick enough, its electrical potential would increase to the point that some electrons would have to move from the top of the material to the bottom, to prevent what's called a"polarization catastrophe." The result is a conductive channel at the juncture with the strontium titanate -- much like the one that forms when a transistor is switched on. So Ashoori and his collaborators decided to measure the capacitance between that channel and a gate electrode on top of the lanthanum aluminate.

They were amazed by what they found: Although their results were somewhat limited by their experimental apparatus, it may be that an infinitesimal change in voltage will cause a large amount of charge to enter the channel between the two materials."The channel may suck in charge -- shoomp! Like a vacuum," Ashoori says."And it operates at room temperature, which is the thing that really stunned us."

Indeed, the material's capacitance is so high that the researchers don't believe it can be explained by existing physics."We've seen the same kind of thing in semiconductors," Ashoori says,"but that was a very pure sample, and the effect was very small. This is a super-dirty sample and a super-big effect." It's still not clear, Ashoori says, just why the effect is so big:"It could be a new quantum-mechanical effect or some unknown physics of the material."

There is one drawback to the system that the researchers investigated: While a lot of charge will move into the channel between materials with a slight change in voltage, it moves slowly -- much too slowly for the type of high-frequency switching that takes place in computer chips. That could be because the samples of the material are, as Ashoori says,"super dirty"; purer samples might exhibit less electrical resistance. But it's also possible that, if researchers can understand the physical phenomena underlying the material's remarkable capacitance, they may be able to reproduce them in more practical materials.

Triscone cautions that wholesale changes to the way computer chips are manufactured will inevitably face resistance."So much money has been injected into the semiconductor industry for decades that to do something new, you need a really disruptive technology," he says.

"It's not going to revolutionize electronics tomorrow," Ashoori agrees."But this mechanism exists, and once we know it exists, if we can understand what it is, we can try to engineer it."

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Forecast Calls for Nanoflowers to Help Return Eyesight: Physicist Leads Effort to Design Fractal Devices to Put in Eyes

These flowers are not roses, tulips or columbines. They will be nanoflowers seeded from nano-sized particles of metals that grow, or self assemble, in a natural process -- diffusion limited aggregation. They will be fractals that mimic and communicate efficiently with neurons.

Fractals are"a trademark building block of nature," Taylor says. Fractals are objects with irregular curves or shapes, of which any one component seen under magnification is also the same shape. In math, that property is self-similarity. Trees, clouds, rivers, galaxies, lungs and neurons are fractals, Taylor says. Today's commercial electronic chips are not fractals, he adds.

Eye surgeons would implant these fractal devices within the eyes of blind patients, providing interface circuitry that would collect light captured by the retina and guide it with almost 100 percent efficiency to neurons for relay to the optic nerve to process vision.

In an article titled"Vision of beauty" forPhysics World, Taylor, a physicist and director of the UO Materials Science Institute, describes his envisioned approach and how it might overcome the problems occurring with current efforts to insert photodiodes behind the eyes. Current chip technology is limited, because it doesn't allow sufficient connections with neurons.

"The wiring -- the neurons -- in the retina is fractal, but the chips are not fractal," Taylor says."They are just little squares of electrodes that provide too little overlap with the neurons."

Beginning this summer, Taylor's doctoral student Rick Montgomery will begin a yearlong collaboration with Simon Brown at the University of Canterbury in New Zealand to experiment with various metals to grow the fractal flowers on implantable chips.

The idea for the project emerged as Taylor was working under a Cottrell Scholar Award he received in 2003 from the Research Corporation for Science Advancement. His vision is now beginning to blossom under grants from the Office of Naval Research (ONR), the U.S. Air Force and the National Science Foundation.

Taylor's theoretical concept for fractal-based photodiodes also is the focus of a U.S. patent application filed by the UO's Office of Technology Transfer under Taylor's and Brown's names, the UO and University of Canterbury.

The project, he writes in thePhysics Worldarticle, is based on"the striking similarities between the eye and the digital camera." (Physics Worldarticle is available at:http://physicsworld.com/cws/article/indepth/45840)

"The front end of both systems," he writes,"consists of an adjustable aperture within a compound lens, and advances bring these similarities closer each year." Digital cameras, he adds, are approaching the capacity to capture the 127 megapixels of the human eye, but current chip-based implants, because of their interface, are only providing about 50 pixels of resolution.

Among the challenges, Taylor says, is determining which metals can best go into body without toxicity problems."We're right at the start of this amazing voyage," Taylor says."The ultimate thrill for me will be to go to a blind person and say, we're developing a chip that one day will help you see again. For me, that is very different from my previous research, where I've been looking at electronics to go into computers, to actually help somebody… if I can pull that off that will be a tremendous thrill for me."

Taylor also is working under a Research Corp. grant to pursue fractal-based solar cells.

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Optical Microscope Without Lenses Produces High-Resolution 3-D Images on a Chip

The advance, featured in the early online edition of the journalProceedings of the National Academy of Sciences, represents the first demonstration of lens-free optical tomographic imaging on a chip, a technique capable of producing high-resolution 3-D images of large volumes of microscopic objects.

"This research clearly shows the potential of lens-free computational microscopy," said Aydogan Ozcan, senior author of the research and an associate professor of electrical engineering at UCLA's Henry Samueli School of Engineering and Applied Science."Wonderful progress has been made in recent years to miniaturize life-sciences tools with microfluidic and lab-on-a-chip technologies, but until now optical microscopy has not kept pace with the miniaturization trend."

An optical imaging system small enough to fit onto an opto-electronic chip provides a variety of benefits. Because of the automation involved in on-chip systems, scientific work could be sped up significantly, which might have a great impact in the fields of cell and developmental biology. In addition, the small size not only has great potential for miniaturizing systems but also leads to cost savings on equipment.

The optical microscope, invented more than 400 years ago, has tended to grow larger and more complex as it has been modified to image ever-smaller objects with better resolution. To address this lack of progress in miniaturization, Ozcan's research group -- with graduate student Serhan Isikman and postdoctoral scholar Waheb Bishara as lead researchers -- developed the new tomographic microscopy platform through the next evolution of a lens-free imaging technology the group created and has been improving for years.

Ozcan, a researcher at the California NanoSystems Institute at UCLA, makes the analogy that a traditional optical microscope is like a huge set of pipes delivering content, in the form of images, to the user. Over years of development, bottlenecks occur that impede further improvement. Even if one part of the system -- that is, one bottleneck -- is improved, other bottlenecks keep that improvement from being fully realized. Not so with the lens-free system, according to Ozcan.

"Lens-free imaging removes the pipes altogether by utilizing an entirely new design," he said.

The system takes advantage of the fact that organic structures, such as cells, are partially transparent. So by shining a light on a sample of cells, the shadows created reveal not only the cells' outlines but details about their sub-cellular structures as well.

"These details can be captured and analyzed if the shadow is directed onto a digital sensor array," Isikman said."The end result of this process is an image taken without using a lens."

Ozcan envisions this lens-free imaging system as one component in a lab-on-a-chip platform. It could potentially fit beneath a microfluidic chip, a tool for the precise control and manipulation of sub-millimeter biological samples and fluids, and the two tools would operate in tandem, with the microfluidic chip depositing and subsequently removing a sample from the lens-free imager in an automated, or high-throughput, process.

The platform's 3-D images are created by rotating the light source to illuminate the samples from multiple angles. These multiple angles also allow the system to utilize tomography, a powerful imaging technique. Through the use of tomography, the system is able to produce 3-D images without sacrificing resolution.

"The field of view of lens-based microscopes is limited because the lens focuses on a narrow area of a sample," Bishara said."A lens-free microscope has both a much larger field of view and depth of field because the imaging is done by the digital sensor array and is not constrained by a lens."

The research was funded by grants from the National Science Foundation, the U.S. Office of Naval Research and the National Institutes of Health and was also supported by the Gates Foundation and the Vodafone Americas Foundation.

For more information on the Ozcan research group, visithttp://innovate.ee.ucla.edu/.

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Controlled Production of Nanometric Drops

The study details the different physical conditions needed to destabilize a fluid and create droplets according to the wetting properties of the surface it is in contact with. Ignasi Pagonabarraga, a lecturer with the Department of Fundamental Physics and one of the authors of the study, explains that"the interaction of the fluid with the surface can be used to control the size of the drops and the time they take to form. Although there are other methods for creating micrometric droplets, the affinity of liquids to solid surfaces creates a more versatile environment for the production and control of drops down to the nanoscale."

According to Aurora Hernández-Machado, a lecturer with the UB's Department of Structure and Constituents of Matter and co-author of the study,"miniaturization in liquids is important in increasing efficiency and optimizing the rate of consumption of substances such as pharmaceutical products, cosmetics and ink, which would enable us to lower the cost of processes associated with the production and control of these products. In addition, the physical model, which we could define as a microfluidic dispenser for various substances, allows us to overcome the limitations traditionally associated with drop formation processes and to create submicrometre-scale droplets."

One of the fields to which this type of process is most readily applicable is the development of lab-on-a-chip (LOC) devices, which integrate a range of laboratory analysis functions into a miniaturized chip format and need only very small volumes of liquid to perform the analyses. The dynamics involved in the formation of submicrometre-scale drops have various technological applications in other fields, for example in controlled drug administration or in the creation of emulsions such as those used in certain types of cosmetic products formed by micro-droplets of substances with specific properties within another fluid. Other applications include ink distribution in printers.

In physical terms, the drops are formed due to instability in the fluid. The study describes a wetting-based destabilization mechanism of forced microfilaments that affects adherence to difference surfaces. The researchers have been able to establish the balance of forces that determines the drop emission mechanism, which involves the capillarity of the fluid, the viscous friction of the solid surface and gravity. This balance and the size of the liquid filaments determine the size of the drops emitted, which in some cases are nanometric. It has also been observed that the emission of drops depends to a great extent on the static wetting angle, that is, the angle that the drop makes with the contact surface. The greater this angle the higher the degree of hydrophobia of the surface in question.

In the experiments carried out for the study, focusing on water in air, the team of researchers has demonstrated the operation of the microfluidic model and created drops at the micrometre scale, but the model is also capable of producing nanometric droplets. Tests have been carried out using a range of supports from hydrophilic surfaces to superhydrophobic substrates, and the authors show how wetting can be used to pinpoint the wetting-controlled emission point. By varying the chemical and nanostructural properties of the surface in question, it is possible to alter the wetting angle and control the drop formation dynamics.

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First Macro-Scale Thin-Film Solid-Oxide Fuel Cell: Strong, Nanostructured Membrane Enables Scaling for Clean-Energy Applications

While SOFCs have previously worked at the micro-scale, this is the first time any research group has overcome the structural challenges of scaling the technology up to a practical size with a proportionally higher power output.

Reported online April 3 inNature Nanotechnology, the demonstration of this fully functional SOFC indicates the potential of electrochemical fuel cells to be a viable source of clean energy.

"The breakthrough in this work is that we have demonstrated power density comparable to what you can get with tiny membranes, but with membranes that are a factor of a hundred or so larger, demonstrating that the technology is scalable," says principal investigator Shriram Ramanathan, Associate Professor of Materials Science at SEAS.

SOFCs create electrical energy via an electrochemical reaction that takes place across an ultra-thin membrane. This 100-nanometer membrane, comprising the electrolyte and electrodes, has to be thin enough to allow ions to pass through it at a relatively low temperature (which, for ceramic fuel cells, lies in the range of 300 to 500 degrees Celsius). These low temperatures allow for a quick start-up, a more compact design, and less use of rare-earth materials.

So far, however, thin films have been successfully implemented only in micro-SOFCs, where each chip in the fuel cell wafer is about 100 microns wide. For practical applications, such as use in compact power sources, SOFCs need to be about 50 times wider.

The electrochemical membranes are so thin that creating one on that scale is roughly equivalent to making a 16-foot-wide sheet of paper. Naturally, the structural issues are significant.

"If you make a conventional thin membrane on that scale without a support structure, you can't do anything -- it will just break," says co-author Bo-Kuai Lai, a postdoctoral fellow at SEAS."You make the membrane in the lab, but you can't even take it out. It will just shatter."

With lead author Masaru Tsuchiya (Ph.D. '09), a former member of Ramanathan's lab who is now at SiEnergy, Ramanathan and Lai fortified the thin film membrane using a metallic grid that looks like nanoscale chicken wire.

The tiny metal honeycomb provides the critical structural element for the large membrane while also serving as a current collector. Ramanathan's team was able to manufacture membrane chips that were 5 mm wide, combining hundreds of these chips into palm-sized SOFC wafers.

While other researchers' earlier attempts at implementing the metallic grid showed structural success, Ramanathan's team is the first to demonstrate a fully functional SOFC on this scale. Their fuel cell's power density of 155 milliwatts per square centimeter (at 510 degrees Celsius) is comparable to the power density of micro-SOFCs.

When multiplied by the much larger active area of this new fuel cell, that power density translates into an output high enough for relevance to portable power.

Previous work in Ramanathan's lab has developed micro-SOFCs that are all-ceramic or that use methane as the fuel source instead of hydrogen. The researchers hope that future work on SOFCs will incorporate these technologies into the large-scale fuel cells, improving their affordability.

In the coming months, they will explore the design of novel nanostructured anodes for hydrogen-alternative fuels that are operable at these low temperatures and work to enhance the microstructural stability of the electrodes.

The research was supported in part by the National Science Foundation (NSF) and performed in part at the Harvard University Center for Nanoscale Systems, a member of the NSF-funded National Nanotechnology Infrastructure Network.

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