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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