Throw away the detergent and forgo the elbow grease: pesky proteins can now be removed from surfaces by simply exposing them to light, thanks to a reusable titania template developed by A*STAR researchers ("Fabrication of Self-Cleaning, Reusable Titania Templates for Nanometer and Micrometer Scale Protein Patterning"). Biologists have many reasons to pattern surfaces with proteins, from creating highly selective biosensors to studying fundamental processes such as tissue formation. What they don’t want, however, is for the proteins to stay on the surface indefinitely. Unfortunately, ridding a surface of proteins is a complicated and time-consuming task, which means that the majority of biologists typically throw away their substrates after a single use — leading to a high cost for consumables. Moreover, due to the complexity of fabrication systems, biologists usually outsource their chip manufacturing to engineers, which introduces delays and further exacerbates cost. Karen Chong and her team at the A*STAR Institute of Materials Research and Engineering in Singapore recognized that these delays and costs could be avoided by designing a fabrication technique that non-engineers could use. “We wanted to demonstrate that fabrication and patterning techniques could move away from the traditional domains of microelectronics,” she recalls. “Specifically, we wanted to create fabrication techniques that could easily be adopted and replicated by biologists.” Chong notes that to be practical, fabrication techniques must be either easy to use or have the potential to be scaled up to produce commercial quantities. Consequently, she and the team focused on two techniques: interferometric lithography for the former and nanoimprint lithography for the latter. “Interferometric lithography techniques can be easily replicated by biologists without the need for a very complex or costly set-up in their laboratories,” she explains. “While nanoimprinting is not practical for smaller labs, it does allow us to scale up these samples into larger-area substrates.” Both approaches yielded surfaces with titania nanostructures (see image) that were then covered with protein-resistant silanes. Exposure to ultraviolet light degrades the silanes, which allows proteins to adhere to the selected regions. After the protein-patterned substrates have served their purpose, Chong describes how “the proteins on the chips can be quickly removed, by just exposing the used substrates to ultraviolet light, without the need for elaborate cleaning methods.” The substrates can then be immediately reused without the need for further preparation. “With the recyclable chip and the technique that we have demonstrated, fabrication techniques are no longer the exclusive domain of engineers,” remarks Chong.
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Quantum dots light the way
Polymer nanoparticles that release medicine at controlled rates inside cells have the potential to enhance the efficacy of many clinical drugs. A*STAR researchers have now developed an eye-catching way to evaluate the performance of different polymer drug-delivery formulations using luminescent quantum dots as imaging labels ("Evaluation of Polymeric Nanoparticle Formulations by Effective Imaging and Quantitation of Cellular Uptake for Controlled Delivery of Doxorubicin"). 
Confocal images of quantum dots localized within colon cells can guide the development of innovative drug delivery formulations. (© Wiley-VCH Verlag) Tiny, inorganic quantum-dot crystals are finding increasing use as biological probes due to their powerful optical characteristics. By stimulating the dots with laser light, researchers can obtain sharp images to monitor processes such as drug delivery for much longer time frames than nearly any other technique. However, a key challenge lies in incorporating hydrophobic quantum dots into biocompatible, water-soluble polymers. Ming-Yong Han and co-workers from the A*STAR Institute of Materials Research and Engineering in Singapore turned to a copolymer known as poly(D,L-lactide-co-glycolide), or PLGA, for their quantum-dot imaging strategy. This non-toxic material has tunable water-repelling or water-attracting ability, depending on the proportion of lactic and glycolic acid components. It is also an ideal drug delivery platform for the popular anticancer drug doxorubicin — a fluorescent molecule used to treat diseases including leukemia and Hodgkin’s lymphoma. “The choice of polymer and nanoparticle preparations plays an important role in making uniformly fluorescent particles,” says co-author Choon Peng Teng. “Different hydrophobic or hydrophilic interactions affect how quantum dots are incorporated.” The team synthesized two kinds of PLGA nanoparticles — one loaded with doxorubicin, and the other containing quantum-dot bio-labels — and incubated them in a culture of human colon cells. After two hours, confocal imaging revealed that both kinds of polymer nanoparticles were engulfed by the cells through an endocytosis mechanism and internalized into the cytoplasm (see image). The bright emissions from the dots enabled the researchers to quantify the uptake as 25 per cent of the cell volume. Since the behavior of the quantum dot-labeled nanoparticles paralleled the doxorubicin-impregnated materials, Han and colleagues realized this imaging system could model the effectiveness of other important drug-delivery schemes. Initial investigations appear promising — the quantum-dot-loaded PLGA nanoparticles mimicked different drug-delivery systems for targeting brain, lung and breast cancer cell lines, and were compatible with both water-soluble and water-insoluble drugs. One further advantage of this approach, notes co-author Khin Yin Win, is that it can simulate the action of non-fluorescent anticancer drugs previously untraceable with confocal imaging. “This model can facilitate monitoring biocompatibility and cellular uptake, but it can also evaluate how feasible certain materials are as drug carriers,” she says. “This could lead to more innovative drug-delivery systems.”
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Confocal images of quantum dots localized within colon cells can guide the development of innovative drug delivery formulations. (© Wiley-VCH Verlag) Tiny, inorganic quantum-dot crystals are finding increasing use as biological probes due to their powerful optical characteristics. By stimulating the dots with laser light, researchers can obtain sharp images to monitor processes such as drug delivery for much longer time frames than nearly any other technique. However, a key challenge lies in incorporating hydrophobic quantum dots into biocompatible, water-soluble polymers. Ming-Yong Han and co-workers from the A*STAR Institute of Materials Research and Engineering in Singapore turned to a copolymer known as poly(D,L-lactide-co-glycolide), or PLGA, for their quantum-dot imaging strategy. This non-toxic material has tunable water-repelling or water-attracting ability, depending on the proportion of lactic and glycolic acid components. It is also an ideal drug delivery platform for the popular anticancer drug doxorubicin — a fluorescent molecule used to treat diseases including leukemia and Hodgkin’s lymphoma. “The choice of polymer and nanoparticle preparations plays an important role in making uniformly fluorescent particles,” says co-author Choon Peng Teng. “Different hydrophobic or hydrophilic interactions affect how quantum dots are incorporated.” The team synthesized two kinds of PLGA nanoparticles — one loaded with doxorubicin, and the other containing quantum-dot bio-labels — and incubated them in a culture of human colon cells. After two hours, confocal imaging revealed that both kinds of polymer nanoparticles were engulfed by the cells through an endocytosis mechanism and internalized into the cytoplasm (see image). The bright emissions from the dots enabled the researchers to quantify the uptake as 25 per cent of the cell volume. Since the behavior of the quantum dot-labeled nanoparticles paralleled the doxorubicin-impregnated materials, Han and colleagues realized this imaging system could model the effectiveness of other important drug-delivery schemes. Initial investigations appear promising — the quantum-dot-loaded PLGA nanoparticles mimicked different drug-delivery systems for targeting brain, lung and breast cancer cell lines, and were compatible with both water-soluble and water-insoluble drugs. One further advantage of this approach, notes co-author Khin Yin Win, is that it can simulate the action of non-fluorescent anticancer drugs previously untraceable with confocal imaging. “This model can facilitate monitoring biocompatibility and cellular uptake, but it can also evaluate how feasible certain materials are as drug carriers,” she says. “This could lead to more innovative drug-delivery systems.”
Optical materials - Two crystals are better than one
A method for designing materials capable of slowing the propagation of light over a broad range of wavelengths has been developed by researchers at the A*STAR Institute of High Performance Computing ("Broadband slow light in one-dimensional logically combined photonic crystals"). 
Combining photonic crystals can slow the propagation of light for applications in optical communications. (Image: A*STAR Institute of High Performance Computing) The speed of light in a vacuum is always constant — a fundamental concept made famous by Albert Einstein. But light propagates more slowly when it enters a different medium, such as glass. The degree to which the speed is reduced is given by a material’s dielectric constant — a higher dielectric constant indicates slower propagation. Rather than rely on a limited source of natural substances, scientists have started to design optical materials with a broader range of beneficial properties including ‘slow’ light. One approach is to combine two materials with different dielectric constants into a periodic structure. This can result in properties that dramatically differ from those of the constituent materials, particular when the length scale of the periodicity is similar to the wavelength of light. “These so-called photonic crystals, when appropriately designed and in ideal conditions, can almost stop the propagation of light altogether,” says A*STAR scientist Gandhi Alagappan. The requirement that the periodicity of the structure be similar to the wavelength of interest, however, is a limitation for practical applications. It means that most of these materials only work with light of a single color. Alagappan and his co-worker Jason Ching Png have now developed a scheme for designing photonic crystals that operate over a broader range of wavelengths. Alagappan and Png considered a structure in which two different materials are layered on top of each other. To obtain two different periodicities, however, a third material with a dielectric constant midway between the two other materials would typically be needed. This makes physically creating the structure difficult. The researchers instead focused on developing a mathematical technique to combine two materials in such a way that the dielectric profile in the stacking direction is almost the same as in the more complicated three-material structure (see image). Alagappan and Png simulated the optical properties of their combined photonic crystal. They identified a broad range of wavelengths known as the strong coupling region that has a high density of slow modes. “We have invented a linear optical multi-scale architecture that facilitates the creation of broadband slow light,” says Alagappan. “The proposed structure could potentially revolutionize current optical buffering technologies.”
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Combining photonic crystals can slow the propagation of light for applications in optical communications. (Image: A*STAR Institute of High Performance Computing) The speed of light in a vacuum is always constant — a fundamental concept made famous by Albert Einstein. But light propagates more slowly when it enters a different medium, such as glass. The degree to which the speed is reduced is given by a material’s dielectric constant — a higher dielectric constant indicates slower propagation. Rather than rely on a limited source of natural substances, scientists have started to design optical materials with a broader range of beneficial properties including ‘slow’ light. One approach is to combine two materials with different dielectric constants into a periodic structure. This can result in properties that dramatically differ from those of the constituent materials, particular when the length scale of the periodicity is similar to the wavelength of light. “These so-called photonic crystals, when appropriately designed and in ideal conditions, can almost stop the propagation of light altogether,” says A*STAR scientist Gandhi Alagappan. The requirement that the periodicity of the structure be similar to the wavelength of interest, however, is a limitation for practical applications. It means that most of these materials only work with light of a single color. Alagappan and his co-worker Jason Ching Png have now developed a scheme for designing photonic crystals that operate over a broader range of wavelengths. Alagappan and Png considered a structure in which two different materials are layered on top of each other. To obtain two different periodicities, however, a third material with a dielectric constant midway between the two other materials would typically be needed. This makes physically creating the structure difficult. The researchers instead focused on developing a mathematical technique to combine two materials in such a way that the dielectric profile in the stacking direction is almost the same as in the more complicated three-material structure (see image). Alagappan and Png simulated the optical properties of their combined photonic crystal. They identified a broad range of wavelengths known as the strong coupling region that has a high density of slow modes. “We have invented a linear optical multi-scale architecture that facilitates the creation of broadband slow light,” says Alagappan. “The proposed structure could potentially revolutionize current optical buffering technologies.”
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