Microelectromechanical based systems

UC San Diego researchers developing better tissue scaffolds.

University of California, San Diego NanoEngineers won a grant from the National Institutes of Health (NIH) to develop the tools to manufacture biodegradable frames around which heart tissues – functional blood vessels included – will grow. Developing methods for growing tissues that mimic nature’s fine-grained details, including vasculature, could lead to breakthroughs in efforts to grow replacement cardiac tissues for people who have suffered a heart attack. The work could also lead to better systems for growing and studying cells, including stem cells, in the laboratory.

Professor Shaochen Chen from the UC San Diego Department of NanoEngineering is the Principal Investigator on the four-year $1.5 million grant from the National Institutes of Health. The grant is funding development of the manufacturing platform necessary to produce these biodegradable frames or “scaffolds.”

“We are creating biomaterials with nanostructures on the inside,” said Chen. “Scientifically there are so many opportunities at the molecular level, and nanoengineering is a perfect fit for that. We expect our new biofabrication platform will yield tissues that mimic natural tissues much more closely.”

Caption: University of California, San Diego, nanoengineers won a grant from the National Institutes of Health to develop the tools to manufacture biodegradable frames around which heart tissues — functional blood vessels included — will grow. Developing methods for growing tissues that mimic nature’s fine-grained details, including vasculature, could lead to breakthroughs in efforts to grow replacement cardiac tissues for people who have suffered a heart attack. The work could also lead to better systems for growing and studying cells, including stem cells, in the laboratory. Credit: Shaochen Chen. Usage Restrictions: Shaochen Chen.

One such opportunity is to add new levels of precision and functionality to the scaffolds produced by the “biofabrication platform” that Chen and his collaborators invented and have been improving over the last five years. With the improved biofabrication platform, engineers in the Department of NanoEngineering within the UC San Diego Jacobs School of Engineering will be able to produce scaffolds with precisely designed systems of nanoscale pores and other microarchitectural details that control how cells interact with each other and with the environment. “You need to design the pores so the cell can get nutrition and dump waste…pathways for the cell to survive in the system,” explained Chen. The researchers also plan to create scaffolds with tubes, and then seed those tubes with the cells that line blood vessels – endothelial cells – in order to try to generate functioning vascular systems. The lack of blood vessels in most tissue regeneration systems results in cell death, loss of function, and limits the maximum size of regenerated tissues.

In addition, the chemical properties of the new scaffolds will change from top to bottom, which will create chemical gradients that drive cell growth.

As in previous versions of Chen’s scaffold-building system, cells will be encapsulated within scaffold walls.

“Usually, when researchers grow tissue, they make a scaffold, put the cells in the scaffold and let the cells grow,” explained Chen. “When we fabricate our scaffolds, the cells are already inside the scaffold walls.” Encapsulating cells within the walls encourages uniform seeding of cells.

The scaffolds will be based on natural materials such as hyaluronic acid, a key component of the “extracellular matrix” that provides structural support, wound healing, and a range of other functions to human and other animal tissues.

“The hydrogels for our scaffolds can’t be too soft, too sticky or too rigid. They need to fit the needs of the biological tissue,” said Chen.

Collaborators at Harvard Medical School will grow and characterize the tissues started on the scaffolds.

Projection Bioprinting

To manufacture tissue scaffolds, Chen and colleagues have developed and continue to refine a manufacturing process that uses light, precisely controlled mirrors, and a computer projection system. First, the engineers design a three dimensional model of the structure to be printed. Next, the engineers prepare a solution containing both the cells that will eventually grow into the tissue and the polymers that will solidify into the scaffold. When light shines into the solution using the series of mirrors, the scaffold solidifies according to the exact specifications of the projected image.

Following these steps, scaffolds are manufactured and cells are encapsulated in scaffold walls as light solidifies the polymers one layer at a time.

“With our biofabrication platform, we can build arbitrary, three-dimensional shapes, like branches of blood vessels, and tubes – large and small,” said Chen. My focus is on the materials fabrication and devices level. This work is applicable to many different types of cells and tissues.” ###

Shaochen Chen joined the faculty of the Department of NanoEngineering at UC San Diego in July, 2010. Chen is also a faculty member of the UC San Diego Institute of Engineering in Medicine.

Contact: Daniel Kane dbkane@ucsd.edu 858-534-3262 University of California – San Diego

Smoothing the edges

Researchers at the Georgia Institute of Technology have developed a new “templated growth” technique for fabricating nanometer-scale graphene devices. The method addresses what had been a significant obstacle to the use of this promising material in future generations of high-performance electronic devices.

The technique involves etching patterns into the silicon carbide surfaces on which epitaxial graphene is grown. The patterns serve as templates directing the growth of graphene structures, allowing the formation of nanoribbons of specific widths without the use of e-beams or other destructive cutting techniques. Graphene nanoribbons produced with these templates have smooth edges that avoid electron-scattering problems.

“Using this approach, we can make very narrow ribbons of interconnected graphene without the rough edges,” said Walt de Heer, a professor in the Georgia Tech School of Physics.

Using a new “templated growth” technique, researchers have fabricated an array of 10,000 graphene transistors.

“Anything that can be done to make small structures without having to cut them is going to be useful to the development of graphene electronics because if the edges are too rough, electrons passing through the ribbons scatter against the edges and reduce the desirable properties of graphene.”

The new technique has been used to fabricate an array of 10,000 top-gated graphene transistors on a 0.24 square centimeter chip – believed to be the largest density of graphene devices reported so far.

The research was reported Oct. 3 in the advance online edition of the journal Nature Nanotechnology. The work was supported by the National Science Foundation, the W.M. Keck Foundation and the Nanoelectronics Research Initiative Institute for Nanoelectronics Discovery and Exploration (INDEX).

In creating their graphene nanostructures, De Heer and his research team first use conventional microelectronics techniques to etch tiny “steps” – or contours – into a silicon carbide wafer. They then heat the contoured wafer to approximately 1,500 degrees Celsius, which initiates melting that polishes any rough edges left by the etching process.

They then use established techniques for growing graphene from silicon carbide by driving off the silicon atoms from the surface. Instead of producing a consistent layer of graphene one atom thick across the surface of the wafer, however, the researchers limit the heating time so that graphene grows only on the edges of the contours.

To do this, they take advantage of the fact that graphene grows more rapidly on certain facets of the silicon carbide crystal than on others. The width of the resulting nanoribbons is proportional to the depth of the contour, providing a mechanism for precisely controlling the nanoribbons. To form complex graphene structures, multiple etching steps can be carried out to create a complex template, de Heer explained.

“By using the silicon carbide to provide the template, we can grow graphene in exactly the sizes and shapes that we want,” he said. “Cutting steps of various depths allows us to create graphene structures that are interconnected in the way we want them to be.

In nanometer-scale graphene ribbons, quantum confinement makes the material behave as a semiconductor suitable for creation of electronic devices. But in ribbons a micron or more wide, the material acts as a conductor. Controlling the depth of the silicon carbide template allows the researchers to create these different structures simultaneously, using the same growth process.

“The same material can be either a conductor or a semiconductor depending on its shape,” noted de Heer, who is also a faculty member in Georgia Tech’s National Science Foundation-supported Materials Research Science and Engineering Center (MRSEC). “One of the major advantages of graphene electronics is to make the device leads and the semiconducting ribbons from the same material. That’s important to avoid electrical resistance that builds up at junctions between different materials.”

After formation of the nanoribbons – which can be as narrow as 40 nanometers – the researchers apply a dielectric material and metal gate to construct field-effect transistors. While successful fabrication of high-quality transistors demonstrates graphene’s viability as an electronic material, de Heer sees them as only the first step in what could be done with the material.

“When we manage to make devices well on the nanoscale, we can then move on to make much smaller and finer structures that will go beyond conventional transistors to open up the possibility for more sophisticated devices that use electrons more like light than particles,” he said. “If we can factor quantum mechanical features into electronics, that is going to open up a lot of new possibilities.”

De Heer and his research team are now working to create smaller structures, and to integrate the graphene devices with silicon. The researchers are also working to improve the field-effect transistors with thinner dielectric materials.

Ultimately, graphene may be the basis for a generation of high-performance devices that will take advantage of the material’s unique properties in applications where the higher cost can be justified. Silicon will continue to be used in applications that don’t require such high performance, de Heer said.

“This is another step showing that our method of working with epitaxial graphene on silicon carbide is the right approach and the one that will probably be used for making graphene electronics,” he added. “This is a significant new step toward electronics manufacturing with graphene.” ###

In addition to those already mentioned, the research has involved M. Sprinkle, M. Ruan, Y Hu, J. Hankinson, M. Rubio-Roy, B. Zhang, X. Wu and C. Berger.

Research News & Publications Office Georgia Institute of Technology 75 Fifth Street, N.W., Suite 314 Atlanta, Georgia 30308 USA

Contact: John Toon jtoon@gatech.edu 404-894-6986 Georgia Institute of Technology Research News

Oxford, UK. Oxford Nanopore Technologies Ltd (“Oxford Nanopore”) today announced an exclusive agreement with Harvard University’s Office of Technology Development (“Harvard”) for the development of graphene for DNA sequencing. Graphene is a robust, single atom thick ‘honeycomb’ lattice of carbon with high electrical conductivity. These properties make it an ideal material for high resolution, nanopore-based sequencing of single DNA molecules.

Under the terms of the agreement, Oxford Nanopore has exclusive rights to develop and commercialize methods for the use of graphene for the analysis of DNA and RNA, developed in the Harvard laboratories of Professors Jene Golovchenko, Daniel Branton, and Charles Lieber. The agreement adds to an existing collaboration between Oxford Nanopore and Harvard that spans basic methods of nanopore sensing through to the use of solid-state nanopores. Oxford Nanopore will also continue to support fundamental nanopore research at Harvard.

“Graphene is emerging as a wonder material for the 21st century and recent research has shown that it has transformative potential in DNA sequencing.” said Dr Gordon Sanghera, CEO of Oxford Nanopore Technologies. “The groundbreaking research at Harvard lays the foundation for the development of a novel solid-state DNA sequencing device. We are proud to partner with the research team that pioneered early nanopore discoveries and continues to break boundaries with new materials and techniques.

Caption: A nanopore is created in graphene to form a trans-electrode, measuring variations in current as a single DNA molecule passes through the pore. Credit: iemedia solutions/ONT. Usage Restrictions: None.

“Oxford Nanopore is probably best known for protein nanopores,” continued Dr Sanghera. “However, today’s agreement highlights that we are increasing our investment in solid-state nanopores by adding graphene to our existing portfolio of solid-state nanopore projects and collaborations.” In a landmark 2010 Nature publication (S. Garaj et al, Nature Vol 467,doi:10.1038/nature09379) the Harvard team and collaborators used graphene to separate two chambers containing ionic solutions, and created a hole – a nanopore – in the graphene. The group demonstrated that the graphene nanopore could be used as a trans-electrode, measuring a current flowing through the nanopore between two chambers. The trans-electrode was used to measure variations in the current as a single molecule of DNA was passed through the nanopore. This resulted in a characteristic electrical signal that reflected the size and conformation of the DNA molecule.

At one atom thick, graphene is believed to be the thinnest membrane able to separate two liquid compartments from each other. This is an important characteristic for DNA sequencing; a trans-electrode of this thickness would be suitable for the accurate analysis of individual bases on a DNA polymer as it passes through the graphene.

Nanopore techniques aim to improve substantially the cost, power and complexity of DNA sequencing. While first generation technologies in development at Oxford Nanopore use nanopores made by porous proteins, subsequent generations will use synthetic ‘solid-state’ materials such as silicon nitride. However, at this time challenges remain in industrial fabrication of synthetic nanopores with the required dimensions and electronic properties. Graphene offers a potential solution due to its strength, dimensions, electrical properties and future potential for low-cost manufacturing.

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Oxford Nanopore Technologies

Oxford Nanopore Technologies Ltd is developing a novel technology for direct, electronic detection and analysis of single molecules using nanopores. The GridION technology platform (x.co/Trk2) is designed to offer substantial benefits in a variety of applications; the Company’s lead application is DNA sequencing but the platform is adaptable for the analysis of proteins and other single molecules.

DNA sequencing techniques in development include exonuclease sequencing and strand sequencing, both of which combine a protein nanopore with a processive enzyme, multiplexed on a silicon chip. The Company also has collaborations for the development of solid-state nanopores.

Oxford Nanopore has collaborations and exclusive licensing deals with leading institutions including the University of Oxford, Harvard and UCSC. The Company has funding programmes in these laboratories to support the science of nanopore sensing. Oxford Nanopore has licensed or owns more than 250 patents and patent applications that relate to all aspects of nanopore sensing from protein nanopores to solid state nanopores and for the analysis of DNA, proteins and other molecules. This includes the use of functionalised solid-state nanopores for molecular characterisation, methods of fabricating solid-state nanopores and modifications of solid-state nanopores to adjust sensitivity or other parameters. For more information about the Company’s patent x.co/Trk1

For further information about the company please visit www.nanoporetech.com.

Notes to Editors Nature publication 1Graphene as a subnanometre trans-electrode membrane, S. Garaj, W. Hubbard, A. Reina, J. Kong, D. Branton & J. A. Golovchenko. Nature Vol 467,doi:10.1038/nature09379 (Sept 2010) www.nature.com/nature/journal/v467/n7312/abs/nature09

This publication describes the use of graphene as a trans-electrode, detecting a DNA strand as it passes through a hole in the graphene sheet.

A sheet of graphene was stretched over a silicon-based frame, and inserted between two separate liquid reservoirs. An electrical voltage was applied between the reservoirs and when a nanopore was formed in the graphene this allowed the flow of an ionic current through the nanopore. This current could be measured as an electrical current signal using the trans-electrode properties of graphene.

Double-stranded DNA strands were added to one chamber and electrophoretically driven through the nanopore. This created a characteristic electrical signal that reflected the size and conformation of the DNA molecule. Graphene is thin enough to interact with individual nucleotides on a DNA strand as it passes through the nanopore, and therefore suitable for further development as a solid state DNA sequencing tool.

Graphene

Graphene is a single atom thick sheet of carbon – one layer of graphite. The carbon atoms are arranged in a hexagonal planar structure. Graphene has extremely high strength-to-weight ratio and has higher electrical conductivity than silicon. The material has been proposed as suitable for many future applications including a range of electronic nanodevices, batteries, touch screens, transmitters and receivers for broadband communications.

In 2010, the Nobel Prize for Physics was awarded to two scientists who made and discovered the properties of graphene, Professors Andre Geim and Konstantin Novoselov of the University of Manchester, UK. Institute of Physics briefing on graphene: www.iop.org/publications/iop/2011/