Next Generation: Sneaking into a Cell

A nanoscale device measures electrical signals inside cells without causing damage.

By Megan Scudellari | 

A false color SEM image of the BIT-FET overlaid with an image of a cluster of cardiomyocyte cells, illustrating how intracellular action potentials are recorded by the device L. Robles, Opus design & X. Duan, C. M. Lieber, Harvard University

THE DEVICE: It is not easy to record the electrical signals that pass fleetingly through neurons and cardiomyocytes. But with a novel nanoscale device developed byCharles Lieber

 

 and colleagues at Harvard University, scientists can record these action potentials without damaging cells and even probe sub-cellular structures like dendrites, according to a report

 

 published last month (December 18) in Nature Nanotechnology.

The branched intracellular nanotube field-effect transistor, or BIT-FET, joins a nanowire and a nanotube into a slim T-shaped structure that can be inserted into a cell up to five times in the same place without disrupting the action potential or damaging the cell. The tiny hollow nanotube, 50-100 nanometers wide, penetrates the cell, sucking up a bit of the cytosol as it enters. This cytosol comes in contact with the nanowire outside the cell, and when a voltage is applied to the nanowire, it operates as a transistor and detects the electrical signals passing through the cell.

IMPORTANCE: The BIT-FET is so small that it can probe sub-cellular structures such as individual dendrites, the authors reported, which are difficult, if not impossible, to access with existing methods, and could provide insights into neuronal communication. In addition, two BIT-FETs can be inserted into the same cell, where they independently record the same action potential. “The results are likely to have an outstanding impact on understanding the signal transduction among cells,” Zhong Lin Wang

 

, a nanoscience researcher at the Georgia Institute of Technology who was not involved in the work, said in an email. “The work is a great example of integrating nanotechnology and cellular level biology.”

 

BIT-FET devices coupled to chicken cardiomyocyte cells X. Duan & C. M. Lieber, Harvard University

WHAT’S NEW: The commonly used “patch-clamp” technique to record action potentials relies on cumbersome glass pipettes that often damage the cells under examination. In August 2010, Lieber and colleagues announced

 

 a nanoscale probe, kinked like a bobby pin, that could penetrate a cell without causing too much harm. The BIT-FET improves on the nano-hairpin because it’s even smaller, said Xiaojie Duan

 

, a postdoc in Lieber’s lab who led the BIT-FET project. “It’s just one teeny tiny nanotube, so it doesn’t do any harm to the cell.” And because of its size and shape, the device could eventually be used in a high-density array so researchers can measure the action potentials of a whole network of cells at the same time. The BIT-FET is also robust: after use, it can simply be washed in water and used again, said Duan.

NEEDS IMPROVEMENT: To make the technology practical, the researchers will need to fabricate an array of devices to facilitate measurements of the inner potential of many cells, said Wang. The team also hopes to improve the signal-to-noise ratio of the device, which can degrade the data and is currently worse than that of glass micropipettes used in the patch-clamp technique, said Duan. Finally, the team is implementing a stimulation function to the device so that in addition to recording electrical activity, it can serve to activate cells as well, said Duan. “Every technology has the space to improve,” she added.

 

The intracellular action potential signal recorded by a BIT-FET X. Duan & C. M. Lieber, Harvard University

X. Duan, et al., “Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor,” Nature Nanotechnology, doi: 10.1038/nnano.2011.223

 

, 2012.

Source: The Scientist
http://the-scientist.com/2012/01/18/next-generation-sneaking-into-a-cell/

 

Posted by
Robert Karl Stonjek

Backing out of the Nanotunnel

Science Daily — In the world of biomolecules such as proteins and the hereditary nucleic acids DNA and RNA, three-dimensional structure determines function. Analysis of the passage of such molecules through nanopores offers a relatively new, but highly promising, technique for obtaining information about their spatial conformations. However, interactions between the test molecules and the proteins used as pores have so far hindered quantitative analysis of the behavior of even simply structured molecules within nanopores.

This problem must be solved before the technique can be routinely used for structure determination. In a project carried out under the auspices of the Cluster of Excellence "Nanosystems Initiative Munich" (NIM), researchers led by LMU physicist Professor Ulrich Gerland and Professor Friedrich Simmel (Technical University of Munich) have developed a new method that depends on the analysis of reverse translocation through asymmetric pores, which minimizes the interference caused by interactions with the pore material itself. This approach has enabled the team to construct a theoretical model that allows them to predict the translocation dynamics of nucleic acids that differ in their nucleotide sequences.

The nucleic acids RNA and DNA both belong to the class of molecules known chemically as polynucleotides. Both are made up of strings of four basic types of building blocks called nucleotides, which fall into two complementary pairs. In their single-stranded forms, DNA and RNA can fold into what are called secondary structures, as complementary nucleotides in the sequence pair up, forcing the intervening segments to form loops. If the single-stranded loop is very short, the secondary structure is referred to as a hairpin. As in the case of proteins, the secondary structures of nucleic acids influence their biochemical functions. The elucidation of the secondary structure of nucleic acid sequences is therefore of great interest.

"Nanopores are increasingly being employed to investigate the secondary structures of RNA and DNA," Gerland points out. "Passage through narrow nanopores causes the sequence to unfold, and the dynamics of translocation provide insights into the structural features of the molecules, without the need to modify them by adding a fluorescent label. The technique is relatively new, and its potential has not yet been fully explored." In the new study, he and his collaborators used a new experimental procedure, which allowed them to quantitatively describe the passage of simply structured polynucleotide sequences through nanopores, and develop a theoretical model that accounts for their findings. This level of understanding has not been achieved previously, because complicating factors such as interactions between the protein nanopore and the polynucleotide have had a significant influence on the measurements and made it difficult to predict the behavior of the test molecules.

Thanks to a clever change in experimental design, the impact of these factors has now been minimized. The trick is to perform the measurements on molecules as they translocate through the pore in reverse. First, the polynucleotide of interest is forced through the conical orifice from one side under the influence of an electrical potential. This causes its secondary structure to unfold and, as it emerges, the molecule refolds. An anchor at the end of the polynucleotide chain prevents it from passing completely through the pore onto the other side.

For the return journey the potential is reversed, so that the process of unfolding now begins at the narrow end of the pore, and at this point the analysis is initiated. "In contrast to the situation during forward translocation, no significant interactions appear to take place during the reverse trip," says Simmel. On the basis of their experimental measurements, the researchers went on to construct a theoretical model that enabled them to predict the translocation dynamics of various hairpin structures with the aid of thermodynamic calculations of so-called "free-energy landscapes."

"This model could in the future provide the foundation of a procedure for the elucidation of the secondary structures of complex polynucleotides," says Gerland.

Researchers Develop New Strategy to Deliver Chemotherapy to Prostate Cancer Cells

o by Biomechanism 

Ligand-nanoparticle components (in green) targeting and binding to cells. Photo: Brigham and Women's Hospital (BWH)

Honing chemotherapy delivery to cancer cells is a challenge for many researchers. Getting the cancer cells to take the chemotherapy “bait” is a greater challenge. But perhaps such a challenge has not been met with greater success than by the nanotechnology research team of Omid Farokhzad, MD, Brigham and Women’s Hospital (BWH) Department of Anesthesiology Perioperative and Pain Medicine and Research.

In their latest study with researchers from Massachusetts Institute of Technology (MIT) and Massachusetts General Hospital, the BWH team created a drug delivery system that is able to effectively deliver a tremendous amount of chemotherapeutic drugs to prostate cancer cells.

The study was electronically published in the January 3, 2012 issue of ACS Nano. Co

The process involved is akin to building and equipping a car with the finest features, adding a passenger (in this case the cancer drug), and sending it off to its destination (in this case the cancer cell).

To design the “vehicle,” researchers used a selection strategy developed by Farokhzad’s team that allowed them to essentially select for ligands (molecules that bind to the cell surface) that could specifically target prostate cancer cells. The researchers then attached nanoparticles containing chemotherapy, in this case docetaxel, to these hand-picked ligands.

To understand Farokhzad’s selection strategy, one must understand ligand behavior. While most ligands mainly have the ability to bind to cells, the strategy of Farokhzad and his colleagues allowed them to select specific ligands that were not only able to bind to prostate cancer cells, but also possessed two other important features: 1) they were smart enough to distinguish between cancer and non-cancer cells and 2) they were designed to be swallowed by cancer cells.

“Most ligands are engulfed by cells, but not efficiently,” said Farokhzad. “We designed one that is intended to be engulfed.”

Moreover, the ability for a ligand to intentionally be engulfed by a cell is crucial in drug delivery since it enables a significant amount of drug to enter the cancer cell, as opposed to remaining outside on the cell surface. This is a more effective method for cancer therapy.

Another important aspect of this drug delivery design is that these ligand-nanoparticle components are able to interact with multiple cancer markers (antigens) on the cell surface. Unlike other drug delivery systems, this makes it versatile and potentially more broadly applicable.

According to the study’s lead author, Zeyu Xiao, PhD, a researcher in the BWH Laboratory of Nanomedicine and Biomaterials, current strategies for targeting nanoparticles for cancer therapy rely on combining nanoparticles with ligands that can target well-known cancer markers. Such strategies can be difficult to execute since most cancer cells do not have identifiable cell surface markers to distinguish themselves from normal cells.

“In this study, we developed a unique strategy that enables the nanoparticles to specifically target and efficiently be engulfed into any desired types and sub-types of cancer cells, even if their cancer markers are unknown,” said Xiao. “Our strategy simplifies the development process of targeted nanoparticles and broadens their applications in cancer therapy.”

________________

This research was supported by the National Institutes of Health, the David Koch-Prostate Cancer Foundation, and the USA Department of Defense Prostate Cancer Research Program. 

The World’s First "Nano-Ear" Can Listen to the Songs of Bacteria

Hearing sounds smaller than any we've ever heard before

By Clay Dillow

The 'Nano-Ear' Courtesy: APS via Physics World

German researchers have turned an optical tweezer device into the world’s first “nano-ear”capable of detecting sounds six orders of magnitude below the threshold of human hearing. Using an optically trapped gold nanoparticle as their listening device, the team says they can now detect sounds made at the bacterial level or use their device to tune (or perhaps to test?) the minuscule MEMS machines of the future.

The nano-ear is pretty simple, considering that it relies on technology that has been laying around in the lab for decades now. Optical tweezers are laser devices that use light to trap or manipulate a small particle in a particular point in space by drawing the particle to the most intense point in the laser beam’s electric field. By trapping a gold nanoparticle in just such a optical trap and measuring the influence of various sound waves on that particle, the found that they can “listen” to very small vibrations.

That means sound analysis at extremely low levels. The gold nanoparticle itself is just 60 nanometers (that’s 60 billionths of a meter, or roughly a thousand times smaller than a human hair), which makes it pretty sensitive to very small forces. The researchers used both a “loud” source--a tungsten needle glued to a speaker that vibrates at roughly 300 Hz--and a second source made up of bunches of other gold nanoparticles heated by a second laser to vibrate at just 20 Hz.

The nano-ear could hear them both loud and clear. The sound waves nudge the trapped gold nanoparticle in the same direction that the waves are propagating, allowing for precise measurement of the sound itself based on the particle’s motion. Experiments showed the nano-ear could detect vibrations down to about -60 decibels--or six orders of magnitude lower than human hears can. That means the device could be used to identify microorganisms or processes at the microscopic level by their sound signatures, or to help design and tune microelectrical mechanical systems.

[Physics World]

Quick-Cooking Nanomaterials in Microwave to Make Tomorrow's Air Conditioners

Engineering researchers at Rensselaer Polytechnic Institute have developed a new method for creating advanced nanomaterials that could lead to highly efficient refrigerators and cooling systems requiring no refrigerants and no moving parts. The key ingredients for this innovation are a dash of nanoscale sulfur and a normal, everyday microwave oven. (Credit: Image courtesy of Rensselaer Polytechnic Institute)

Science Daily — Engineering researchers at Rensselaer Polytechnic Institute have developed a new method for creating advanced nanomaterials that could lead to highly efficient refrigerators and cooling systems requiring no refrigerants and no moving parts. The key ingredients for this innovation are a dash of nanoscale sulfur and a normal, everyday microwave oven.

Rensselaer Professor Ganpati Ramanath led the study, in collaboration with colleagues Theodorian Borca-Tasciuc and Richard W. Siegel.At the heart of these solid-state cooling systems are thermoelectric materials, which can convert electricity into a range of different temperatures -- from hot to cold. Thermoelectric refrigerators employing these principles have been available for more than 20 years, but they are still small and highly inefficient. This is largely because the materials used in current thermoelectric cooling devices are expensive and difficult to make in large quantities, and do not have the necessary combination of thermal and electrical properties. A new study, recently published in the journal Nature Materials, overcomes these challenges and opens the door to a new generation of high-performance, cost-effective solid state refrigeration and air conditioning.

Driving this research breakthrough is the idea of intentionally contaminating, or doping, nanostructured thermoelectric materials with barely-there amounts of sulfur. The doped materials are obtained by cooking the material and the dopant together for few minutes in a store-bought $40 microwave oven. The resulting powder is formed into pea-sized pellets by applying heat and pressure in a way that preserves the properties endowed by the nanostructuring and the doping. These pellets exhibit properties better than the hard-to-make thermoelectric materials currently available in the marketplace. Additionally, this new method for creating the doped pellets is much faster, easier, and cheaper than conventional methods of making thermoelectric materials.

"This is not a one-off discovery. Rather, we have developed and demonstrated a new way to create a whole new class of doped thermoelectric materials with superior properties," said Ramanath, a faculty member in the Department of Materials Science and Engineering at Rensselaer. "Our findings truly hold the potential to transform the technology landscape of refrigeration and make a real impact on our lives." 

Trying to engineer thermoelectric materials is somewhat like playing a game of "tug of war," Ramanath said. Researchers endeavor to control three separate properties of the material: electrical conductivity, thermal conductivity, and Seebeck coefficient. Manipulating one of these properties, however, necessarily affects the other two. This new study demonstrates a new way to minimize the interdependence of these three properties by combining doping and nanostructuring in well-known thermoelectric materials such as tellurides and selenides based on bismuth and antimony.

The goal of tweaking these three properties is to create a thermoelectric material with a high figure of merit, or ZT, which is a measure of how efficient the material is at converting heat to electricity. The new pea-sized pellets of nanomaterials developed by the Rensselaer team demonstrated a ZT of 1 to 1.1 at room temperature. Since such high values are obtained even without optimizing the process, the researchers are confident that higher ZT can be obtained with some smart engineering.

"It's really amazing as to how nanostructures seasoned with just a few atoms of sulfur can lead to such superior thermoelectric properties of the bulk material made from the nanostructures, and allows us to reap the benefits of nanostructuring on a macroscale," Ramanath said.

An important facet of the discovery is the ability to make both p-type (positive charge) and n-type (negative charge) thermoelectric nanomaterials with a high ZT. Up until now, researchers around the world have only been able to make large quantities of p-type materials with high ZT.

Additionally, the new study shows the Rensselaer research team can make batches of 10 to 15 grams (enough to make several pea-sized pellets) of the doped nanomaterial in two to three minutes with a microwave oven. Larger quantities can be produced using industrial-sized microwaves ovens.

"Our ability to scalably and inexpensively produce both p- and n-type materials with a high ZT paves the way to the fabrication of high-efficiency cooling devices, as well as solid-state thermoelectric devices for harvesting waste heat or solar heat into electricity," said Borca-Tasciuc, professor in the Department of Mechanical, Aerospace, and Nuclear Engineering at Rensselaer.

"This is a very exciting discovery because it combines the realization of novel and useful thermoelectric properties with a demonstrated processing route forward to industrial applications," said Siegel, the Robert W. Hunt Professor of Materials Science and Engineering at Rensselaer.

Rensselaer graduate student Rutvik J. Mehta carried out this work for his doctoral thesis. Mehta, Ramanath, and Borca-Tasciuc have filed a patent and formed a new company, ThermoAura Inc., to further develop and market the new thermoelectric materials technology. Mehta has since graduated and is now a post-doctoral associate at Rensselaer. He also serves as president of ThermoAura.

Beyond refrigerators and air conditioning, the researchers envision this technology could one day be used to cool computer chips.

Along with Ramanath,Borca-Tasciuc, Siegel, and Mehta, co-authors of the paper are Rensselaer graduate students Yanliang Zhang, Chinnathambi Karthik, and Binay Singh.

This research is funded by support from the National Science Foundation (NSF); IBM through the Rensselaer Nanotechnology Center; and the U.S. Department of Energy through the S³TEC Energy Frontiers Research Center at the Massachusetts Institute of Technology (MIT).

Can One Phone Save Nokia and Microsoft? Nokia Lumia 900 - first hands-on video

The Lumia 900 is Nokia's attempt to draw level with Apple and Google and also carries the hopes of Microsoft.

• BY TOM SIMONITE

Audio »

Battle plan: Nokia's CEO Steven Elop announces the Lumia 900 at CES in Las Vegas.
Technology Review

It's blue, plastic, and could decide the fate of two multibillion-dollar companies. 

The Lumia 900 was launched by Finnish phone company Nokia at the Consumer Electronics Show in Las Vegas today with surprisingly frank talk from the company's CEO about how both his company and Microsoft trail in the market for smart phones.

Steven Elop repeatedly drew on military metaphors to describe how he planned to assault the U.S. market. "Clearly there are strong contenders already on the field, [and] our strategy has been to establish a series of beachheads," he said, before unveiling the new handset, which comes in either black or cyan, and will be available on AT&T's 4G network in coming weeks. "From that beachhead, you will see us push forward," said Elop.

The warhorse leading that charge, the Lumia 900, is an LTE device with a polycarbonate plastic case. It has a 4.3-inch screen with an OLED display that Nokia nicknames "clear black" and uses a technology unique to the company to deliver truer blacks than most OLED displays, said Elop. The phone's camera offers a wider angle of view than most smart phones, said Nokia senior vice president Kevin Shields while demonstrating the device on stage. He also boasted about the camera's large aperture, which means it lets more light reach its sensor. "The front camera lets in as much light as the back camera on pretty much any other smart phone out there," said Shields. The price for the Lumia was not announced, but Elop claimed it would be "competitive."

Nokia's partner of just one year, Microsoft, has as much riding on the Lumia 900 as Nokia does, as underlined by the surprise appearance of Microsoft CEO Steve Ballmer on stage with Elop. He underlined the commitment of the two companies to one another, one that cynics might say is due to the fact that each has nowhere else to go.

At the time of the agreement between the two companies, Nokia found itself without a smart phone operating system able to punch its weight against those of Apple and Google. Microsoft had just reinvented its struggling mobile operating system but faced an uphill battle turning the heads of phone manufacturers, such as Samsung and HTC, that had enthusiastically embraced Google's Android operating system.

"We didn't sign a contract to work together until less than a year ago," said Ballmer. "To go from concept and discussion to real engineering partnership to delivery is fantastic." He went on to call the Lumia 900 an "incredibly important milestone" before acknowledging that Windows Phone is far from on par with its competitors. "There's a lot of room to grow in terms of selling Windows phones," said Ballmer. "This third ecosystem is really going to pay off for users, for developers, for operators, and I trust for our two companies." There are now more than 50,000 apps available for Windows Phone, said Ballmer. Apple currently states that there are more than 500,000 apps for the iPhone, while Google said in October that there are over 400,000 for Android phones.

Latest model: The Lumia 900.
Technology Review

Elop claimed that Windows Phone provided a genuine alternative to models pushed by Apple and Google's mobile operating systems, which share basic design features like the way apps appear as icons. "The product itself has to stand for something, it has to be differentiated," said Elop, praising the "live tiles" of Windows Phone. The tiles are both shortcuts to apps and also notification areas that can show things like Facebook activity and Twitter messages. That design is much more valuable, said Elop, than "yet another collection of static applications on a grid."

He conceded that Nokia would have to make efforts to communicate that to consumers more familiar with Apple and Google's offerings, saying that 2012 would see the company spend money on that. Such is Nokia's need to see Windows Phone charm consumers that Elop even said he welcomed competition from other companies launching phones with that operating system. "I'm happy that Samsung and others are introducing Windows devices, because our principal competition is other ecosystems," said Elop.

Asked whether Nokia would release tablet computers, perhaps based on Microsoft's forthcoming Windows 8, Elop said that it would depend on being able to offer something different from existing tablets. "You want to ensure differentiation, as we have for phones, with camera optics, design, and the operating system," he said. "If we believe we can bring differentiation to tablets, whatever it may be, then clearly, it's an opportunity for Nokia."

Nanotech Goes Big

At a small factory in Concord, New Hampshire, workers at the startup Nanocomp Technologies are turning carbon nanotubes into paper-thin sheets many meters long. The nanotubes, which are each just a few billionths of a meter wide, are among the strongest and most conductive materials known. For decades researchers have dreamed of using them to make super-efficient electrical transmission lines, suspension bridges that can span several kilometers, and even elevators that convey satellites into space. But while some companies have succeeded in making useful products by mixing nanotubes with resins to create composites, it's been difficult to make materials with properties that reflect those of the individual nanotubes. By making large sheets composed of nanotubes alone, Nanocomp has taken a big step in that direction.

The sheets are still not as strong or conductive as individual nanotubes, but they can provide a lighter replacement for copper and other conventional materials in some applications, including protective shielding for coaxial cables. Nanocomp's first customers are NASA, which has used nanotube sheets to shield a deep-space probe from radiation, and the U.S. military, which could use the sheets to reduce the weight of the electrical cables on unmanned drones by half, increasing flight times.

Nanotubes are made by feeding alcohol and a catalyst into a furnace at high temperatures and pressures. Nanocomp has fine-tuned the process to produce relatively long nanotubes that emerge from the furnace to form networks that can serve as the basis for sheets. Practical large-scale manufacturing is the critical first step to futuristic applications, says John Dorr, the company's vice president of business development. That will get nanotube products out of the lab and to the market at competitive prices.

Researchers discover a way to significantly reduce the production costs of fuel cells

 by Biomechanism 

A noble metal nanoparticle catalyst for fuel cells is prepared using atomic layer deposition. This ALD method for manufacturing fuel cells requires 60 per cent less of the costly catalyst than current methods. Photo credit: Adolfo Vera

This ALD method for manufacturing fuel cells requires 60 per cent less of the costly catalyst than current methods.

This is a significant discovery, because researchers have not been able to achieve savings of this magnitude before with materials that are commercially available, says Docent Tanja Kallio of Aalto University.

Fuel cells could replace polluting combustion engines that are presently in use. However, in a fuel cell, chemical processes must be sped up by using a catalyst. The high price of catalysts is one of the biggest hurdles to the wide adoption of fuel cells at the moment.

---

The most commonly used fuel cells cover anode with expensive noble metal powder which reacts well with the fuel. By using the Aalto University researchers’ ALD method, this cover can be much thinner and more even than before which lowers costs and increases quality.

With this study, researchers are developing better alcohol fuel cells using methanol or ethanol as their fuel. It is easier to handle and store alcohols than commonly used hydrogen. In alcohol fuel cells, it is also possible to use palladium as a catalyst. The most common catalyst for hydrogen fuel cells is platinum, which is twice as expensive as palladium. This means that alcohol fuel cells and palladium will bring a more economical product to the market.

Fuel cells can create electricity that produces very little or even no pollution. They are highly efficient, making more energy and requiring less fuel than other devices of equal size. They are also quiet and require low maintenance, because there are no moving parts.

In the future, when production costs can be lowered, fuel cells are expected to power electric vehicles and replace batteries, among other things. Despite their high price, fuel cells have already been used for a long time to produce energy in isolated environments, such as space crafts. These results are based on preliminary testing with fuel cell anodes using a palladium catalyst. Commercial production could start in 5-10 years.

_____________

This study was published in the Journal of Physical Chemistry C. The research has been funded by Aalto University’s MIDE research program and the Academy of Finland. Journal reference: Atomic Layer Deposition Preparation of Pd Nanoparticles on a Porous Carbon Support for Alcohol Oxidation. The Journal of Physical Chemistry C, 2011, 115, 23067. dx.doi.org/10.1021/jp2083659