The idea behind this particular nanosensor came from study of natural biosensors within cells. All living things monitor their condition, from the largest scale of organs to the smallest nanoscale chemistry of individual cells. At the level of the cell, there are billions of specialized proteins or RNA that perform the task of a sensor by reacting to the presence of very specific molecules. For example there are many loops or cyclical chemical pathways, where a certain condition, say a need for energy, triggers a chemical and physical change in one sensor protein. It in turn signals for production of more energy. When enough energy is produced, another sensor protein accumulates to the point where it turns off energy production.

Scientists at the University of California, Santa Barbara (USA) and the University of Rome Tor Vergata wanted to emulate this natural sensor-signal process with a specific target in mind. As published in the Journal of the American Chemical Society [04 August 2011, paywalled, Transcription Factor Beacons for the Quantitative Detection of DNA Binding Activity] they developed a sensor made from DNA that becomes luminescent (glows) when it encounters a particular protein of the type called a transcription factor. These are proteins used by cells to control the production of molecules (usually other proteins). There are literally thousands of transcription factors, but when scientists ‘reprogram’ cells for example in stem cells; they often change only a handful of factors. The trick is to know whether the reprogramming has worked properly or not. That’s where the nanosensors come in.

There are many techniques for reading transcription factors; most of them require laborious separation of specific proteins and examination either under microscopes or with chemical detectors. As one of the researchers put it, “With the new sensors, we just mash the cells up, put the sensors in, and measure the level of fluorescence of the sample.”

The sensors are built by re-engineering three natural DNA sequences, each set to recognize a different transcription factor, by adding a molecular switch that becomes fluorescent when activated. Eventually this technique can be extended to thousands of transcription factors. In turn, the technique can help scientists and doctors monitor the level of drug activity, screen for certain kinds of cancer signaling proteins or any other application where transcription factors might reveal an underlying biological condition. In short, this technique could be very useful and practical.

The technique also seems relatively simple, but it will ultimately compete with many other technologies (sometimes called assay technology) that read the presence of transcription factors and other protein signaling molecules. It’s a burgeoning field of cell biology and of sensor technology-in-the-very-small.

The electricity is generated by the flexing of zinc oxide nanowires in what is called the piezoelectric effect. Zhong Lin Wang, a Regents professor in the School of Materials Science and Engineering and his team have been working on piezoelectric nanoscale devices for many years.

The technology for nanowires of zinc oxide is also not new, but Wang and team have focused on the manufacturing aspects – working to make the construction of the devices scalable (the ability to produce large numbers) and to coax more efficiency from the design. The latest advance comes from embedding the nanowire structure in a polymer substrate (essentially a plastic wafer). The wires then generate a current as they are compressed. Since they are completely enclosed in the polymer, they can be used in many different environments. The nanogenerators are produced in a multistep process that includes the important step of connecting electrodes to the nanowires. Two common connections, Ohmic (linear and symmetric current) and Shottky (non-linear and asymmetric current) are available. The wire arrays can be built both vertically and horizontally providing flexibility for manufacturing formats. Lateral nanogenerators integrating 700 rows of zinc oxide nanowires produced a peak voltage of 1.26 volts at a strain of 0.19 percent. In a separate nanogenerator, vertical integration of three layers of zinc oxide nanowire arrays produced a peak power density of 2.7 milliwatts per cubic centimeter. These are obviously producing minute amounts of electricity, but hooked to nanoscale sensors – the energy requirements are also minimal.

This is the sort of detail that can make or break the transition of nanotechnology to commercial production.

The new generator and nanoscale sensors open new possibilities for very small sensing devices that can operate without batteries, powered by mechanical energy harvested from the environment. Energy sources could include the motion of tides, sonic waves, mechanical vibration, the flapping of a flag in the wind, pressure from shoes of a hiker or the movement of clothing.

“Building devices that are small isn’t sufficient,” Wang noted. “We must also be able to power them in a sustainable way that allows them to be mobile. Using our new nanogenerator, we can put these devices into the environment where they can work independently and sustainably without requiring a battery.”

[Source: EurekAlert]

The innovation is the ability to align the nanotubes – like tiny standing strands of hair (however, only 1/100,000 the size of hair) – as the sensitivity element attached to a much larger (though still almost microscopic) MEMS (microelectromechanical system) device. The nanotubes are created in a methane atmosphere at high temperature, which creates small deformities in the crystalline structure of the tubes that have great sensitivity to movement – movement as small as a few atoms. The MEMS device is like a packaging to add the electronic inputs and outputs necessary to turn the sensitivity of the nanotubes into electronic signals. The complete package remains very small.

Another focus of the research was to make sure the nanotube/MEMS combination was easy to manufacture. This is often one of the stumbling blocks of nanotechnology. In fact, most previous nanosensors required hand-crafting techniques. This nanosensor can be manufactured with automatic systems and should be able to scale (ramp up production numbers) to meet the needs of a variety of industries.

The market for MEMS devices, which take mechanical signals and convert them into electrical impulses, is estimated to be worth billions. “The main challenge facing the industry today is to make these basic sensors a lot more sensitive, to recognize minute changes in motion and position. Obviously there is a huge interest from the military, which recognizes the navigation potential of such technologies, but there are also humanitarian and recreational uses that can come out of such military developments,” Prof. Hanein [Professor Yael Hanein, Engineering Faculty] stresses. More sensitive MEMS could play a role in guided surgery, for example.

[Source: Tel Aviv University]

The Tel Aviv University team is working on increasing the sensitivity of their current device.

It’s more than a disinfectant and hair bleach, that’s for sure. It’s an organic compound (H2O2) found in all organisms that use oxygen for metabolism. It has been known for some time that hydrogen peroxide can damage cells and DNA, but recently it’s also become known that it is used as a signaling molecule for the stimulation of cell growth. Signaling molecules are like messengers; they get sent when something needs to happen – in this case, the chemistry of cell metabolism comes to the point where cell growth or division is ‘necessary’ and it generates hydrogen peroxide molecules. These molecules, in turn, work with a common growth factor called EGF (Epidermal Growth Factor), which binds to its receptor on the outer membrane of cells (EGFR). This induces cells to grow or divide. In some way (still unknown) hydrogen peroxide amplifies the EGFR signal.

The hydrogen peroxide molecule is very small and typically does not leave the vicinity of a single cell – hence the need for detection at the level of one molecule and one cell.

The sensor constructed at MIT is a film of carbon nanotubes embedded in collagen (a gel-like protein that makes up about 20-35% of animal tissue). Cells are grown on the surface of this nanotube ‘carpet’ and the collagen attracts the hydrogen peroxide produced by the cells. To get to the collagen, however, the hydrogen peroxide must enter a nanotube. The nanotubes have been treated with a fluorescent material that reacts in the presence of hydrogen peroxide. The nanotubes ‘flicker’ when reacting, which can be recorded and counted – thus providing an accurate count of the production of hydrogen peroxide, one molecule at a time.

This has a variety of uses…

The team also found that in skin cancer cells, believed to have overactive EGFR activity, the hydrogen peroxide flux was 10 times greater than in normal cells. Because of that dramatic difference, Strano believes this technology could be useful in building diagnostic devices for some types of cancer.”You could envision a small handheld device, for example, which your doctor could point at some tissue in a minimally invasive manner and tell if this pathway is corrupted.”

Strano points out that this is the first time an array of sensors with single-molecule specificity has ever been demonstrated. He and his colleagues derived mathematically that such an array can distinguish “near field” molecular generation from that which takes place far from the sensor surface. “Arrays of this type have the ability to distinguish, for example, if single molecules are coming from an enzyme located on the cell surface, or from deep within the cell,” says Strano.

Strano’s team is also working on carbon nanotube sensors for other molecules. The team has already successfully tested sensors for nitric oxide and ATP (the molecule that carries energy within a cell). “The list of biomolecules that we can now detect very specifically and selectively is growing rapidly,” says Strano, who also points out that the ability to detect and count single molecules sets carbon nanotubes apart from many other nanosensor platforms.

[Source: EurekAlert]

At the moment, the single molecule sensor array is more of a laboratory tool. It will be useful in pursuing the role of hydrogen peroxide in cell growth, of course; but if the approach is easily manufactured, and adaptable to other molecules – then this will become part of the ever increasing range of sensor technology.