The novel nanosensors could be tailor-made to instantly detect the presence of particular molecules, for example poisons or proteins in patients' blood samples, with high sensitivity.
The researchers were led by Imperial College London physicists funded by the Engineering and Physical Sciences Research Council. The team showed that by putting together two specific nanostructures made of gold or silver, they can make an early prototype device which, once optimised, should exhibit a highly sensitive ability to detect particular chemicals in the immediate surroundings.
The nanostructures are each about 500 times smaller than the width of a human hair. One is shaped like a flat circular disk while the other looks like a doughnut with a hole in the middle. When brought together they interact with light very differently to the way they behave on their own. The scientists have observed that when they are paired up they scatter some specific colours within white light much less, leading to an increased amount of light passing through the structure undisturbed.
This is distinctly different to how both structures scatter light separately. This decrease in the interaction with light is in turn affected by the composition of molecules in close proximity to the structures. The researchers hope that this effect can be harnessed to produce sensor devices.
Lead researcher on the project is professor Stefan Maier from Imperial's department of physics, who is also an associate of Imperial's Institute for Security Science and Technology. He said: "Pairing up these structures has a unique effect on the way they scatter light - an effect which could be very useful if, as our computer simulations suggest, it is extremely sensitive to changes in surrounding environment. With further testing we hope to show that it is possible to harness this property to make a highly sensitive nanosensor."
Metal nanostructures have been used as sensors before, as they interact very strongly with light due to so-called localised plasmon resonances. But this is the first time a pair with such a carefully tailored interaction with light has been created.
The device could be tailored to detect different chemicals by decorating the nanostructure surface with specific 'molecular traps' that bind the chosen target molecules. Once bound, the target molecules would change the colours that the device absorbs and scatters, alerting the sensor to their presence.
The team's next step is to test whether the pair of nanostructures can detect chosen substances in lab experiments.
Professor Maier concludes: "This study is a beautiful example of how concepts from different areas of physics fertilise each other."
Meanwhile, the German Federal Ministry of Education and Research (BMBF) has just approved a joint project under leadership of Forschungszentrum Dresden-Rossendorf (FZD) and in collaboration with the University of Rostock, Proaqua in Mainz and the Helmholtz Centre for Environmental Research (UFZ).
The project is part of the Bionic Innovations for Sustainable Products and Technologies (BIONA) research programme. It will use the natural nanostructures of bacterial coat proteins to fix aptamers onto sensor surfaces in a controlled manner.
The UFZ is to develop aptamers that are capable of detecting certain organic substances, such as undesirable pharmaceutical residues, that enter the environment through wastewater (Fig. 1).
The term aptamer means something like "fitting pieces" (from the Latin word aptus, meaning to fit, and the Greek word meros, meaning piece). Aptamers consist of nucleic acids and have a 3D structure that enables them to identify and bind certain target molecules. These binding abilities allow, for instance, tracing, detecting and measuring certain substances. Hence their potential as biosensors.
The challenge is to identify the right aptamer for a particular target molecule. Such target molecules can be very complex structures, like whole cells or organisms, or tiny molecules consisting of just a few atoms.
This selection method is called systematic evolution of ligands by exponential enrichment (SELEX).
Scientists at the UFZ's biosensor laboratory have developed two different modifications of the SELEX method. One of these is known as FluMag SELEX. The 'Flu' stands for fluorescence and refers to the fact that a fluorescence molecule is added to the nucleic acids during the SELEX procedure to make them visible. In this manner the molecules can always be found again and researchers can measure the enrichment of those which exhibit best binding and detecting abilities to the given target. The 'Mag' refers to magnetic beads. These are dust-mote-sized magnetic beads onto which the scientists stick the even smaller target molecules to make them more manageable
Novel naval assays
Naval Research Laboratory scientists in the US are also partnering with industry to develop a sensor system for biomolecules that could make a significant contribution to a variety of fields such as healthcare, veterinary diagnostics, food safety, environmental testing, and national security.
NRL has developed a highly sensitive, portable biosensor system called the compact bead array sensor system (cBASS). This innovative instrument utilises a special integrated sensor chip, called the Bead ARray Counter (BARC), which contains an embedded array of giant magnetoresistive sensors. With 64200 µm diameter sensors on the chip, BARC has the potential to detect 64 different target analytes (Fig. 2).
The technology has already been licensed to Seahawk Biosystems Corporation in Rockville, Maryland, for further development in veterinary diagnostic, clinical diagnostic, and environmental applications.
Researchers at NRL began working on the magnetoelectronic biosensor concept more than a decade ago, under the leadership of Richard Colton and former NRL researcher David Baselt.
Baselt used a quantum-mechanical effect called giant magnetoresistance (GMR). In simplistic terms, GMR materials are magnetic field-dependent resistors - their resistance changes when subjected to an externally applied magnetic field. GMR devices are typically constructed of alternating magnetic and non-magnetic metal thin-film multilayers that are only nanometers in thickness.
Baselt looked specifically at a type of GMR called multilayer GMR in which the resistance of two thin antiferromagnetically exchange-coupled layers, separated by a thin non-magnetic conducting layer, can be altered by changing the moments of the ferromagnetic layers from anti-parallel to parallel. This change decreases the spin-dependent interfacial scattering of charge carriers resulting in a decrease in the resistance of the GMR material.
He realised this very sensitive phenomenon could have potential in the development of sensors for biological materials which are naturally biochemically specific, but are not usually magnetic. By attaching tiny paramagnetic particles to biomolecules, such as proteins or single-stranded DNA, scientists could then perform standard sandwich-type immuno or nucleic acid hybridization assays over the GMR sensors. The GMR sensors, each covered with complementary protein or single-stranded DNA (the probe), could then detect the magnetically labelled biomolecules (the target) the assays were designed to identify.
In a second development, NRL researchers have developed what they describe as a forceful new method to sensitively detect proteins. The researchers report the detection of toxins with unprecedented speed, sensitivity, and simplicity. The approach can sense as few as a few hundred molecules in a drop of blood in less than ten minutes, with only four simple steps from sample to answer.
The sensitive new test builds on NRL's patent-pending fluidic force discrimination (FFD) assay. In a FFD assay, a chip has arrays of receptor molecules such as antibodies that capture toxins or other target molecules that have been labelled with micrometre-sized beads.
By encapsulating the chip in a microflow chamber, the fluid flow can be controlled to apply just enough force to remove beads that are resting on the array but not truly labelling a toxin. "In this way," explains lead author Shawn Mulvaney, "very few molecules can be detected, because there is almost no background signal. And because we can get the background so low, FFD assays are very specific, with very few false positives."
The NRL researchers have adapted FFD assays to detect a protein toxin at concentrations as low as 35 attomolar - over 1000 times more sensitive than existing commercial tests for proteins.
In the new assay, dubbed 'semi-homogeneous fluidic force discrimination,' the antibody-coated microbeads are mixed directly with the sample and rapidly collect the dilute toxin molecules. The toxin-coated beads are then injected into the microflow chamber where they are captured by the receptor designed for that target. Finally, beads that don't belong are removed with fluid forces.
The remaining beads are all attached by the toxin to the surface and may be counted to indicate the toxin concentration. NRL has developed both electronic and optical systems to count the beads, along with reusable plastic test cartridges.
