Features

Author: David Baker

A research team at the University of Southampton has developed a technique for using Raman scattering an optical phenomenon for the rapid detection and identification of minute quantities of molecules in a sample of liquid. Gloucester Hospitals NHS Foundation Trust is conducting trials of the technique as a tool for making differential diagnosis of conjunctivitis from tear fluid.

When monochromatic light, such as from a laser, is focused on a sample, some light is transmitted, some absorbed and some scattered. Most of the scattered light has the same wavelength as the incident light this is known as Rayleigh scattering. A tiny fraction around one in 107 photons is scattered at different wavelengths, characteristic of the molecules contained in the sample.

This occurs because some of the incident light energy is absorbed by these molecules by the specific amounts that make them change their vibrational or rotational states. Known as Raman scattering, the radiation is thus unique in its spectrum for every type of molecule, so could potentially be used to detect chemicals within, or the chemical composition of, a given sample. As the intensity of the radiation is related to the number of molecules in a sample, qualitative analysis is possible too.

Raman scattering is extremely weak and difficult to detect. The Southampton team, however, has developed a method of amplifying Raman scattering using an electroplating technique. This involves the creation of a substrate with a gold coating containing an array of nanoscale cavities. The optical properties of these nanostructures concentrate light energy extremely efficiently, allowing the Raman effect to be enhanced by a factor of more than one million. This in turn paves the way for the detection of very weak concentrations of molecules in a sample.

A spin-off company from Southampton - Mesophotonics - manufactures the nanostructures under the name Klarite, and these are used with a Raman spectrometer. A small drop of fluid is placed on the chip and analysis by the spectrometer produces the characteristic 'fingerprints' of the molecules present, often in a matter of seconds. It is easy to see the potential benefits of being able to use a drop of tear fluid to make a quick, reliable diagnosis of ocular, and possibly systemic, diseases.

Differential diagnosis of conjunctivitis can be difficult - sometimes requiring the growing of cultures from swabs taken from the patient. This can take days in the laboratory, leading to significant delays in initiating the appropriate treatment. Given that bacterial or viral infections are associated with quite different changes in the chemical balance of ocular fluids, the Gloucester Hospitals team first built a database of measurements from more than 700 healthy and infected individuals, who also had their diagnosis confirmed by traditional laboratory testing. Raman spectroscopy was then used to record key components of changes in the chemical fingerprint of tear samples of these individuals, to be correlated with the traditional diagnoses.

Statistical processing could then group the fingerprint spectra into healthy, bacterial, viral and undetermined categories. Any new sample could then be matched to one of these classifications. Critically, the technique does not rely on knowledge of the underlying chemical changes or their precise cause, as it is the detection of complex changes in the balance of many chemicals that is reliably and quickly matched against the historical database. If the Gloucester trial is successful, there is an estimated saving of £471m over 10 years to be made from reduction in laboratory time, better targeting of drugs and fewer patient visits. There is also the possibility of diagnosing diseases such as hepatitis, HIV, diabetes and chlamydia from tear samples.

 Towards invisibility

 

A team working in the experimental solid state (EXSS) physics group at Imperial College has found a way to make normally opaque solid objects appear transparent. And the study of the physics behind the creation of this effect may have exciting implications for laser technology, quantum computing and data security.

The opacity and colour of an object is due to the wavelengths of light it absorbs and reflects. But the absorption of light by an object is not fundamentally related to any particular arrangement of atoms, and the team has discovered how to manipulate, and even 'switch off', this effect thus rendering solid objects invisible.

Changing how objects absorb light is done by manipulating the electrons of the atoms they are comprised of. It takes light of precisely the right wavelength to excite a given electron from a lower state into a higher state, the light energy being absorbed in the process. By controlling the electron energy states in an object, the wavelengths of light absorbed by that object can be controlled.

The EXSS team has achieved just this by building a semiconductor nanostructure crystal an 'artificial atom'. These crystals are, in effect, nanoscale boxes whose size and shape can be varied to alter the energy levels of the electrons contained within. The team then found that, by directing a powerful laser at the crystals, they could control the motion of the electrons in such a way that they no longer absorbed light. Thus the normally opaque crystals instantly became invisible when but only when the laser was switched on.

The invisibility effect relies on the quantum wave nature of electrons. According to quantum mechanics, if an electron has two possible paths to reach a given point, the waves corresponding to those paths destructively interfere giving the strange result that the electron never actually reaches that point. The interaction of the laser provides a second pathway for electrons to move between states so that the process of light absorbtion is cancelled out and the crystals become transparent.

In addition, the EXSS team has been able to show that, not only can absorption be set at zero (transparency), it can be made negative (light amplifiction). This has profound implications for the future of lasers. As Einstein showed, lasers require more than half of the electrons to be raised to the upper energy state before light is emitted. The need for such 'population inversion' in turn means that lasers have to have a large energy input before they can work. However, when the quantum wave nature of the electron is considered, the interference effect described above can produce so-called 'gain-without-inversion' - light amplification even when most of the electrons are in an unexcited state. The door is then opened to wider applications for lasers in such fields as optical computers, medical imaging and environmental monitoring where, due to the energy traditionally required to run lasers, overheating and power considerations can be limiting factors.

Quantum leaps

Another discovery related to the invisibility effect is that the speed of light is slowed by a factor of almost 40 inside the crystals on the appearance of optical gain. By passing such a light signal through a network, it may be possible to design new methods of storing and manipulating data optically, and to easily detect disturbances to the signal (ie compromised security).

A quantum computer can then be envisaged, in which calculations are made by using the quantum interference effects of electrons. The EXSS group estimates that such a computer, comprising just 1,000 of their crystal nanostructures, could perform in one second a calculation that would take a normal computer longer than the age of the known universe to perform.

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