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Pharmaceutical industry adopts terahertz waves

03 Jun 2005

Studying drug coatings is just one use the pharmaceutical industry has found for terahertz radiation. John Paul Cerroti, vice-president of product development at Teraview, tells Jacqueline Hewett about its current research and potential markets for the technology.

UK-based firm Teraview professes to be the world's first company solely devoted to the commercial exploitation of terahertz (THz) radiation. Founded in April 2001 as a spin-off from Toshiba Research Europe, the firm has raised £10 m (€14.6 m) in venture-capital funding since its inception.

JH: What application areas is Teraview targeting?
JPC: We have three application groups: analytical, medical and security. The analytical group is primarily focused on the pharmaceutical industry and is producing spectrometers and imagers. The medical group is concentrating on identifying cancers, particularly skin cancers. This is at the preclinical stage and we have not yet started clinical trials. We are working with excised tissue just now and we can differentiate between healthy and cancerous areas.

The security group is studying the use of THz radiation in applications such as scanners at airports. In THz spectroscopy, the contrast mechanism is the refractive index. This means we can see things such as ceramic knives, which cannot be picked up by metal detectors or X-ray machines. We can also get a spectroscopic fingerprint of plastic explosives, so we can tell they are there and, generally, identify what kind they are.

These three distinct groups are at different commercialization stages. The most advanced in terms of products is the analytical group. We have a spectrometer and an imager on the market, and have just launched a versatile version of the spectrometer. We also have a number of systems in well known pharmaceutical companies.

The next-most-advanced is the security group, although we are still some way from selling commercial products. We are working in partnership with Smiths Detection and are at the proof-of-principle stage at the moment. Once this stage is completed, we will develop prototypes that can be tested in airports, for example. After that, there will be another iteration to take the product to final sale.

How is THz being used in the pharmaceutical industry?
A big issue in the pharmaceutical industry is polymorphism. This is where you have a particular chemical entity that can crystallize in many different ways. The trouble is that the different crystallized forms dissolve at different rates. These rate differences can be enormous - the rate ratio between one form and another being as much as 500:1.

The kinetics of a drug dissolving in the stomach determine the release of the drug and it is important to have close control of this. Although there are a number of different techniques to observe crystal form, almost all of them have problems under certain circumstances.

For example, Raman spectroscopy heats the sample, which can change a polymorphic state from one type to another. X-ray diffraction is a good technique, except when you get preferred orientation of the crystal. THz radiation seems to be immune to most of these problems because we are looking not so much at the vibration of the atoms, but at the vibrations between molecules.

Another THz radiation application is the imaging of drug coatings, which can be complicated and multilayered. A coating can be designed to dissolve at a specific rate to control the release of a drug. Making sure that the coating structure is right is crucial. Existing techniques require the tablet to be sliced, but using THz we can do 3D volumetric imaging.

We fire pulses into the tablet and see reflections when there is a refractive-index change between the different layers. We can also make spectroscopic measurements. We get the pulse back in the time domain, but can Fourier-transform it into the frequency domain and get a spectrum of different parts of the tablet. Nobody else can combine those two aspects as far as we are aware. We have done a lot of work on tablet coatings, homogeneity and integrity.

How do you generate THz radiation at present and are you looking at alternative technologies?
We use a Ti:sapphire laser producing sub-100 fs pulses at 80 MHz. The pulses hit a semiconductor target with an applied bias voltage that essentially acts like a synchrotron on a chip. When the pulse arrives, electrons move into the conduction band and accelerate under the influence of the field. The resulting broadband THz radiation is diffraction-limited and covers 40 GHz-4 THz.

We are running a number of research programmes, including one on quantum-cascade lasers (QCLs). The trouble is, QCLs are single wavelength and have to be tied to a specific application. They are unlikely to replace pulsed systems for broadband THz generation.

Do you plan to reduce the size and price of your products?
In the long term, yes. The instruments are currently the size of a photocopier and that will come down to a bench-top system. We are currently selling instruments at up to £500,000. The price will fall over the next 5-10 years, but is unlikely to change a great deal during the next three years.

We are largely controlled by the cost of the femtosecond laser. The market for these devices is relatively small, but over the 5-10 year timescale, prices will come down significantly. The usual economies of scale should kick in as we start selling 10 to 100 systems per year and this should bring the price of the laser down.

There is also increasing competition in the marketplace. A couple of years ago, there were one or two players making these ultrafast sources, but now there are at least five firms, so it is getting more competitive. We also expect laser-makers to move on to second-generation products, which will hopefully be cheaper.

What problems do you face in getting products to the market?
The biggest problem we have is the timescale of the decision-making [of a potential customer]. When you are selling instruments at £250,000-500,000, you don't get a decision in five minutes. You need to do a lot of trials with people and they need to be convinced of the business benefit to them.

It is typically 18-24 months between first starting to talk to someone and the order being placed. This is the biggest challenge. We are a venture-capital-funded company and venture capitalists want their money back in reasonably short periods of time. Creating new markets usually takes a lot of time, so we are trying to focus our efforts.

What are Teraview's plans for the future?
The intention is to carry on with the pharmaceutical industry for our main sales effort and branch out into new applications. We are looking at applications involving inter-molecular relations such as those found in liquid crystals, where their behaviour depends on the position of the molecules with respect to one another. Over the next few years, we will also be improving and bringing out second- and third-generation products.

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