Research highlight

Bright ideas to conquer new worlds

SFI Research Image Award 

Thanks to its precision, there is a new focus on the use of light to do everything from sending cancer-killing drugs to their target to finding new planets

LIGHT IS AN integral part of our lives – yet perhaps we take it a little for granted. Those educated in how to use its beams can elicit much more information than one might expect, whether they are diagnosing and treating cancer, trying to understand how cells work or seeking planets in other solar systems.

One scientist who is plugging into light is Malini Olivo, professor of biophotonics at NUI Galway’s school of physics. She recently moved to Ireland from Singapore, where she has been working for two decades on photomedicine, which involves the study and application of light in health and medicine.

At present, many standard procedures for examining hollow organs, such as the gut, lungs and bladder, involve inserting an endoscope and channelling white light in to look at the tissue. Olvio’s research takes that to the next level.

“Light in the visible range has been used particularly in looking at endoscopic applications,” she says. “But white light itself does not discriminate very well because you can’t see very good contrast on lesions that are flat.”

As many serious cancers form flat lesions, this is a problem, she notes. “Relying on visible white light alone is primitive at this point in time and yet it is standard practice.”

Instead she is using fluorescence to highlight cancer cells in endoscopy, (Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength.) This is done by targeting specially designed optical probes at cancers and causing them to light up, or by exciting aspects of the cancer cell’s own innate fluorescence, which is different from that of non-cancerous cells. The increased contrast can allow doctors to better detect cancers in the patient, explains Olivo.

“There are lots of novel ways of using light,” says Olvio. “Now with nanotechnology a lot of these optical probes can be very well constructed and delivered within very small nanoparticles. These can be easily targeted at specific biomarkers in the body.”

Other techniques being explored include picking up the signature of “Raman scatter” from cells when light is shone on them, and even using miniature confocal microscopes to non-invasively optically slice into tissue and view it in three dimensions. (Confocal microscopes increase optical resolution and contrast by using a spatial pinhole to eliminate out-of-focus light.)

Once a tumour has been detected, light could even play a role in treating it. Photodynamic therapy (PDT) targets drugs at tumours and literally switches them on with light, thereby causing the cells to die.

Olivo’s work in Singapore suggests that, if you treat a primary tumour this way, it can also fight other cells of that cancer in the body.

“We found out that PDT seems to be triggering a positive immune response to cause lesions that were not treated to respond,” she says of a case report published in The Lancet Oncology in 2007. “People had seen this in animals, but we were the first to report this in humans.”

Light is a powerful tool in lab-based research too, according to Prof Brian Harvey, who directs the National Biophotonics and Imaging Platform, Ireland. Light-based microscopes are becoming far more powerful, he says. “This has potential for drug discovery as the higher the affinity, the more likely it is to have an effect.”

Harvey’s work at the Royal College of Surgeons and Beaumont Hospital looks at cystic fibrosis. His team has developed a lab-based model of lung cells affected by the disease that they can watch closely, using fluorescent dyes to enhance the contrast as they observe fluid volume, which is an important factor in the condition.

“Because we need very precise measurements, down to a millionth of a metre, we have to use probes that give us high definition of boundaries. You can’t use normal light for that, the background noise is too high,” explains Harvey.

The scientists use laser light to make the probes fluoresce, then high-speed cameras allow them to monitor events, including the movement of fluids, over time scales of thousandths of a second. Testing the reaction of the cells to various compounds has led them to a potential agent that could help improve cell function, according to Harvey.

At the same time, the high-speed camera technology the biologists are using to capture events at the cell and molecular scale can also be applied to the other end of the size spectrum, in astronomy, explains astrophysicist Dr Niall Smith, head of research at Cork Institute of Technology and co-founder of Blackrock Castle Observatory.

“Essentially almost all the information we get about the universe around us comes from the light we detect,” he says.

Astronomers look for variations in the brightness of distant stars in other solar systems to try and identify when exoplanets – those outside our solar system – are circling them. “One way to detect exoplanets is to look for a very small dip in the light as the planet passes in front of a star,” explains Smith.

Taking those measurements from telescopes on earth can be difficult because the atmosphere gets in the way. (The factors that make stars appear to twinkle at night can also blur images.)

Techniques exist to correct for the aberrations, but Smith and his colleagues in Cork have come up with a new way of making the images better. This opens up the possibility of finding exoplanets using relatively inexpensive ground-based telescopes instead of big-ticket space observatories.

The approach, which was discovered by graduate student Adrian Collins, hinges on using more rapid exposures and high-speed cameras, then using an objective method to measure the relative brightness of stars in a frame and select the images that yield the most accurate information.

“By selecting the good ones, we can improve the precision of these measurements of brightness by 50 per cent,” says Smith. “And this is compared with data taken at professional observatories high above sea level with all the lovely skies they have there.”

For observations closer to sea level, which have more atmosphere to contend with, the technique can improve brightness measurements by as much as 70 per cent, he adds.

“It seems that, if you have a big telescope on the earth and you take very quick, short exposures, you can probably do as well measuring the brightness of things as you can from space,” says Smith. “If this is true, this would be a huge thing.”

A biochemical fingerprint of cancer 

LOOKING AT samples of cervical smears down a microscope to scan for cancer is standard practice. A group at the Dublin Institute of Technology is looking to add another string to that bow, however. “Normally, people look down the microscope and collect the image, ” says researcher Dr Fiona Lyng.

“They have a picture of the cell, but it’s very subjective, it doesn’t tell you quantitative information and it doesn’t tell you about the molecules.

“But we shine light on the cells and we collect the light that is scattered.”

It provides a biochemical fingerprint of the molecules in the cell and, by comparing the spectra to known references, it is possible to identify whether cancer is present.

“We can basically reduce considerably the number of false positives and negatives,” she says.

“So far in our tests, if we have a sample we can identify it with 98 per cent accuracy.”

The technology, Cervassist, has been supported by Dublin Institute of Technology’s Hothouse and Enterprise Ireland.

The group is now completing trials at the Coombe Hospital in Dublin and working with business partner Raman Diagnostics to complete development.

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