applications Microscopy
Seeing is believing
Digital holographic microscopy is at last coming onto the market. nadya anscombe finds out why commercialisation has taken so long and what the future holds for this ground- breaking technology
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igital holographic microscopy promises to revolutionise the way we see the microscopic world. This non- invasive technique, which uses lasers and CCD sensors to build a digital hologram of an object, can not only be used to view objects that could previously not be seen without staining, such as transparent cells, but can also give quantitative information about the object. For life scientists it means being able to investigate unstressed transparent cells in their physiological medium, without a contrast agent and with low light intensity. For materials scientists, digital holographic microscopy can give topographic information not available with other microscopy techniques and the fact that it is a single-shot technique means it is fast and unaffected by vibrations. With so many important advantages and unique selling points, you would expect a booming market and lots of competition. Not so. There are currently only a handful of companies that offer DHM equipment, with the two main players being small start-up companies – Swedish company Phase Holographic Imaging (PHI) and Swiss company Lyncée Tec. The story of how the digital holographic microscopy came to be developed is a classic
10 ElEctro optics l june 2011
tale of a good idea waiting for technology to catch up. The idea of holography was first published in the 1940s, with digital holography proposed in the 1960s, but the components required to make digital holographic microscopy a reality have only recently become available.
Sensors, driven by demand from the digital camera market, now have the required resolution and size; computing power, required to process the vast amounts of information needed to reconstruct a digital hologram, is now easily available; and laser diodes, required to illuminate the sample, are now at the right price and performance levels to be integrated into digital holographic microscopes. ‘The sensors we needed were not available in 2001 when we first investigated the idea of digital holographic microscopy,’ said Peter Egelberg, CEO of PHI. ‘But, thanks to the digital camera market, there has been accelerated development of these sensors and the DHM market will benefit.’ PHI is also benefiting from developments in other industries, because its product uses the types of lenses conventionally used in DVD players. ‘Our aim is to make a low-cost product, so we use off-the-shelf components wherever we can.’
PHI’s technology has already proved to be an invaluable tool to life scientists enabling them to see detail and processes that they were unable to see using conventional techniques. For example, at Lund University, researchers have used PHI’s equipment to look at how cancer cells divide. David Gisselsson and his colleagues investigated how cancer cells created from asymmetrical cell divisions behaved over longer time periods. They were particularly interested to find out if such divisions can actually produce surviving daughter cells, because this is a prerequisite for abnormal cell divisions to ever contribute to tumour growth. ‘We were able to show that daughter cells
from a certain type of abnormal cell division can actually survive long enough to divide again, indicating that they can have a role in cancer development by providing a mechanism for continuous rearrangement of the tumour genome,’ explains Gisselsson. ‘This is in contrast to previous studies showing that the majority of abnormal cell divisions create non-viable daughter cells. The holographic technique also allowed us to make a detailed model of what was actually going on in the cell divisions that did lead to viable daughter cells and this led us to the discovery of a new type
DHM technology enables life scientists to look at cells over a longer period of time and observe cells splitting using time-lapse imaging. Image courtesy of PHI
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