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Looking at live cells in the laboratory – the image solutions

1st April 2013


Formed in 1993 by owner and MD Ian Corless, Image Solutions has carved a niche for itself as a consultancy capable of putting together the type of imaging packages demanded by cutting-edge researchers: particularly those who work with live cells.

Based in a new headquarters in Preston, north-west England, the six-strong company draws on advanced technologies supplied by companies such as Applied Precision, Diagnostic Instruments, IBM, BioView and Intracellular Imaging.

It’s how the company puts these technologies together that makes it different. “We are,” notes Corless, “a value added reseller.” Image Solutions provides the intelligent glue that makes it all work.

Investment

Last year, Image Solutions’ biggest customer was Cancer Research UK. Much of that organisation’s E1.4m investment was on the DeltaVision, Image Solutions’ flagship and best-selling product.

Manufactured by US company Applied Precision, DeltaVision utilises image restoration microscopy in order to yield very high spatial data, at multi-wavelength and in time. This instrument is required for the precise acquisition, analysis and presentation of cellular and sub-cellular fluorescence data that cannot be easily achieved in any other system. So successful has Image Solutions been with its UK and Ireland DeltaVision franchise that Applied Precision has now extended it to include France, the Iberian Peninsula and the Benelux countries.


Battling the big four

But how does a small company like this manage in the face of competition from the big four – Zeiss, Leica, Olympus and Nikon?

Corless explains: “The reason we have been successful is that the design of the DeltaVision is subtly different in a number of arenas. It uses a structured illumination method that prolongs the life of a live cell sample. This is better than the standard confocal microscopy which utilises lasers which can be phototoxic to live cells. Typically, live cells remain viable for about 50percent longer with CARV structured illumination than with conventional confocal microscopy. This is very important as many of our research customers are doing time-lapse work that might last a number of days. And this is very much a growth area with lots more scientists doing live cell experiments now.”

He also points out that because DeltaVision has the most spatially accurate stage and focus on the market, it can consistently take up to 35micron sections through the sample at high Z resolution, giving an in-focus, de-blurred at all points in the image, at all time frames. This can also be done at any or many points in the spectrum from the UV to the near IR.

Simple multi-dimension acquisition, coupled with the ability to easily integrate photo-kinetics and high-powered analysis may well explain why the company has sold nearly 40 DeltaVisions to data.

Corless believes that another advantage for his company is that the big four regard his market as niche rather than mainstream. Plus they are still making healthy profits: he believes that one of the companies sold E5.7m-worth of confocal microscopes in the UK market in March alone. “Of course, if you are dealing with thick samples you do need lasers to get the required penetration,” he admits. However, the DeltaVision finds more market penetration with the growth of the confocal base, which means this instrument is often complimentary to, rather than competitive with the standard confocal.

However, there’s far more to an Image Solutions than simply DeltaVision. Take Bioview, for example. This delivers an outstanding cell imaging technology platform and software package that combines morphological, immune-staining and fluorescence in situ hybridisation (FISH) information on the same cell. Automated, high resolution and full colour staining puts morphology, immuno-staining and FISH staining on equal footing, enabling physicians and researchers to efficiently and effectively improve the quality of patient treatment and care.

BioView offers a set of capabilities that enable scientists and medical institutions to identify rare cells and respond quickly to treatments and care (Fig.1). High-speed delivery, excellent accuracy and high-resolution true colour imaging, the BioView Duet scanning unit, combined with BioView’s very own remote software and preparation kit enables its customers to combine rare event detection and genetic analysis in one process.

For example, automated interphase FISH scanning speeds up the slow and labour intensive process of testing for chromosomal disorders. One such application uses FISH on uncultured amniocytes using chromosome-specific DNA probes. Between

80 and 95percent of all chromosomal disorders expected in the second trimester can be discovered within 24 hours if DNA probes specific for chromosomes 21, 18, 13, X, and Y are used.

Another technology in the portfolio is the BDCARVII Confocal Imager. This delivers high resolution CCD confocal imaging in an easy to use and cost effective optical package that fits on to existing microscopes (Fig.2).

High-speed multi-point confocal scanning, combined with high quantum efficiency CCD cameras, minimises photo bleaching and allows real-time imaging and recording at up to 100 frames per second.

A long life arc source coupled to the instrument via an alignment free light guide allows for full spectrum (360nm–700nm) confocal imaging of virtually any fluorescent probe.

CARVII is becoming another Image Solutions success story, with the company just winning an extended franchise to cover the Nordic countries.

As important as the imaging package is the support contract that is on offer. This typically costs DeltaVision customers,

for example, between E11500–13000 every year and runs for 3–5 years. For this, Image Solutions will be onsite to deal with any problem within 48 hours at the latest. As the company carries a stock of spares, problems can usually be resolved very quickly. Whatever the cause, however, the service contract covers all parts and labour. “Many of our customers demand this level of service contract now because the equipment is often bought with grants from organisations such as Cancer Research UK and Wellcome and they want their investments properly looked after.”

This point has also been highlighted in a new report from analysts Frost & Sullivan (F&S). This says that the medical imaging equipment services market in Europe earned E860m in 2004 and that it will grow to just under one billion Euros in 2011. F&S puts this down to healthcare administrators coming under increasing pressure to operate along the lines of financial accountability within strict budget allocations.

As a result, a full service agreement such as that offered by Image Solutions with its predetermined fees covering a stipulated level of service, appeals greatly to administrators.

Corless believes that the service contract works to everybody's benefit – keeping the equipment in the best possible condition extends its life and reduces the likelihood of a major failure. Many instruments have to be run nearly continuously in order to satisfy the demand – so having the assurance that this will be possible is important to many of the company’s customer base.

“We’ll never be the least expensive,” he admits, “but we do what we say we’ll do. It’s a small pool of users really, so word would get round very quickly if we weren’t doing things properly. Besides, our staff have backgrounds in digital imaging which is quite a different thing from being very good at driving a microscope.”

Two to watch out for

Nothing stands still for long in the imaging world and Corless thinks that two advances in particular will dominate the rest of 2006 and into 2007.

The first is the electron multiplying charge coupled device (EMCCD). This major advance in camera technology has coincided with changes to how the CCD chips themselves are manufactured.

“You get hugely improved gain, which means that cameras can be used in very low light. This in turn reduces the amount of energy put into living cells and so further increases their life. It's literally gain without pain,” he said.

In the perfect world, every scientist using fluorescence microscopy wants a black background and readily identifiable markers in the foreground. Corless says you will now be able to get this because of EMCCD’s remarkable signal to noise ratio. He believes that up to 80 per cent of the DeltaVision users will want to upgrade and with each one costing E57000 it gives you an idea of how good this technology must be.

The other item to watch is how we go about visualising these huge datasets being generated by modern imaging techniques. He points to Imaris technology which makes tremendous use of graphic cards and SeeReal technology which gives 3D images so good that you feel you can touch them.

“There is a huge amount of research now into co-localisation in which scientists are trying to understand if and how one part of the cell influences another. These new imaging technologies, particularly in 3D, coupled with more processing power will give us dramatic clues about this.”

For more see www.imsol.co.uk





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