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Imaging system probes cancer cell mystery

1st April 2013


Atop-of-the-range DeltaVision Core microscopy imaging system supplied by Preston-based Image Solutions (UK) (Imsol) is at the heart of efforts being made by a team of researchers to unravel the mystery of how human cells turn cancerous.

The imaging system, which is designed to increase the ability to look at more probes and samples over longer periods of time than any competitive solution, is being used at the Manchester Interdisciplinary Biocentre (MIB).

This flagship research institute within the University of Manchester houses more than 60 research groups which can draw on expertise in engineering, physical sciences, life sciences and medical sciences.

Imsol's DeltaVision Core is central to the activities of Dr Dean Jackson, a cancer biologist within MIB's life sciences section. He heads up a small group investigating the links between structure and function within mammalian cells.

In particular, the group is very interested in the regulation of cell division. Hence the need for an extremely powerful imaging solution that can handle both fixed and live cells.

According to Jackson the two key advantages of the DeltaVision Core system are the speed and sensitivity that it brings to the group's two main activities: live cell imaging and nuclear structure remodelling during differentiation (Fig. 1). In the first, the imaging system is used to monitor the dynamic behaviour and stability of the structural sub-units of the chromosomes known as DNA foci. "These contain up to a million DNA base pairs each, are probably modular, and change in structure and chromatin density as different nuclear functions are performed. However, they are very difficult to analyse and require imaging technologies with good speed, sensitivity and resolution," he said.

The second focus for the group involves the use of mouse and human cell models in an attempt to unravel the processes at work during cell differentiation.

Here, the cells are dispersed in a complex 3D matrix in which they proliferate and form 3D balls. These balls eventually polarise, the central cells dying by apoptosis, to form hollow structures about 250µm across known as acini.

By labelling these cells, the scientists can use the DeltaVision Core for highly-detailed multi-channel imaging of the changes to 3D structure during the 14-21 day development and differentiation phase.

"In both situations it is important to have a very uniform and low power light source that allows image capture without damaging the sample. The Xenon source on the DeltaVision with appropriate filters gives excellent illumination that is much less damaging than the equivalent laser illumination using confocal microscopy," he added.

Confocal microscopes

From Olympus, the FluoView series of laser scanning confocal microscopes offers a choice of several system configurations that are able to meet the needs of an individual researcher or a number of researchers with a variety of different applications.

For example, the Olympus FV1000 is a new generation imaging system for living cells and offers a host of advanced features that enable state-of-the-art research projects to be conducted with ease. The system incorporates two laser scanners in a single compact design for simultaneous excitation and observation.

It delivers all of the key performance functions required of a confocal laser scanning microscope, minimising specimen damage following rapid changes in living systems and accurately capturing a full range of information.

Intuitive interface

The FV300 is a point-scanning, point-detection, confocal laser scanning microscope designed for biology research applications. Olympus says that excellent resolution, efficiency of excitation, intuitive user interface and affordability are key characteristics of this instrument.

When configured with visible-excitation, the microscope permits simultaneous collection of up to three detection channels. Maximum optical efficiency is combined with easy, one-touch selection of pinholes and filters.

Discontinued with the introduction of the FV1000, the older FV500 is a fully automated confocal system that can be configured with ultraviolet through infrared lasers and permits simultaneous collection of up to five detection channels. Existing FV500 hardware is capable of being matched to either the IX2 inverted research microscope platform or the BX2 upright research microscope platform.

In terms of overall features and benefits, the FluoView system can improve conventional fluorescence images by recording fluorescence generated from the focal plane within the sample, while rejecting all other light coming from above or below the focal plane.

The efficient point-scan/pinhole-detection confocal optics of the FluoView systems virtually eliminate out of focus light to produce high-contrast images with superb resolution.

All three models are fully integrated workstations that incorporate user-friendly image acquisition and image analysis software with high-resolution confocal optics that require no user alignment.

An intuitive, Windows-based graphic user interface allows new users to quickly generate images in a wide variety of scanning modes.

Standard image formats, including the popular TIFF and AVI algorithms, permit easy, direct export of FluoView images to off-line analysis packages.

When it comes to scanning techniques, the microscopes provide innovative scanning techniques for improved performance.

Included in the palette are point, line, free line and rectangle scanning modes that make the FV300 or FV500 especially suitable for many time-lapse applications. Sequential scanning can also be performed in order to minimise crosstalk between fluorophore channels by exciting each dye individually, and then assembling the images into a final montage.

Auto focus

New from Applied Scientific Instrumentation (ASI) is the Bioquant Automated Imaging Toolkit plug-in which employs the company's MS-2000-XYZ motorised stage and auto-focus module to simplify diverse imaging tasks.

The plug-in provides time-lapse imaging of multi-welled plates and culture dishes, high speed slide documentation, and efficient user controlled motion across a slide.

The ASI MS-2000-XYZ stage is also used with the Bioquant Stereology Toolkit plug-in to Bioquant NOVA to provide superior closed-loop tracking of Z-axis position and dissector location.

In addition, the stage is tightly integrated with other Bioquant NOVA measurement features such as bone histomorphometry, cell counting, brain mapping, and 3D reconstruction.

PerkinElmer is promoting high content Analysis (HCA) and high content screening (HCS), imaging-based multi-parametric approaches of cell analysis at the single-cell level.

Originally developed as a complementary technology to traditional biochemical high-throughput screening (HTS) in drug discovery, today HCS is established in a far broader area of the life science space as an unbiased method of imaging multiple cellular samples.

The company says that both HCA and HCS offer a number of advantages over traditional techniques, including: more information from cellular samples because fully automated imaging and unbiased image analysis exploit the full potential of microscopy; more meaningful results as screening can be performed under physiological and biological more relevant conditions than in a classical biochemical scenario; and more questions answered simulatenously as the data-sets they provide are more information rich than biochemical read-outs.

Mini system

Finally Nanopoint has released a state-of-the-art digital USB mini-microscope system for use by middle and high school biology teachers to enhance existing cell biology education in today's schools.

The cellTRAY Mini-Microscope is a compact inverted digital imaging system that provides science teachers with a state-of-the-art teaching platform.

The system was designed to be easy to assemble and use with minimal preparation time and easy to transport with its durable travel case making it portable for sharing among multiple classrooms and teachers.

Its compact size makes the system easy to fit on a teacher's desk or lab table and the scientific grade digital camera and software makes it easy to capture high quality images.





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