BIOTECHNOLOGY 37


and advanced instrument that uses 3D structured illumination technology, developed by a team at the University of California San Francisco (UCSF): this doubles the spatial and axial resolution of a widefield light microscope.


Additionally, this system can deliver high temporal resolution data for the study of fast dynamics in widefield mode.


“Imaging is complex and scientists have many types of conflicting requirements, however here we are looking at very fast moving objects travelling at 1-2 microns/ second, which requires wide field microscopy,” added Davis.


Upright platform One DeltaVision Core has been modified to work with an upright Olympus platform microscope, rather than the usual inverted microscope. Samples can therefore be viewed from above.


“Tis makes a big difference to us because we can image RNA as it moves in axons of motor neurons. We have also made modifications to allow micro-injections from the stage plate in order to carry out neurophysiological experiments,” he said.


Te DeltaVision OMX, on the other hand, gives the Department the ability to image at speeds of up to 100 frames/second (fps) with excellent spatial resolution.


Real-time molecule movement Researchers can now watch molecules move in living cells, literally millisecond by millisecond, thanks to a new microscope developed by scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany.


By combining light-sheet microscopy and single molecule spectroscopy, the new microscope can record the fluorescence of every pixel within view, and take snapshots at intervals of less than one millisecond.


With it, scientists can watch and measure very fast processes, such as the way molecules diffuse, across a whole sample, even one containing several cells (Fig. 1). Tis is a considerable step up from previous techniques, based on confocal microscopy, in which researchers could only observe at most a few isolated spots in a sample at a time.


“It’s really visual biochemistry,” says Malte Wachsmuth, who developed the microscope at EMBL. “We can follow fluorescently-tagged molecules in whole live cells, in 3D, and see how their biochemical properties, like interaction rates and binding affinities, vary throughout the cell.”


Until now, chromatin – the combination of DNA, RNA and proteins that forms chromosomes – had been observed in two states: wound tightly together, with most


G


GE Healthcare buys Applied Precision


E Healthcare has bought cellular imaging firm Applied Precision to bolster its pharmaceutical and life science research technology portfolio.


Applied Precision develops and markets high- and super-resolution microscopy instruments, software, and data visualisation tools for studying live and fixed cell structure and behaviour. GE says the acquired products will complement its


own IN Cell Analyzer systems used for high-throughput sub-cellular analysis in cell biology research. The firm


of its DNA inaccessible to the cell’s gene-reading machinery, in which case it is called heterochromatin; or loosely packed and easily readable, called euchromatin. But when they used the new microscope to measure the interaction between chromatin and a protein called HP1-a, the EMBL scientists made an intriguing discovery.


“In some areas that look like euchromatin, HP1-a behaves as it would in the presence of heterochromatin,” says Michael Knop, now at the University of Heidelberg, Germany. “Tis suggests that chromatin may also exist in an intermediate state between hetero- and euchromatin, which was not observable before in living cells.”


By providing a tool to watch molecules that move very fast, the scientists believe this new microscope will help to investigate processes ranging from the role of growth hormones in cancer to the regulation of cell division and signalling and the patterning of tissue development in the embryo.


Stereo applications Meanwhile, with its TL3000 ST (brightfield), TL4000 BFDF (bright-/darkfield), TL4000 RC/ TL4000 RCI (Rottermann Contrast technology) and the new flat TL5000 Ergo (automatic, zoom dependent contrasting) transmitted- light bases, Leica Microsystems is introducing a series of bases specially designed for a variety of stereo and


plans to retain Applied Precision’s facility in Issaquah, Washington. “The worldwide resources of GE Healthcare will


allow us to significantly widen our reach into new markets and provide us with a stronger support network for our existing customers,” noted Joe Victor, Applied Precision’s ceo. In December 2010, Applied Precision unveiled a number of new products including enhancements to its DeltaVision line of microscopy imaging systems. The new DeltaVision OMX 3D super-resolution system is a fourth-generation system the firm claims provides an eight-fold improvement in volume resolution.


macroscope applications from documentation of single cells to screening of whole animals.


Te Leica TL3000 ST transmitted- light base is the all-rounder of the line. Its integrated, innovative halogen illumination system guarantees perfect conditions for viewing transmitted-light specimens.


Tanks to its modest power consumption, base and specimen warming has been reduced significantly.


Te Leica TL4000 BFDF darkfield base is suitable for observing stained amplitude specimens. With its rapid switching between bright and darkfield as well as its sensitive deflection mirror adjustment, the base is optimal for semi-transparent specimens such as embryos.


With their innovative Rottermann Contrast technology, the Leica TL4000 RC and TL4000 RCI transmitted-light bases permit refractive index variations to be displayed as differences in brightness. Tis relief effect provides a wealth of variations that allow the maximum amount of information to be obtained from any specimen.


Together with the automated Leica M205 A or M205 FA stereomicroscopes, a computer and the Leica Application Suite (LAS) or the Leica Application Suite Advanced Fluorescence (LAS AF), many steps of the workflow can


The OMX Blaze has been developed to enable


extremely fast 3D-SIM for live cell imaging and near- video rate 2D-SIM. The latest DeltaVision Elite high- resolution microscopy system has been developed with increased automation as well as the firm’s UltimateFocus hardware autofocus technology and multiline TIRF capabilities. Also launched was the Monet localisation microscopy system, which utilises Applied Precision’s mixed-model algorithm to localise the positions of fluorophores and determine molecular distribution. The firm claims that Monet overcomes a number of limitations associated with PALM and STORM techniques while providing 2D resolution down to 20nm.


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