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New insights into the molecular level of cells

Correct diagnosis demands maximum quality and reproducible results, which is why scrupulously accurate measurement is a must in the laboratory. Innovative progress in technology opens up new insights into the molecular level of cells. New opportunities for successful treatment.
The market for cellular and molecular diagnostics is surging ahead. Suppliers on the international stage all want a bigger slice of the pie and are stepping up their commitment to European business with new product lines. Last year, the US company Cepheid made its European debut with its Genexpert product family for molecular testing systems and recently BD Diagnostics announced the European market launch of the open molecular testing system BD Max. Abbott Diagnostics is also wedded to the automation of molecular laboratory analyses and integrates sample preparation into the automation concept of its home-grown ‘mSystem’. 

Cell-based examinations not only of tumour disorders but also of infections and substance testing procedures of all types present laboratory analysis with new challenges. For example, an important area is immunostaining or antibody staining in order to render visible certain cell molecules in tissue. The Leica Bond-III stainer, a new development by Leica Microsystems, can process three completely separate sample slides for each of ten object carriers. The stainer can take up to 36 reagents and process tissue samples using different detection procedures in parallel for immunohistochemistry (IHC) and in situ hybridisation (ISH). IHC and ISH are analysis methods which are used mainly for the diagnosis of cancerous and infectious diseases. 

Becoming faster and cutting costs
The principal advantage of the automation concept with three robotic arms for sample handling is its greater processing speed. The manufacturer’s information states that the Bond stainer is 50% faster than older models without compromising on the quality of results. Both the parallel operation and the reworked software shorten the duration of test runs, something which increases throughput and therefore laboratory efficiency. Thanks to these advances, laboratories can deliver significant results faster and at lower costs.
The stainer is designed for Lean Histology and enables laboratories to increase their throughputs without needing to engage extra staff. Shorter throughput times release staff for other tasks and make it possible to run additional tests in the same time. The Leica Bonder was produced in collaboration with the company’s development partner Invetech.
Materials investigators in the pharmaceuticals industry are not alone in having their ears to the ground as regards cell-based assays. 

The microscopy department at Carl Zeiss is also paying close attention to new systems because obtaining good microscopic images, and especially depicting living cells in real time requires the broad experience and expertise of microscopy specialists. In order to produce high-resolution observation instruments for ever smaller dimensions, the boffins at Zeiss have come up with some ingenious ideas. For example, combining photo and electron microscope images. These two procedures have not yet been combined in one machine given that the physical properties of light and electron rays are quite different. However, the gateway to cross-system sample microscopy has already been opened up by Zeiss developers using a common interface for the sample and image transfer.
200 nanometres is the threshold value for the resolution of light and laser scanning microscopes. This enables observation of the penetration into a host cell of larger viruses marked with a fluorescent stain. To date, the only way that a molecular medical practitioner interested in the docking stations of viruses on cell surfaces can see images of the process is to use a higher resolution electron microscope. The specialist scrutinises his monitor for the fluorescence signals and overlaps both sets of image information and in this way can tell whether and where a virus is docking on to a cell or to what extent it has already penetrated. The physical limits of photomicroscopy are being extended by a new development from Carl Zeiss MicroImaging. The ELYRA PS.1 microscope system installed at the Reference and Translation Centre for Cardiac Stem Cell Therapy (RTC) at the University of Rostock can observe and document cell processes at molecular level in living cells. So far, rendering visible structures up to the ten nanometre level has only been possible with electron microscopes, although this procedure destroys living cells.
The microscope intended as an off-the-shelf model is the flagship among the new super resolution photomicroscopes and is designed for diagnostic investigations at molecular level and for the use of genetic engineering methods and nanotechnology on stem cells. The special twist in this technology platform is the integration of two different procedures – Superresolution Structured Illumination Microscopy (SR-SIM) and Photoactivated Localisation Microscopy (PALM), which deliver resolutions so far unheard of in conventional fluorescence microscopy.
The result is one to be proud of – structured illumination not only delivers a spatial image of the most minute structures but also with double the resolutions compared with conventional fluorescence microscopes and yet all the usual fluorescence stains can still be used. With PALM (Photoactivated Localisation Microscopy) switchable fluorescent proteins deliver degrees of localisation accuracy of up to 20 nanometres and less.
As an inkling of the surprises in store for molecular diagnostics, genome analysis and the Next Generation Sequencer are good examples. Originally restricted to the narrow field of DNA analysis, ultrasonic sequencers are now moving forward into other application fields. The furious rate of development and technological progress inspire cancer researchers just as much as they do immunologists. The current search for genetic mutations in cancer disorders is already discovering unknown disease focuses, in connection with leukaemia for example. Doctors use individual markers to discover disordered cells and can use the information thus gained to determine the appropriate therapeutic action.  
Andreas Beuthner 

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German Summary
Die Zell- und Molekulardiagnostik ist ein aufstrebender Markt. Internationale Anbieter wollen sich mehr vom Kuchen holen und verstärken ihr europäisches Engagement mit neuen Produktlinien.
Zell-basierte Untersuchungen von Tumorerkrankungen aber auch von Infektionen und Substanztestungen aller Art stellen die Laboranalytik vor neue Herausforderungen. Ein wichtiger Bereich sind beispielsweise die Immun- oder Antikörperfärbung um bestimmte Zellmoleküle im Gewebe sichtbar zu machen. Der deutschsprachige Beitrag ist nachzulesen auf www.meditec-international.com/medi0611lab