Imaging of Metaphases

Metaphase Finding and Image Acquisition

Building imaging workflows in high-throughput laboratories.

Automation of metaphase finding and imaging is one of the most efficient ways for improving throughput and quality in classical cytogenetics. Several independent studies have shown that the use of automated imaging systems in cytogenetics not only increases case turnover rates, but also improves analysis quality. MetaSystems offers a modern and flexible imaging solution for routine applications which is based on automated metaphase finding, unattended image acquisition and sophisticated case and image data management. The slide scanning managed by the Metafer software with its open concept can be integrated either as a stand-alone workplace or as part of larger, network-based multi-user environments. In both cases, Neon, the case management dashboard of Metafer, maintains case data, tracks processing states of all cases, and exchanges case data with external sources.

The software programs Metafer and Ikaros can all be used as building bricks for a customized workspace that grows with demand. If an integrated system managed by Metafer is supplemented with the innovative slide frame exchanger SlideFeeder x80, and possibly with the bar code reader and the immersion oil dispenser, such an integrated system can be configured to run as a 24/7 imaging server. Connected analysis stations with the Ikaros or Metafer software access the image and case database through Neon, and analysis results are immediately fed back to the main server.

Metaphase Finding

The Metafer module Metafer Metaphase automatically finds metaphases on suitable samples. Due to user-trainable classifiers it is easily adaptable to all kinds of preparations and contrasting methods (Giemsa staining, fluorescence, and even phase contrast). Detected metaphases are automatically displayed in an overview gallery and can be relocated with just one mouse click. Coordinates are easily transferred to manual microscopes. The direct interface to workstations with Ikaros installed makes metaphase finding with Metafer Metaphase a powerful tool for convenient and fast chromosome analysis.

Easy adaptation and parameter optimization to different cell types and preparations is of crucial importance for making an automated scanning system useful for routine analysis. To facilitate this task, Metafer Metaphase provides sophisticated training and optimization routines. The metaphase gallery, generated in real time during the search, provides fast overview of detected objects. Metaphases are easily relocated by clicking on the respective gallery image to allow for detailed inspection under the microscope, or using the digital live image. With the mouse, metaphases can easily be selected for acquisition, or they can be rejected or deleted in the gallery. Alternatively, the search classifier can be trained to assign quality scores to the metaphases, allowing for automatically selecting a defined number of best metaphases.

Additional parameters such as the mitotic index (MI) are automatically obtained during the scan. Positions of all metaphases and nuclei are displayed, and metaphases can be selected interactively or automatically. If clonal samples are scanned, the Metafer Metaphase can even select a given number of objects per clone, and it assigns the clone number to the metaphase's metadata.

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Automated Image Acquisition

Automated acquisition of high-resolution metaphase images efficiently increases the degree of automation in routine metaphase analysis. Each scanning system operated by Metafer generates position lists, representing the location of all detected objects. These positions are automatically relocated, and images of the objects at the position are acquired based on classifier-defined parameters. Once acquired, images are immediately available to any connected workstation.

The way how the images are acquired can be highly customized. After metaphase finding, for instance, all detected objects can automatically be sorted by their quality score. Metafer Metaphase can acquire a pre-defined number of best metaphases. To provide a complete picture, however, some randomly selected metaphases can additionally be captured. Objects can be acquired as raw images, or they can be subject to image processing. Focus stacks are supported as well as up to 12 different color channels, for example to automatically acquire FISH or mFISH metaphases. Objects are automatically centered in the image, and if they are larger than one camera field it is possible to acquire more than one image per position.

The automated immersion oil dispenser (AutoOiler) eliminates any human interaction between metaphase finding and image acquisition. Thus, if the SlideFeeder x80 is installed, the integrated scanning system managed by Metafer can find and capture images from up to 800 slides without any need for supervision by a researcher. Therefore, the integrated scanning system can capture images through the nights and over weekends or holidays.

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Legal Note

MetaSystems software and system products are classified as in vitro diagnostic medical devices (IVD) in the European Union in accordance with In Vitro Diagnostics Regulation (EU) 2017/746 or In Vitro Diagnostic Medical Device Directive 98/79/EC, respectively, and carry the CE label unless otherwise indicated. Use all MetaSystems IVD products only within the scope of their intended purpose.

MetaSystems products are used in many countries worldwide. Depending on the regulations of the respective country or region, some products may not be used for clinical diagnostics.

Some hardware components supplied by other manufacturers are not included in MetaSystems IVD products and are therefore not IVD medical devices.

MetaSystems software provides, among other functions, features to assist users with image processing. These include, but are not limited to, the use of machine and deep learning algorithms for pattern recognition. The output generated in this process should be regarded as preliminary suggestions and, in any case, mandatorily requires review and assessment by trained experts.

MetaSystems offers Customization Packages for application workflows that have been successfully implemented for customer labs using standard Metafer platform functionality. It is expected that they can be implemented for other customer labs using similar workflows and slide preparation procedures. If a Customization Package is purchased, MetaSystems product specialists will - based on their experience from other similar application cases - support the customer lab in adapting the Metafer software configuration to their needs. The performance of the solution will depend on the quality of the customer slides and the expertise of the users, MetaSystems cannot specify or guarantee any performance parameters. The validation of the solution for clinical use is the sole responsibility of the customer lab.

Please contact us for further information.