Rare Events

Automated Detection of Rare Cells

Fast and reliable detection of specifically labeled, rare objects on microscope slides.

The two main situations that take particular advantage of automatic slide scanning are rare event detection and statistical scoring of a large number of cells. The detection of fetal nucleated red blood cells (fNRBCs) in maternal blood presents an example of extremely rare events; another example would be the evaluation of circulating tumor cells (CTCs) for tumor staging and therapy monitoring. It is obvious that speed is essential in rare cell detection. The amazing speed of slide scanning achieved with the solutions by MetaSystems eliminates the need for enrichment steps with their inherent risk of losing cells of interest.

Fetal Cells

Isolating fetal nucleated red blood cells (fNRBCs) from the maternal blood facilitates prenatal genetic analysis without the need for diagnostic procedures that are invasive for the fetus. Such isolation usually involves specific antibody labeling and a technique for finding the extremely rare target cells in the sample. It could be shown that automated microscopy, the core skill of MetaSystems, is a feasible method for detecting fNRBCs. MetaSystems has developed elaborated software algorithms to make extremely fast, yet precise detection of rare events possible.

For the detection of rare fetal cells, thousands of cells are scanned per second. All detected objects are stored with their positions on the slide and a gallery image. The scanning system operated with the Metafer RCDetect module detects rare fetal cells based on their staining pattern. Scanning is performed in the primary signal channel. Specific staining patterns such as ring-shaped, membrane bound antibody staining are precisely identified. A second signal color channel can be used for confirming the detected object. Additionally, counter stain signals are used to distinguish the finding from extracellular debris.

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Circulating Tumor Cells

Circulating tumor cells (CTCs) are cells that have wandered off from a primary tumor into blood or the lymphatic system and are transported around the body in circulation. CTCs are believed to be the origin of additional tumors (metastases) in distant organs, causing the vast majority of cancer-related deaths. It is consensus that detection of CTCs may have important prognostic and therapeutic implications.

The ability of the Metafer RCDetect to detect rare events in fastest time makes it a perfect tool for finding CTCs. But the imaging software manages much more than localizing the cells. Each detected object is related to its position on the sample. Thus, a gallery of detected CTCs, for example, also resembles a position list for subsequent scans. It is therefore possible to relocate the tumor cells, and to perform further automated tasks such as FISH signal analysis. With this ability, the identified cells can be investigated thoroughly to gain additional information on their origin.

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Metafer BASE


The basis module Metafer BASE is a software for opening and reviewing Metafer data files, displaying measurement results, and manual confirmation of data.

Metafer SCAN


The Metafer SCAN module provides scanning functionality and serves as a basis for complete automated scanning systems. This includes the support of suitable scanning hardware (such as microscope, motorized stage, camera), the implementation of intelligent auto-focus algorithms, coordinate management, relocation function, and more. Includes Metafer BASE.

Metafer RELO


The basis module Metafer RELO is used to relocate objects according to their coordinates on the slide. Includes Metafer BASE.

Metafer RCDetect


The analysis module RCDetect is software for the detection of rare cells based on specific staining patterns. It uses a special algorithm that combines highest speeds with detection precision. Requires a Metafer basis module.

The list above is not exhaustive, and technical data may change. Please contact your MetaSystems representative for further explanations and details.


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.

Please contact us for further information.