Metafer RCDetect Rare Cell Detection System

General

The detection of rarely occurring cells inside a large population of 'normal' cells, i.e. the quantification of residual tumor cells in the blood or the bone marrow of cancer patients, has become an enormously important task in cancer or prenatal diagnostics, tumor staging and therapy monitoring. It requires a detection system of high sensitivity as well as reproducible specificity. Verification of the genetic pattern or expression status of the positive cells is indispensable for the low frequencies of cells (down to 1 cell in 10⁸) that need to be quantitatively assessed.

Metafer RCDetect Options and Links
RCDetect is fast and has clear advantages against FACS.	more...
The AutoCapt module is an option for RCDetect.	more...
The Isis FISH imaging system can be seamlessly integrated.	more...
The slide feeder extends the capacity of Metafer RCDetect to 80 slides.	more...

Detection of Rare Cells

The Metafer RCDetect rare cell detection system is a high throughput scanning system that automatically identifies immuno-fluorescently or immuno-histochemically labelled rare cells. Metafer RCDetect finds and records the cells performing a multiple-level object analysis, while quantitative occurrence rates are calculated by assessing the total number of cells within the scanning area during the scan. Intensity as well as shape recognition of both cell labels and counterstain assure high specificity. Staining artifacts and unspecifically labeled cell populations can be automatically rejected. The unique training feature allows for automatic adaptation to different labelling techniques or cell types.

RCDetect has distinct advantages over methods like RT-PCR or FACS, as the cell morphology is completely preserved. Fluorescent anti-body labelling can be followed by FISH assays without compromising hybridization quality. Positive cells are automatically relocated at high magnification to reject false positives, to verify the transformed status of the immuno-positive cells by their genotype or to detect unbalanced genomes. Studies have shown that the sensitivity is only limited by the absolute number of cells within the sample and that the specificity reaches 100% (Méhes et al., 2000).

All this functionality comes at an amazing speed of up to 7000 cells per second. Cells as rare as 1 in 10 million can now be detected, opening up totally new perspectives in applications like minimal residual disease or fetal cell detection in maternal blood.

AutoCapt: Automatic Capture of High Magnification Images

The automated image acquisition software AutoCapt captures high magnification (i.e., 63x or 100x) images from cells detected by RCDetect. It uses the position list which was generated by RCDetect to relocate the cells, automatically centres and focusses the images and stores them ínto the RCDetect data file. Images may be captured in the transmitted light  and in fluorescence mode, the latter with up to six color channels. Like all Metafer applications, AutoCapt uses classifiers to adjust the way, how the images are captured. Once the images are generated, they can be exported into various file formats like TIFF, JPEG or BMP. Hereby it is possible to export all images at the same time, or to select subsets or even single images to be exported.
For networked installations, with Isis FISH imaging workstations connected to the RCDetect system, it is even possible to let AutoCapt export its images into the proprietary file formats of these softwares. Images generated in this way may be easily opened on any external Isis workstation for further analysis.

AutoCapt is an option for Metafer RCDetect.

Integration of FISH Imaging

The Isis FISH imaging system seamlessly integrate into the RCDetect system, and can be used to acquire high magnification, high quality images of the detected cells or nuclei. Of course Isis is capable to capture various focus planes and to generate extended focus images. Since all MetaSystems products are based on a modular architecture, many different installations are conceivable:

• As a basic solution Isis may be installed on the Metafer system amd launched directly clicking a button in RCDetect. With this configuration Metafer transfers data like case name, slide designation and coordinates into the FISH imaging software. Isis may also be integrated as capture module, while the image preparation is done on external workstations.
• If the RCDetect system is too busy to allow the use of Isis on the same station, the RCDetect data may be opened on external relocation system (Relosys). Relosys workstations are equipped with a single slide motorized stage and provide a similar screen like the RCDetect system itself. Like in Metacyte, cells may be relocated and subsequently captured and analyzed in Isis.
• If RCDetect is extended with the AutoCapt software, Isis images may also be generated automatically. External workstations with access to the Metafer system amy then load the images for further analysis.
• If there is no network connection between the Metafer system and the Isis workstations, the coordinates may also be converted to the coordinates of each microscope. Relocation can then be done manually using the microscope rulers.

However the final network will look like: all MetaSystems installations will be tailored to the needs of the user, and all products work seamlessly together.