Metafer Slide Scanning Platform

Scanning and Imaging Fast, Modular Platform and Versatile METAFER SLIDE SCANNING PLATFORM

Metafer, MetaSystems' slide scanning fiers, the system is operated with just a platform, offers a unique combination of few mouse clicks. If a higher degree of selected scanning hardware and out- automation is required, Metafer can standing imaging software, resulting in even be operated completely unat- the most versatile and robust system tended with workflow files generated available for microscope imaging auto- by external databases. mation. Fast Versatile Metafer's performance is unsurpassed. Metafer software is unique in its archi- The slide scanning platform combines tecture. Based on a core of highly spe- state-of-the-art camera technologies cialized scanning algorithms, all auto- with optimized microscope configura- mated microscopy jobs are defined by tions, many different illumination sets of parameters bundled up in user- devices, and ultra-precise scanning accessible classifiers. Classifiers con- hardware to achieve unrivaled scan- tain information on hardware and ning speed and precision. The software settings, protocols for intelli- renowned MetaSystems CoolCube g e n t a n d a d a p t i v e a u t o f o c u s series is a complete line of high- sequences, image processing macros, resolution and ultrahigh-resolution and also the object features to analyze. CCD and CMOS cameras. All cameras Metafer systems can host a virtually are available as b/w or color models. unlimited number of classifiers. This For illumination, Metafer users can concept allows for applying the same choose from a variety of devices includ- Metafer platform to many different ing white LED lamps and multicolor LED assays. Despite this versatility, Metafer light sources. All pieces of Metafer software is also very easy to use rou- hardware have been thoroughly tested tinely. Once a workflow has been and were selected based on their out- defined by creating one or more classi- standing performance. Metafer Highlights a Open Platform Architecture Flexible scanning configura- tion, customizable workflow design, and transparent results documentation with many import and export possibilities a High-Speed System Optimized algorithms, high- resolution cameras, and modern scanning hardware for highest scanning speed a Optimized for Clinical Routine Seamless integration in different working environments, and one-click or remote operation (e.g., by data from LIMS) a Intelligent Focusing Elaborate autofocus algorithms with automated adaptation to sample thickness and quality, image processing for focusing, and real-time feedback of focusing quality a Sophisticated Analysis Options More than 80 image processing operations, and over 300 algorithms for signal and cell feature analysis a Scalability Scanning capacities from 8 to 800 slides, optional bar code reader and immersion oil dispenser to adjust the degree of automation to the require- ments

goes back to those positions and automatically acquires images using high- resolution optics. Up to 12 color channels can be defined for acquisition. Required objectives and/or fluorescence filters are engaged automatically. The immersion oil dispenser prepares slides for the use of high-power lenses. CHROMOSOME Therefore, the system is perfectly suit- ed for high throughput or even 24/7 operating modes.

IMAGING Training and Workflow Optimization Metafer's metaphase finder comes Automation of metaphase finding and with a number of intelligent training imaging is one of the most efficient ways and optimization routines for adapting for improving throughput and quality in search algorithms to different scenar- classical cytogenetics. MetaSystems offers ios. For instance, search classifiers can a modern and flexible imaging solution be trained to assign quality scores to all for routine applications which is based on metaphases. The automated image automated metaphase finding, intelligent acquisition can then be set to automati- unattended image acquisition, and cally select a predefined number of sophisticated case and image data man- best quality metaphases. This also agement tools. applies to clonal samples: in this case, Metafer can be set to acquire a number Finding Metaphases of best metaphases from each single The Metafer-based metaphase finder clone. automatically finds metaphases on any human or non-human metaphase Data Management sample. User-trainable classifiers offer Immediately after acquisition, all an easy method to adapt the search to metaphases are available on any con- all kinds of preparations and contrast- nected NEON case and image manage- ing methods (Giemsa staining, fluores- ment station. Neon records each single cence, and even phase contrast). image, keeps track of all processing Detected metaphases are displayed in steps, and assigns images to a user. an overview gallery and can be relo- Additionally, metaphases can receive cated on the microscope stage with just customized labels for further categori- one mouse click. zation. Images can be directly opened for karyotyping or for FISH analysis. Acquisition of Images Additionally, lists of metaphase coordi- Once metaphases are detected and nates can be exported to the vernier their coordinates are stored, Metafer scales of manual microscopes.

FISH SIGNAL SCORING

MetaSystems, and its sister company cessing to enhance the results, and pattern of each nucleus simply by MetaSystems Probes (a manufacturer of acquiring all signal channels as pressing the corresponding key. high-quality DNA probes for routine use extended focus images. As a result, all Reviewed nuclei are automatically and research), work hand in hand to signals are well-focused and show the marked and the new results are dis- shape integrated analysis solutions for best definition even if the sample qual- played in a second diagram. cytogenetics, hematology and oncology. ity is poor. Automated interphase FISH analysis in sin- RapidScore is extremely efficient and gle cell samples and in tissue sections are Nuclei picked by Metafer are immedi- flexible. Cases can be shared between integral parts of Metafer's application ately displayed as a processed gallery different scorers, and Neon will auto- portfolio. MetaSystems proudly offers image. The original image of the cur- matically keep track of all results. If a RapidScore, the fastest and leanest rent nucleus and its vicinity is shown, sample has signal classes which are not workflow for precise automated and simultaneously. Scores of FISH signals part of the classifier's portfolio, it is very semi-automated FISH signal analysis. and signal fusions are displayed in the easy to create and assign a new one. RapidScore dramatically reduces the time corners of the gallery images. Metafer even proposes the class name to score and evaluate FISH cases. Additionally, Metafer assigns a class based on the automated scoring number to each nucleus, representing results. The documentation of each RapidScore the spot and fusions pattern identified. cell's analysis history in Neon mini- With RapidScore, slides labeled with mizes the requirement of making MetaSystems Probes' signals are fully One-Click Review multiple slides for the same case. and automatically scanned by the fluo- After scanning, results are available on Comprehensive customizable reports rescence imaging module of Metafer. any connected Neon station. With the can show a gallery of selected nuclei Dedicated classifiers for each FISH Metafer review module, the automati- including their signals, a diagram or a probe identify target nuclei by their cally obtained data can be reviewed table of the analysis results, and, of morphology and automatically acquire using the dedicated RapidScore course, the users who have scored the the signals. Metafer's intelligent focus- Keyboard. Each key of the keyboard case. ing and image acquisition algorithms represents one of the signal pattern analyze the sample quality while the classes defined in the Metafer classi- system is scanning, using image pro- fier. On review, users can change the y RapidScore is a unique technology to combine the reliability of automated signal detection with the flexibility of extremely fast, manual one-click reviewing.

> Thanks to Metafer, each single cell is available for review immediately after the scan. Objects can be reviewed as processed gallery images and as unprocessed original images. Users can visualize the single focus levels and the extended focus image of the latter. MAGAZINES FEEDER MODULE AUTOOILER

Metafer‘s slide frame magazines The rotating module of the If the current workflow requires hold 16 frames with 5 slides each SlideFeeder x80 delivers the slide the use of an immersion oil (80 slides in total). A fully equip- frames to the motorized stage of objective, the automated oil ped SlideFeeder x80 hosts 10 Metafer. dispensing device is engaged. magazines plus one bar code reader. The device runs unattended and Detailed sample dependent is prepared for 24/7 operation - macros control optimal oil Each magazine is portable and including intelligent priority dispersal for each sample. can easily be taken to the work- sample handling. bench for loading. CAMERAS MICROSCOPE SOFTWARE

Metafer users can choose Metafer integrates a motorized, The PC based Metafer software between four different CoolCube high-end research microscope controls the scanning hardware digital camera models. All models equipped with a stepping-motor and provides a convenient user are available as monochrome or stage of the highest precision. interface prepared for all-day, color versions. routine use. Thanks to the All features of the microscope are exceptional classifier concept The outstanding performance of directly driven by the Metafer each Metafer provides the MetaSystems‘ CoolCube cameras software. optimal balance between is optimally exploited by Metafer. flexibility and standardization. Since the first Metafer model was installed over thirty years ago , the system has been continuously optimized and now also detects objects other than metaphases and FISH signals. Today, every Metafer system is capable of detecting cells, nuclei, subcellular structures, or other items while unattended. Metafer users can choose from more than 300 parameters to specify their target objects. Like in the metaphase finder mode, each detected object is displayed in the gallery allowing for immediate review. Therefore, Metafer is utilized worldwide wherever swift, repro- ducible and reliable object recognition is required. < Based on more than 300 feature detection algorithms, Metafer reliably quantifies markers like micronuclei in rodent erythrocytes for the in-vivo micronucleus assay.

The possibility to combine different markers in a single assay allows for increasing the precision of detection. To detect circulating tumor cells, for example, immune-based markers and FISH signals are analyzed in the same multi-channel scan. Y

OBJECT RECOGNITION, QUANTIFICATION & CHARACTERIZATION

Finding Rare Events to set up a detection workflow which easily possible to design protocols combines morphology criteria with which replace the manual observation To find extremely rare cells on micro- membrane markers and FISH signals. with an automated analysis by Metafer. scope slides, such as residual tumor Consequently, Metafer became the cells in blood, this often requires the Quantifying Objects most versatile tool for the analysis of correlation of different markers and There are various assays available for microscope-based genetic toxicology features. The flexibility of Metafer the quantification of residual DNA assays and for retrospective biological allows for combining multiple criteria damage in cells which were exposed dosimetry. The outstanding speed of which together precisely define the either to chemical substances or to the system, in combination with the target cells. ionizing radiation. Though the design of unrivaled reproducibility, made these assays was done based on Metafer a standard for these fields of Based on the unique strengths of the manual scoring methods, it has been work in many countries. Metafer classifier concept, it is possible SAMPLE IMAGING & VIRTUAL SLIDES

Metafer unifies the advantages of a fully ted light image and also a number of acquires high-resolution images of equipped, motorized microscope with fluorescence channels) they can be selected regions in the tissue. FISH modern, high-quality imaging automati- visualized separately. Of course, the signals are taken from different focus on. When digitizing tissue samples, a viewer also offers various tools to levels and single focus planes and the Metafer system is therefore not restricted enhance and optimize the images. combined focus images are stored. to just some magnifications or contra- Cells are pre-segmented using sting modes. Smart Workflow Metafer's sophisticated segmentation Metafer offers a number of smart algorithms. After the acquisition, the Sample Digitization scanning and analysis workflows for user can open each image in the Metafer generates outstanding high- the pathologist. Due to the flexibility of dedicated TissueFISH software. With quality images from all samples under the system, it is easy to digitize and the mouse, or with an interactive pen, transmitted light conditions, fluores- match two consecutive tissue sections. single cells can be encircled and cence, and even from samples contras- Regions marked on a digital image marked for analysis. If the intelligent ted with phase contrast, polarized light, taken from an IHC / H&E sample are cell segmentation tool is chosen, the or dark field. Images can be composed automatically transferred to the image software automatically detects the of an unlimited number of focus planes of a neighboring section. Metafer's contour of the nuclei within the user- and can hold information about cells algorithms match the regions even if selected circle. Nuclei pre-segmented and signals, single subsections of the images are rotated, mirrored or by the software can easily be marked tissue, user annotations, alignment distorted. Once determined, the region with just a mouse click. marks, and much more. Images and can be acquired and analyzed by metadata can be visualized and Metafer, for example, with the Immediately with the selection or annotated off-site with the dedicated TissueFISH tool. marking of a nucleus, Metafer applies viewer software, or with an internet automated analysis settings to it; a gallery image is generated, and the browser. Since focus planes are stored TissueFISH analysis results are added to the data separately, it is possible to virtually The Metafer TissueFISH tool applies the histogram. If all suitable nuclei from the move through the sample along the Z advantages of RapidScore to the current image are obtained, the user is axis. If an image contains different analysis of FISH signals in tissue asked to proceed with the next camera color channels (for example a transmit- sections. For TissueFISH, Metafer field. After finishing all fields, or after collecting enough cells for the assay, the gallery can be reviewed using the innovative and swift RapidScore procedure.

TMA All tissue analysis features of Metafer can also be applied to tissue microar- y rays (TMAs). The integrated intelligent Metafer generates high-quality images TMA tool of Metafer uses special from microscope samples, for example algorithms to match the structural from Gram slides. layout of any TMA with the actual > image. Metafer then assigns the core Metafer‘s software provides several tools to designations to each single nucleus help match neighboring tissues and assign analyzed and prepares the resulting images and results to tissue microarray data for single core reporting. (TMA) cores. METAFER APPLICATIONS*

Clinical Cytogenetics, Direct Multiplex Imaging (DMI) is a Hematology, Oncology novel molecular platform technology MORE ... Metafer and the Neon case and image that precisely and reproducibly identi- data management tool were created to fies and differentiates pathogens. The Are you facing an imaging optimize routine work in small, assay is performed on microscope automation task which was not medium sized and large laboratories. slides and is evaluated on the Metafer mentioned here? It is likely that Decentralized data and workflow system. Used together with automated Metafer can help. Contact management, high-throughput slide digitization of Gram stained samples, MetaSystems today to learn more s c a n n i n g f o r m e t a p h a s e s a n d DMI results provide valuable informati- about the specific solution for interphases, karyotyping, FISH and on to facilitate a fast decision-making your imaging problem. multicolor FISH analysis stations, and a process for the selection of appropriate growing portfolio of FISH probes from antibiotics. Additionally, Metafer [email protected] MetaSystems Probes take the tedious detects and counts mycobac- parts of routine image analysis away, teria in standard blood smear thus providing the staff more preparations. time to complete the more discerning tasks. Pathology With the slide scanning platform Toxicology and Metafer, MetaSystems offers an exten- Radiation Protection sive toolbox to digitize, analyze, and Standardization of analysis is the core share larger microscopic samples such benefit of Metafer for DNA damage as tissue sections. Using sophisticated quantification. Metafer, having algorithms, Metafer generates high- removed scoring bias from toxicology quality digital copies of a slide. Images tests and biological dosimetry, opens provide focus stacks and all relevant the path to inter-laboratory compari- meta data (such as information on the sons of quantitative biological data. As location of cells). Users can create their a result, the system is part of the meth- own annotations, generate snapshots odology of many international radia- from the main image, and display tion protection networks and pre- different color channels separately on clinical tests for chemical the same screen. Dedicated software toxicology are often based on tools allow users to interpret tissue Metafer analyses. micro-array cores, or to match consecutive tissue sections. Neon integrates all workflow compo- Microbiology nents and keeps track of the Rapid identification of pathogens is process. crucial for successful treatment of infectious diseases. MetaSystems * MetaSystems products are used in many countries worldwi- Indigo, the microbiology brand of de. Depending on the regulations of the respective country or region, some products may not be used for clinical diagnostics . MetaSystems, offers several imaging In Europe, MetaSystems devices are CE certified in-vitro tools to support infectious disease diagnostics (IVD) devices. In the United States of America (USA), MetaSystems has received a 510(k) clearance for the Ikaros management and, in consequence, to karyotyping system. All other MetaSystems instruments are help reduce hospitalization costs. intended to be used for research only. Neon helps to achieve maximum control over all imaging and data handling procedures. Patients, physi- cians, and technicians benefit from consistent documentation, secure handling of sensitive data, and user- friendliness in all procedures. Neon's flexibility assures seamless integration of the system with existing procedures. Analysis steps, for example, can be NEON individually defined, and then composed to represent the complete workflow. In analysis, each stage of the Neon, a tool for flexible and consistent workflow can either be assigned to a image and case data management, is the case manually (by authorized users), or backbone of MetaSystems workstations. automatically based on predefined It was designed to collect data from conditions. different sources, and to unite them to form an efficient and well structured Image Management workflow. Neon reliably manages cases, Images acquired by Metafer can be images, and results of Metafer systems, identified based on the information on single workstations, and of large multi- their bar code labels: Neon ensures user installations. It guarantees that all that the sample information is auto- relevant information is visible whenever matically merged with the respective and wherever it is needed. Neon‘s power- case. ful and flexible workflow settings facilitate seamless integration with existing rou- Results Documentation tines and allow for the use of a variety of Neon also offers two strong tools to different imaging applications. summarize and report all data: the powerful case statistics package and Data and the reporting engine with graphic Workflow Management template editor. The statistics package Neon organizes and displays informa- can be used to query all data and to tion in an extremely efficient and summarize the results graphically and customizable way. Neon users always as tables. Results of queries can also be have access to exact information on implemented in report templates. case status, history of images, analysis Reports can be printed, saved as a PDF results, and much more. Data import files, or exported to external software; and export, even with customized data this allows for the results of the analy- fields and global, cross-application ses to be provided to clients, or shared reports, facilitate daily work. with colleagues around the world. Innovative Solutions for y MetaSystems MetaSystems Automated Imaging Document No. BRO-Metafer-2017-10-06-P © 2017 b

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