MetaXpress High-Content Image Acquisition and Analysis Software

Flexible and intuitive high-content analysis transforms images to results

The MetaXpress® Software works with ImageXpress® Systems to acquire high-resolution images, recognize and segment objects, extract features, and convert this information into meaningful data. The software satisfies multiple levels of analysis flexibility and complexity, and is further accelerated with MetaXpress® PowerCore High-Content Distributed Image Analysis Software for increased throughput. High-content analysis data is seamlessly managed by the MDCStore™ Data Management Solution, and transferred to the AcuityXpress™ High-Content Informatics Software for data QC, visualization and mining.

Multi-level analysis tools covering a wide range of imaging applications are all available in one software package.

  • Application Modules: turnkey solutions for most common analysis routines
  • Custom Modules: flexible toolbox for building specialized analysis
  • Journals: powerful macros for analyzing complex and unique applications

Plate acquisition setup wizard quickly steps users through the image acquisition process and its optimization.

  • Objective and sample selector lets you choose from a wide variety of supported objectives (1-100x) and samples (SBS footprint microplates or microscope slides).
  • Interactive display of field-of-view to easily configure acquisition sites and capture rare events using optimal settings.
  • Laser auto-focus provides the fastest focusing available to compensate for focus drift produced by temperature fluctuations, plate irregularities, and biological variability.
  • Adaptive acquisition algorithm decreases sample read times on difficult, heterogeneous samples by acquiring a desired number of cells before moving on to the next well.

Adaptive Background Correction is utilized in all MetaXpress Software Application Modules to compensate for uneven background intensity to improve image segmentation.

Adaptive Background Correction mitigates poor sample quality while improving image segmentation.
(Left) Unevenly stained sample before segmentation (Center) after conventional segmentation,
some of the features are not identified (Right) with Adaptive Background Correction, all the
features are identified.
Field-by-Field Data, Cell-by-Cell Data, and Segmentation Overlays are made available to ensure in-depth downstream analysis such as identifying different cell populations or reviewing accuracy of segmentation
Field-by-Field Data, Cell-by-Cell Data, and Segmentation Overlays are made available to ensure in-depth downstream analysis
All data parameters can be reported as a summary of the field of view or for each individual cell. 
 

18 MetaXpress Application Modules provide turnkey solutions for most common analysis routines. Through an interactive interface, these pre-designed application modules can be easily set up in minutes.

Micronuclei Application Module

Micronuclei Application Module classifies cells based on nuclear morphology for genotoxicity applications but is also ideal for cell health or multi-nucleated cell populations with additional markers for analysis of apoptosis, necrosis or to distinguish any small structure next to a large one such as a yeast bud.

  • Highly accurate classification of cells (micro-, mono-, bi-, or multi-nucleate) achieved with proprietary algorithm to discriminate phenotypes based on cell morphology, number of nuclei, distance of micronuclei from nucleus, micronuclei vs. "blebs" or "buds".
  • Only requires a single fluorophore (nuclear stain) to identify cells in various classifications, eliminating the requirement for a cytoplasm stain, thereby reducing sample preparation, image acquisition and analysis time.
  • Use of two additional fluorophores facilitates further phenotypic analysis, such as transfection markers to identify transfected cells or kinetochore markers to differentiate micronuclei originating from clastogens (which create acentric chromosomal fragments) or from aneugens (which cause whole chromosomal losses).
metaxpress_appmod_micronuclei_450.jpg
Images of cell nuclei before (left) and after (right) image segmentation.
Micronuclei, binucleate, and mutinucleate cells detected by the application
module are highlighted. In total, more than 60 measurements per image
and 30 measurements per cell are available to assist with identification
of the wide range of phenotypes associated with genotoxicity studies.

Neurite outgrowth Application Module

Neurite Outgrowth Application Module is designed to measure and characterize outgrowths, the extension of processes from the cell body, which are natural parts of neuronal development. Inhibition or stimulation of neurite outgrowth is implicated in a broad range of neurological disorders or injuries including stroke, Parkinson's disease, Alzheimer's disease, and spinal cord injuries.

  • Unique assay that cannot be performed without imaging
  • Provides consistent results faster than manual tracing and counting
  • Output parameters, on a per field-of-view or per cell basis may include outgrowth count, mean or maximum lengths, branches, straightness, cell number or cell body size, or % with significant growth
metaxpress_appmod_neurite_450.jpg
(Left) Images of fluorescently stained neurons. (Right) After image segmentation.
Each outgrowth is assigned to a cell body. All the outgrowths and cell bodies are
then measured. (Courtesy of Kris Poulsen and Davide Foletti, Rinat Neuroscience
Corporation).

Angiogenesis Tube Formation Application Module

Angiogenesis Tube Formation Application Module facilitates the analysis of tube formation, a model experimental system for angiogenesis. The promotion or inhibition of blood vessel formation is one focus for cancer, diabetes and other vascular disease research. 

  • Captures the three-dimensional behavior of tubes utilizing Z-stack acquisition available through the MetaXpress Software
  • A best-focus image of the z-stack is analyzed to characterize tubes by area, length, branch points, and nodes
metaxpress_appmod_angiogenesis_450.jpg
Human Mammary Epithelial Cells (HMEC-1) tube formation. (Left) 3D Acquisition
(Center) Best focus algorithm collapses z-series into a single image
(Right) tubes and nodes are identified with the application module (Data
courtesy of BD Biosciences)

Mitotic Index Application Module

Mitotic Index Application Module is designed for the quantitative discrimination of mitotic and interphase cells, a critical tool for oncology drug discovery programs, providing insight into potential anti-cancer therapeutics that rely on arresting mitosis in cancerous cells to prevent uncontrolled proliferation.

metaxpress_appmod_mitoticindex_450.jpg
(Left) CHO-K1 cells treated with Nocodazole for 18 hours before staining with
a marker for mitotic arrest. (Right) After image segmentation the
green mask identifies mitotic cells and red indicates nuclei in interphase.

Cell Cycle Application Module

Cell Cycle Application Module classifies and quantifies cells in various stages of the cell cycle to investigate cell cycle progression. In healthy non-cancerous cells, challenges with DNA damage, hypoxia, metabolic changes or spindle disruption result in the triggering of checkpoints and cell cycle arrest. Cancerous cells commonly lose checkpoints and divide uncontrollably, even in challenging conditions. With the appropriate tools, researchers can screen for drugs that cause cell cycle arrest or cell death in cancerous cells.

  • Differentiates 5 phases of the cell cycle using only a nuclear stain (G0/G1, S, G2, Early or Late M).
  • Optional detection of mitosis with specific fluorophores to better distinguish M-phase cells when using low magnification.
  • Optional detection of apoptotic markers to detect conditions that trigger apoptosis.
  • Interactive color-coded graphs to easily set classification cutoffs. 
metaxpress_appmod_cellcycle.gif
Classification and quantification of cells in 5 phases of the cell cycle. Interactive color
coded graphs allow to easily set classification cutoffs.

Monopole Detection Application Module

Monopole Detection Application Module monitors the disruption of the formation of bipolar spindles, a successful mechanism used by drugs such monastol to stop the progression of cancerous cells through mitosis. The module quantifies mitotic cells with monopolar or bipolar spindles in cells stained with a DNA probe and a microtubule probe.

metaxpress_appmod_monopoles_450.jpg
(Left) 3T3-L1 mouse fibroblast cells treated with monastrol and stained for beta tubulin.
Nuclei are stained with Hoechst. (Right) the module identifies interphase cells (red), bipolar
spindles (blue) and monopoles (green).

Cell Scoring Application Module

Cell Scoring Application Module is a general and flexible solution to identify subpopulations of cells tagged with a second fluorescent probe and is ideal for examining transfection efficiencies, pathway activation (kinases) or adipogenesis.

  • Label all cells with a nuclear or whole cell stain and only cells-of-interest will exhibit staining of the target with a second fluorophore
  • Robust identification of cells exhibiting markers for DNA damage, differentiation, or other selective activation
  • Equally accurate at low or high magnification
  • Output results as number or percent positive or negative or include fluorescence intensity values of each cell or as a total or average of the field-of-view.
metaxpress_appmod_cellscoring_450.jpg
(Left-top) HeLa cells labeled with DAPI. (Left-bottom) Immunostaining for target marker.
(Center-top) Cell Scoring identifies all nuclei (red). (Center-bottom) Cell Scoring
Application Module identifies immunostaining positive. (Right) Overlay shows
cells positive for marker (green) and negative for marker (red). 

Multi-Wavelength Cell Scoring Application Module

Multi-Wavelength Cell Scoring Application Module enhances the functionality of the Cell Scoring Application Module to include additional wavelengths to score populations of cells based on numerous labels.

  • Up to seven fluorescent wavelengths can be analyzed simultaneously to customize analysis for multiple markers (or analyze the same marker with different settings)
  • Stained area may be defined as nucleus, cytoplasm, or whole cell for best segmentation

metaxpress_appmod_mwcs_450.jpg

Count Nuclei And Cell Proliferation HT Application Modules

Count Nuclei and Cell Proliferation HT Application Modules automate accurate counting of nuclei for most types of cells and are ideal for the study of cell proliferation, cell counting or cell migration. These modules count nuclei even when the background is uneven, providing superior segmentation compared to simple thresholding.

  • Both modules identify nuclei, taking into consideration nuclear size and varying background intensities
    • Touching objects are automatically split
    • More consistent between users and faster than manual counting.
    • Easier and faster than flow cytometry, which is a low-throughput method that requires trypsinization of cells
  • Cell Proliferation HT Application Module is a high throughput version of the Count Nuclei Application Module, (about 1 minute for 96-well plate at one site per well without the MetaXpress® PowerCore™ Software) with a simplified detection algorithm, which provides site summary data only (not cell-by-cell) and does not save segmentation overlays to the MDCStore Database.
metaxpress_appmod_countnuclei_450.jpg
(Left) Image has uneven illumination and touching cells. (Right) the module
identifies touching cells as separate objects (as indicated by the red arrow).
Adaptive Background Correction compensates for the variable background
intensity - even when background intensity in one area of the image is greater
than nuclei intensity in another area.

Cell Health Application Module

Cell Health Application Module classifies cells states in viable, early apoptosis, late apoptosis or necrosis.

  • 3 wavelength detection of nuclear or cytoplasmic staining 
  • Scores cells as viable, necrotic, early/late apoptotic based on intensity of markers
  • Site-by-site data including counts, percentages, total and average area and intensity
  • Cell-by-cell data including health status, area and intensity measurements
  • Validated with most common cell health dyes such as Yo-Pro 1, Annexin V or CellEvent Caspase 3/7 for apoptosis, Propidium Iodide for necrosis, or mitotoxicity dyes such as JC-1 or JC-10 to study loss of mitochondrial potential
metaxpress_appmod_cellhealth_450.jpg
(Left) Cells were treated with 1 μM Staurosporine for 12 hours and stained
with Hoechst 33342, YO-PRO-1 and PI (Right) Image analysis results are shown as a
colored overlay on the source image. Viable nuclei are shown in green. Early
apoptotic nuclei are shown in blue. Late apoptotic nuclei are shown in purple.
Necrotic nuclei are shown in red.

Live/Dead Application Module

Live Dead Application Module is compatible with commercially available Live/Dead assay kits designed to study cell proliferation or death. Common applications monitor cell proliferation associated with cancer or cell death due to neuromuscular diseases such as Alzheimer's and Parkinson's Disease or in response to cytotoxic and apoptotic events.

  • 2 wavelength present in any part of the cell, not necessarily the nucleus
  • Scores cells as live or dead based on intensity of markers
  • Site-by-site data including counts, percentages, total and average area and intensity
  • Cell-by-cell data including classification, area and intensity measurements
metaxpress_appmod_livedead_450.jpg
(Left) Cells were treated with 1 µM Staurosporine. (Right) Red
objects are live cells and green objects are dead.

Granularity, Transfluor and Transfluor HT Application Modules

Granularity, Transfluor and Transfluor HT Application Modules facilitate the analysis of punctate structures such as the one observed during clustering of target molecules for receptor internalization or within the nucleus or even the punctate patterns of mitochondria or other organelles.

  • 1-2 wavelengths (stain of interest for punctate structures, optional nuclear stain)
  • Transfluor Application Module detects smaller pits and larger vesicles in the same wavelength simultaneously and is optimized for the Transfluor universal GPCR assay
  • Transfluor HT Application Module is a high throughput version of the Granularity Application Module for fast screening (about 1 minute for 96-well plate at one site per well without the MetaXpress PowerCore Software) with a simplified detection algorithm, which provides site summary data only (not cell-by-cell) and does not save segmentation overlays to the MDCStore Database.
U2OS cells (left), overlay (right). The module identifies granules and nuclei, even
in cells with high background (red arrow).
metaxpress_appmod_transfluorHT_450.jpg
(Left) Phagocytosis is detected by incorproation of a green fluorescently
labeled antibody. Cells are detected with a blue nuclear dye. (Right)
The module identifies nuclei as blue and phagocytic structures as red.

Translocation, Translocation-Enhanced, Multi-Wavelength Translocation and Nuclear Translocation HT Application Modules

Translocation, Translocation-Enhanced, Multi-Wavelength Translocation and Nuclear Translocation HT Application Modules quantify the correlation between probes and compartments with four modules available to fit your needs.

  • The Translocation Application Module is ideal for studying general cellular component movement from the cytoplasm to the nucleus with a minimum number of adjustments.
  • The Translocation-Enhanced Application Module offers increased functionality over the Translocation Application Module with finer definition of regions for translocation and the option to study translocation in non-nuclear compartments such as mitochondria.
  • The Nuclear Translocation HT Application Module is for the fast analysis of translocation in and out of the nuclear compartment (about 1 minute for 96-well plate at one site per well without MetaXpress PowerCore Software) with a simplified detection algorithm, which provides site summary data only (not cell-by-cell) and does not save segmentation overlays to the MDCStore Database.
  • The Multi-Wavelength Translocation Application Module lets you analyze the translocation of up to 6 probes simultaneously (or the same probes with various settings), in addition to the nuclear stain.
metaxpress_appmod_translocation_450.jpg
(Left) No translocation of red probe from cytoplasm to nucleus is seen.
(Center) Translocation is visible in the center cell. (Right) Green
indicates the cell that is positive for translocation.
metaxpress_appmod_translocationHT_450.jpg
Nuclear Translocation Assay. (Left) Transcription Factor detected with a green probe.
(Center) Nuclei detected with a blue stain. (Right) The Nuclear Translocation HT
application module detects the correlation between the 2 wavelengths and the
color of the overlay indicates whether the correlation is above (red) or below (green)
a user-defined correlation threshold.

Flexible Custom Modules can be rapidly written for advanced analyses, such as identifying objects within objects, creating morphometric classifiers for shape analysis, and analyzing both color and transmitted light images. The Custom Module Editor in MetaXpress Software version 5 and above is a flexible, interactive environment where users can create and test a template for image analysis.

MetaXpress custom module can find objects localized within specific cell compartments, such as puncta in neurite outgrowths
Custom modules in MetaXpress Software can find objects localized within specific
cell compartments, such as puncta in neurite outgrowths. Segmentation
overlay shows: yellow - neurites; dark blue dots - synaptic peptides; pink - nuclei.
Non-neuronal nuclei are excluded from the analysis. 
Powerful Journal Macros can be created for unattended execution of complex multi-step routines including any hardware control and image analysis.

Designed to screen 1 million samples in as little as 2 weeks, the MetaXpress PowerCore Software harnesses the power of parallel processing to accelerate image analysis while preserving the quality of image segmentation and the numerous outputs desired for multi-parametric analysis.

Parallel processing eliminates image analysis bottlenecks.

  • Server-client platform with a server that divides plate analysis into small processes and distributes them to multiple clients. Each client, running onmulti-processor computers, executes the analysis and relays the results to the server.
  • Scalable design allows the addition of processors if higher analysis throughput is needed.
  • Integrated to the high content screening workflow ─ At the end of analysis, the server efficiently saves all data into the MDCStore™ Data Manager, allowing access to results within a laboratory or across an organization.
MetaXpress PowerCore Software accelerates the HCS workflow by significantly reducing time required for image analysis. Leveraging the power of parallel processing, MetaXpress PowerCore Software is a server-client solution that enables users to leverage a scalable number of client based processors to run the MetaXpress Software Application Module algorithms in parallel, accelerating analysis 5- to 40-fold.
MetaXpress PowerCore Software accelerates the HCS workflow by significantly
reducing time required for image analysis. With the power of parallel processing,
MetaXpress PowerCore Software is a server-client solution that enables users to leverage
a scalable number of client based processors to run the MetaXpress Software
Application Module algorithms in parallel, accelerating analysis 5- to 40-fold.
Basic configurations allow research and small screening labs to analyze plates as fast as image acquisition. Scalable licensing allow analysis speed to be tailored to the needs of your laboratory (number of instruments supported, volume of data generated, and complexity of your multi-parametric data files).

Advanced configurations are ideal for core facilities or high-throughput imaging environments and will accelerate application module speed up to 25 times faster than acquisition. With this speed, multiple ImageXpress Systems can run in parallel at full capacity, or you can re-analyze archived images in minutes.

Image analysis time per 384-well plate using the MetaXpress PowerCore Software.
Results were obtained with computers meeting recommended specifications
and IT requirements 

The MDCStore Data Management Solution organizes images and experimental information generated by multiple imaging instruments, as well as data resulting from image analysis, data analysis or visualization software, enabling seamless manipulation of complex sets of images and metadata.

  • Scalable design ensures the proper amount of image and metadata storage is available to support growing laboratory requirements, multiple users, or data retrieval during image acquisition.
  • MDCStore database schema is available for both Microsoft SQL Server or as an Oracle compliant tool that can be fully deployed by your database administration team.
  • Multiple storage options can be tailored to individual needs for environments with multiple users such as core laboratories.

See recommended computer and server specifications, and partnering IT solutions and services for high content screening. 

MDCStoreTools is a stand-alone utility to help database administrators or IT departments manage the MDCStore Data Management Solution.

  • Enables configuration of users, groups, and image storage locations in multi-user environments such as core laboratories.
  • Security policies for either Microsoft SQL Server or Oracle can be set to ensure restricted access to groups and users.
  • Optimize/grow/shrink database to ensure peak data security and performance that can be refined over time to meet your changing HCS storage needs.
  • Image and data management for archiving, back-up/restoration (SQL Server only) of old data, for attaching/detaching databases (SQL Server only), migrating data across labeled image storage locations, or selectively deleting data (all images or only image segmentation).

MDCStore software development kit (SDK) provides tools to access and exchange data with 3rd party solutions.

  • Application programming interface (API) to exchange image locations, data, and metadata with 3rd party software to facilitate communication with laboratory information management systems (LIMS), to provide alternative data analysis and visualization methods, or to analyze 3rd party images within the MDCStore Data Management Solution.
  • Easy licensing to allow users to develop their own internal, non-commercial applications to integrate with corporate databases and third party applications. Distribution and commercial licenses are also available.

For product configurations and pricing on MetaXpress Software, please please request a quote or contact us