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MIAS-2 microscopy readers

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Download MIAS-2 & eaZYX brochure (pdf, 633KB)

 

MIAS-2 readers are a new generation of HTS microscopy readers with an unequaled blend of sensitivity, flexibility and speed.  They are designed to cover the throughput and flexibility needs at multiple phases across the R&D value chain.  In drug discovery R&D, applications include target identification, target validation, assay development, high throughput screening, hit-to-lead, deep pharmacology and ADMET. 

 

Unique features of the MIAS-2 readers at a glance:

·         multimode reading of 8 fluorescence channels plus 5 brightfield microscopy modes

·         1.25x – 63x objectives selected for high resolution (high numerical aperture)

·         ultra-precise object positioning and repositioning: below the microscope resolution of 0.35 micrometer

·         versaTILE technology: unlimited capturing of large areas at high resolution 

·         versaTIME technology: powerful time-lapse and video analysis for assay optimization and kinetic analysis

·         object-based auto-robust focusing in regular and low light conditions

·         intensified camera for extreme sensitivity and reduced phototoxicity

·         hands-on operation’ to 90, 210 or 300-plate screening capacity

 

Multimode microscopy reading in a most flexible way

MIAS-2 readers offer an advanced level of motorization of the light paths and full integration with eaZYX software. 

MIAS-2 reader family features up to a total of 13 different microscopy modes: five brightfield microscopy modes (MIAS-2 TRUVIEW) plus four (MIAS-2 SENSVIEW) or eight (MIAS-2 FLEXVIEW) fluorescent channels covering blue to deep red reading.  The MIAS-2 SENSVIEW reader with four fluorescent modes has been optimized for sensitivity, the MIAS-2 FLEXVIEW reader with eight fluorescent modes for flexibility (across the visible spectrum).  The brightfield and fluorescent modes of MIAS-2 readers will be customized to fit to your assay repertoire needs. 
Multimode microscopy reading is fully supported for a range of six high-quality objectives, selected for their excellent resolution (high numerical aperture) and performing fluorescence characteristics.  With the 40x objective, in-plane resolution is 0.35 micron (XY) and a focal depth (Z) of 0.89 micrometer.  For ultimate flexibility, three intermediary magnifications allow to adjust the size of objects to the pixel size on the camera CCD chips that is optimal for image analysis. 

 

Ultra-precise object positioning and repositioning

The object positioning hardware of the MIAS-2 readers in the XY dimensions and in Z, the focal plane, has a precision that exceeds the resolution of the reader.  Ultra-precise object positioning speeds up the process of multimode reading.  In the course of the first reading cycle, the XY and focal (Z) positions that were visited and imaged are stored by the eaZYX software.  The XYZ coordinates are used to revisit exactly the same XYZ positions in plates during all subsequent microscopy modes, without the need to focus again.   As a result, the images captures in different microscopy modes will be sharp and perfectly aligned, leading to perfect image analysis results across microscopy modes. 
Ultra-precise object positioning creates multiple new options to capture images in most versatile ways with the MIAS-2 and eaZYX software. 

·         The versaTILE technology facilitates capturing of large areas at high resolution. 
Regardless of the magnification used, versaTILE technology will shift the object precisely to create composing images that automatically match at their borders.   Objects on the borders are precisely reconstituted in the image tile to allow unbiased image analysis of all objects in one image tile.  The composing images are ‘pixel matched’ by ultra-precise the MIAS-2 object positioning hardware.  In this way, multimode reading of assays can be easily adapted to the assay conditions.  The users freely combine a selection of magnification and size of the image tile, according to statistical and image quality requirements of the assay.  The versaTILE technology also features automated object edge detection of wells or e.g. tissue sections. 

·         The versaTIME technology for time-lapse video-based analysis and kinetics. 
Pixel-matched revisiting of positions also allows producing multiple time-lapse video’s in parallel in the MIAS-2 reader.  The only limiting factor to the number is the time you allow between cycles.  The advanced time-lapse feature allows full automation of assay time point optimization.  versaTIME technology supports time-lapse analysis combined with multimode reading and real-time video. 

 

Intensified camera for extreme sensitivity and reduced phototoxicity

MIAS-2 readers are equipped with state-of-the-art B/W or color cameras plus an ultra-sensitive intensified camera.  The color and black and white (B/W) camera combination supports recording of fluorescent signals of high to moderate and low intensity, typically created by today’s assay technology.  They also capture high-quality color and B/W images for documentation and images analysis purposes.  The MIAS-2 intensified camera features ‘weak signal reading’ for increased sensitivity and lower phototoxicity. 

In combination with the robust, object-based auto-focus technology of eaZYX software, the MIAS-2 readers will flawlessly focus on signals ‘invisible’ to the human eye through the microscope eyepieces and bring them to life on the computer screen.  In this way, MIAS-2 becomes the instrument to access biology and assays development for low abundance targets or for targets expressed at more physiological expression levels under the control of weaker gene promoter(s).  Also, ‘low light reading’ with MIAS-2 will lead to the elimination of signal amplification steps and to the use of lower assay reagent concentrations.  Significant savings on assay cost and reductions in assay time will result from the use of the MIAS-2 reader. 
The ability to observe with ‘low light input’ is another advantage of the intensified camera.  The MIAS-2 readers can read fluorescent signals of moderate or high intensity adequately with strongly reduced excitation light input.  This feature reduces or even eliminates phototoxicity to living cells and small animal models organisms.  Likewise, ‘low light input reading’ significantly increases the lifetime of fluorescent probes.  In particular in long-term, multimode time lapse observation, ‘low light input reading’ is a very useful feature.  To exploit the advantage of ‘low light input reading’ maximally, MIAS-2 readers are equipped with a motorized filter wheel to reduce excitation light over a range of three decades. 

‘Low light reading’ and ’low light-input reading’ apply to hands on observation and to high throughput screening (HTS) alike. 

 

Wide range of object carriers & assay applications

HTS applications include cell-based assays, tissue-based assays, (behavioral) small model organism screens (zebra fish, C. elegans, Drosophila, Arabidopsis), ADMET assays, in vitro and in vivo, with living and fixed objects. 

MIAS-2 readers accept multi-well plates, Petri Dishes, micro-arrays and microscope slides placed in specific carriers fitting the 96-multiwell plate footprint.  Likewise, MIAS-2 also reads tissues and tissue sections for histology and histopathology, blood smears, microarrays, … from preclinical (transgenic) animal studies and/or clinical studies. 

 

’Hands-on operation’ to 90, 210 or 300-plate screening capacity

MIAS-2 readers conveniently allow ‘hand-on observation’ of brightfield, fluorescent as well as sub-visual signals.  Automation options of MIAS-2 readers include 90-, 210- or 300-plate stacking robotics in stand alone set up.  Embedding in a wide range of HTS robotics is supported using robust client server software. 

 

MIAS-2 is ideally suited as a pivotal platform with application across the R&D value chain. 

 

Additions and extensions on MIAS-2 are currently in development. 

 

eaZYX software for biological imaging

PRODUCTS  | TOP  |  MIAS-2 readers |  eaZYX software

 

Downloads:

The MIAS-2 & eaZYX technical brochure (pdf, 633KB)

 

eaZYX is a high-end and yet easy-to-use software platform for image acquisition, analysis that is composed of three parts: eaZYX-IMAGING, eaZYX-PROOFING and eaZYX-AUTOMATION. 

 

eaZYX-IMAGING is the image analysis core software engine

Unlike many image analysis softwares, eaZYX uses a holistic principle to ‘look’ at images.  It does not segment pixel information to pull forward certain features in the image using a ‘pixel-by-pixel’ image segmentation.  It applies the principles of ‘Scale Space’ theory to microscopic images (Van Osta et al., 2002).  eaZYX uses the entire image content: the pixel features as well as their spatial context to identify objects (groups of pixels) based on shape, spectral and intensity characteristics. 

These powerful tools were applied to create the patented object-based auto-focusing tools of the MIAS-2 readers (Geusebroek, 2000) that allow robust real-time auto focusing in extreme low light conditions.  They also form the basis from which numerous eaZYX-IMAGING applications have been developed. 

 

eaZYX-software supports high-end image analysis in two ways

eaZYX-IMAGING is your work environment to develop and store your own image segmentation scripts and applications.  Within eaZYX-IMAGING, you will select (batches of) images from disk or server; you will select the image analysis application and initiate the analysis of the image (batch).  eaZYX-IMAGING will produce detailed result data tables with descriptive statistics summaries for the identified objects.  The result data files (and derived images) are ‘database ready’ for further analysis in spreadsheet programs, in bio-statistical software, in bio-informatics-, in drug discovery- or image databases for further evaluation. 

eaZYX-PROOFING is a set of easy-to-use, on-image proofing tools for the researcher to review or approve large sets of assay results quickly.  These proofing tools conveniently relate the output data tables directly to objects in images and vice-versa. 

 

eaZYX-IMAGING & PROOFING is an open work environment

eaZYX imaging exports and imports standard B/W (jpeg, TIFF), color (TIFF) image and video (Quicktime) file types.  You can import image files or batches of image files in standard file formats from other readers for analysis within eaZYX-IMAGING & PROOFING.   Likewise, e.g. in combination with the MIAS-2, eaZYX will export images or batches of images or video in standard file formats for analysis in the image analysis software package preferred or by you or your team of image analysis experts. 

 

When installed on an iBOX as a stand alone set up, eaZYX-IMAGING will control all processes from ‘image batch to database-ready result’.

 

In combination with a MIAS-2 microscopy reader, eaZYX-IMAGING provides proprietary ‘embedded applications’ for robust object-based auto focusing, which allows the eaZYX-AUTOMATION software and MIAS-2 to capture sharp images automatically, even in extreme low light conditions. 

 

eaZYX-AUTOMATION reader software

eaZYX-AUTOMATION reader software handles all functions ‘upstream’ of the image storage and/or analysis process.  In eaZYX-AUTOMATION you can build, store, copy and edit your own image capture protocols, through an intuitive single setup window.  While you are editing your protocols, live viewing will immediately show the result of each of your actions.  These features are an essential support when viewing signals from low light applications where the signal is too low to be visible to the eye.

 

eaZYX-AUTOMATION sets and schedules all the components of the MIAS-2 reader, such as e.g. the different selected microscopy modes and the sequence of capture; the way in which images are captured; individually, tiled images, video and/or time-lapse movies per object, per well, per plate or per batch of plates.  It comprises the advanced applications of versaTILE and versaTIME technology.  It runs embedded eaZYX-IMAGING applications, such as the proprietary routines for robust object based auto-focusing in low light.  Captured images, image tiles and video are stored in their relational multi-mode and meta context for image analysis in e.g. eaZYX-IMAGING. 

 

eaZYX-AUTOMATION plate handling software

In installations of MIAS-2 which include plate handling robotics or embedding into HTS backbones, the eaZYX-AUTOMATION plate handling software is delivered.  It handles plate stacking robotics and supports communication with the scheduling software of HTS backbones.  eaZYX-AUTOMATION plate handling software is of a modular architecture that facilitates fast integration of MIAS-2 into scheduling software of robotic HTS backbones. 

 

eaZYX-iBOXes, tailored computer hardware to run eaZYX software and MIAS-2 readers

As a stand alone set up, the eaZYX-iBOX is the hardware platform on which you can run image analysis using the eaZYX-IMAGING software.  In combination with a MIAS-2 reader and/or robotics, your eaZYX-iBOX will be the centre from which you observe with MIAS-2 or execute screening campaigns with ‘plate stack to database-ready result’ level automation.  You will run the MIAS-2 reader, the robotics and image analysis from your iBOX. 

Depending on the nature of your platform (stand alone or with reader/robotics), your research activities, the level of automation needed, your local server and network facilities and the need to perform image analysis while capturing images with MIAS-2, your needs for computing power and image storage capacity may differ. 

Three eaZYX-iBOX solutions have been developed. 

·         We propose the eaZYX-iBOX Workstation when your work environment has a broadband network (100Mb) and large server storage volume available, and when you use a MIAS-2 without plate robotics for experiments that create moderate data volumes (typically <30Gb). 

·         The eaZYX-iBOX Power Workstation provides more computing power to accommodate parallel image acquisition and image analysis.  Network and server requirements are identical to those of the eaZYX-iBOX Workstation. 

·         In case no broadband network and/or server storage volume or high-end users of MIAS-2 with plate handling robotics, the eaZYX-iBOX Volume Workstation is the better solution.  It provides 420 Gb internal disk storage volume, stepwise upgradeable with another 1 Terabyte, by addition of up to 7 external disks.  A tape backup module is included in the eaZYX-iBOX Volume Workstation and optional for the other two iBOXes.