GE Healthcare

IN Cell Analyzer 1000 Cellular Imaging and Analysis System

Now updated with:

Optical Z-sectioningEnvironmental controlRemote services diagnosticsDirect Spotfire link

Exceptional flexibility while maximizing image and data qualityIN Cell Analyzer 1000 is a modular, cellular and subcellular imaging system for fast, automated imaging and analysis in fixed and live cells. This powerful, easy-to-use instrument enhances the productivity of cell-based research by combining system flexibility with excellent image and data quality.

IN Cell Analyzer 1000 Imaging and Analysis System gives you:

• A variety of hardware and software options in a modular format for the flexibility to perform a broad range of cellular applications

• Preconfigured, easy-to-use analysis modules to maximize speed from data to results

• Developer Toolbox to write your own analysis routines for unique or unusual assays

• Excellent image quality

• Interactive data visualization to drive decisions and discovery

• The highest levels of application and service support

More results, faster for a wide range of cell imaging applicationsSpeed your research and understanding with automated, multiplexed assay imaging and analysis. High quality imaging, intuitive image analysis software, and market leading data visualization tools enable you to interpret and analyze many cellular and subcellular assay types including:

• Apoptosis• Receptor activation• Signaling pathway analysis• Calcium imaging• Toxicity• Micronuclei formation• Cell cycle reporting• Morphology analysis• Organelle and protein trafficking studies• Neuronal function• Neurite outgrowth• RNAi analysis• Cell health• Cell migration• Cell differentiation• Tissue imaging

Fig 1. Primary porcine trabecular meshwork cells stained for DNA

(blue), actin (rhodamine phalloidin, red) and paxillin in focal

adhesions (green). IN Cell Analyzer 1000 20× objective (image

courtesy of C. Laethem, Aerie Pharmaceuticals. Popular vote

winner of the IN Cell Analyzer Image Competition at the CHI High-

Content Analysis meeting, 2007).

Fig 2. NIH-3T3 fibroblasts over expressing src causing localization

of actin towards podosomes. Cells stained for DNA (blue), actin

(green), and phospho-src (red). IN Cell Analyzer 1000 (Image

courtesy of E. Griffin, Scripps Florida. Judged winner of the IN Cell

Analyzer Image Competition by a panel of experts at the CHI High-

Content Analysis meeting, 2007).

Rapid image acquisition with exceptional image resolution A fast infrared laser autofocus system ensures that all scanned cells are in focus within a sample. Acquisition speeds of up to 2000 images per hour can be achieved, reproducibly generating optimal images for high-content cellular analysis.

Standard footprint microplates can be imaged, from 6 to 384 wells. Up to four standard microscope slides with coverslips can be imaged using an optional sample holder.

A xenon lamp provides a flat field illumination from UV to infrared wavelengths. A choice of excitation and emission filters, filter cube/dichroic-based wavelength selection, and automated wavelength switching allows imaging across a broad range of biologically relevant wavelengths.

Our updated instrument has a wider choice of filters to further improve the flexibility of dye choice.

NEW – Optical Z-sectioning Module

Applications enabled by the new Optical Z-sectioning Module include:

• Enhanced image quality where high background is a problem (e.g., fluorescent compounds in medium) • Optical Z-sectioning of thick samples (e.g., tissue sections, cell clumps) • 3-D reconstruction to co-localize objects in Z-section

Fig 3. Maximum intensity projection (green = FITC, yellow = Cy™3,

red = DRAQ™5), and overlaid images (10×) of a Zebra fish fry.

A. Widefield. B. Optical Z-section.

Fig 4. Bovine pulmonary artery endothelial cells stained with mouse

monoclonal anti-tubulin antibody to label microtubules (FITC).

Modular design maximizes your investmentThe basic system may be upgraded at any time to enable kinetic assays, environmental control, optical Z-sectioning, transmitted light imaging, and microscope slide handling. Upgrades are performed in your laboratory, quickly and easily by GE Healthcare service engineers, with minimal downtime and disruption to your workflow.

This allows you to buy only the modules you need for the assays you run now, secure in the knowledge that your instrument can evolve to match your changing assay needs.

Environmental Control Module

A sample chamber maintains CO2 concentration and humidity. Environmental control prolongs cell health and viability, ensuring more reliable results from live-cell imaging assays performed over extended periods.

Temperature Control Module

The stage provides optimal, consistent microplate conditions (25 to 42°C with minimal evaporation) within the instrument. The menu-driven protocol manager allows for temperature setting and control. Continuous temperature readings during image acquisition ensure cell integrity.

Optical Z-sectioning Module

The Optical Z-sectioning Module facilitates conversion of the illumination system of a conventional wide-field microscope to a structured light imaging system. This module is a combination of hardware and proprietary software that removes out-of-focus light above and below the focal plane, thereby producing high quality images of thick samples at various depths.

Microscope Slide Imaging Module

Up to four microscope slides with coverslips may be positioned for imaging at a time. You may then define and control the specific field of view to obtain optimal results.

Transmitted Light Module

This module allows acquisition of brightfield images alone for specific morphological assays, or multiplexing of brightfield images with fluorescent images. Differential interference contrast (DIC) and phase contrast images can also be acquired.

Liquid Handling Module*

A positional gantry, equipped with a single syringe and needle, transfers liquid from a source to its destination. Two dispensing modes permit dispensing of 10 to 100 µl of reagent. The system supports aspiration and dispensing from 96-and 384-well plates and is easily cleaned using a wash station linked to a bottle of appropriate cleaning solution

* Needs to be factory fitted.

Expand your capacity

The open architecture of the IN Cell Analyzer 1000 enables you to interface with commercially available laboratory automation, analysis software, and informatics solutions for data integration, storage, and analysis.

Automation friendly

IN Cell Analyzer 1000 can be integrated with major commercially available laboratory robotics systems to support further automation of routine tasks.

Informatics enabled

IN Cell Analyzer images and result data can be integrated with proven data management, analysis, visualization, and mining tools.

New - Our Investigator Software suite includes the market leading Spotfire™ DecisionSite™, enabling interactive visual data analysis at the click of a button.

Fig 5. Automation-ready IN Cell Analyzer 1000 integrates to a

wide range of plate handling solutions such as the Twister™ II

Microplate Handler.

Turn images in to results rapidly and easilyIN Cell Analyzer 1000 is complemented by highly flexible, intuitive, and enabling image analysis software. The breadth of tools available with IN Cell Investigator software means you can analyze not only those assays in routine use today, but also other applications you may wish to investigate in the future.

IN Cell Investigator

IN Cell Investigator software offers a flexible and comprehensive solution for automated high-content image and data analysis.

The software consists of three major components:

1. IN Cell Investigator Analysis Modules provide a comprehensive range of ready to go, fully validated analysis routines to maximize speed from data to results

2. IN Cell Investigator Developer Toolbox enables you to construct your own image analysis protocols for specialized applications. The award winning Developer Toolbox now incorporates easy to use Context Modules— protocols for specific applications that can be used as a starting point for customized analysis

3. Spotfire DecisionSite Basic allows interactive visual data analysis of results from Developer Toolbox or the ready to go analysis modules

Together these components allow you to:

• Rely on validated ready to go analysis protocols enabling more than 50 applications

• Classify cells using interactive advanced hierarchical classification tools to assign cells to user-defined subpopulations

• Develop protocols for unique assays without specialist scripting knowledge

• Make decisions from complex multiparametric data by interactive visual analysis using the intuitive Spotfire DecisionSite software

In addition, IN Cell Investigator can work with files from other imagers and microscopes when using the optional IN Cell Translator Software.

Fig 6. Interactive visualization and classification of cell subpopulations

in IN Cell Investigator for a calcein-AM/propidium-iodide (PI) cell

viability assay. Live (green), dead (red), and unclassified (blue) cells were

classified by user-defined linear discriminants (blue and red lines) after

plotting the integrated nuclear intensity of calcein (green channel;

x-axis) and PI (red channel; y-axis) for individual objects.

The technology to serve you better

Bio InSite: Remote support, diagnostics, and service at your fingertips

Bio InSite™ is a highly secure digital link providing the option to connect your organization, by remote access, to a variety of services offered by GE Healthcare.

• Enhanced support: Access to Engineering and Scientific Support resources who can see what is displayed on your system remotely allowing interactive sessions or encrypted data transfer

Fig 7. Dual-area object analysis using the IN Cell

Analyzer 1000 analysis software. A composite

image showing: A. Cells expressing EGFP-2×FYVE

and stained with Hoechst™ and Mitotracker Red.

B. A close up of cells within the image shown at

top left. C. Color legend for bitmap shown in

image D. D. A bitmap overlay superimposed on

image B showing EGFP-2×FYVE endosomes

(yellow outlines, inclusion 1), mitochondria

(magenta outlines, inclusion 2), nuclei (blue

outlines), and cell bodies (green outlines).

A B

C D

• Faster response: Service engineers can troubleshoot software and hardware issues using remote diagnostic tools. If an on-site visit is still necessary, service engineers arrive well- prepared to solve the problem faster

• Increased productivity: You will be up and running again faster because significantly less time and effort is spent on describing problems and exchanging data files

• You are in control: Access can only be initiated by you

Technical specifications

IN Cell Analyzer 1000 end-point Instrument

General system specifications

Camera Pixel size 6.45 x 6.45 µm

Field of view at 10× 0.603 mm2

Cooling -30°C

Pixel layout 1392 × 1040

Focus Method Confocal laser sensor

Focus time < 400 ms

Objective positioner resolution (Piezo objective positiner) 0.2 µm

Illumination Epifluorescent lamp 100 W, xenon

Transmitted light LED

Magnifications 4×/0.20 Plan Apo

10×/0.45 Plan Apo

20×/0.45 ELWD Plan Fluor

40×/0.60 ELWD Plan Fluor

Plate positioning (XY stage) Resolution +/- 5 µm

Speed (well-to-well speed on a 96-well microplate) < 800 ms

Filter selection Excitation filters 6

Emission filters 6

Plate compatibility SBS standard footprint microplates including: 6, 12, 24, 48, 96, 384-well plates

Computer Standard Windows™ XP Professional (SP2) PC

Miscellaneous specifications

Electrical Voltage 110/240 VAC

Frequency 50 to 60 Hz

Instrument physical specifications Depth 970 mm

Width 670 mm

Height 710 mm

Weight ~ 70 kg

Service cabinet Depth 610 mm

Width 560 mm

Height 660 mm

Weight ~ 50 kg

Automation Robotics-ready and compatible with all major commercially available laboratory robotic systems

For more detailed specifications, visit www.gelifesciences.com/incellanalyzer.

Instruments and modules

IN Cell Analyzer 1000 end-point instrument 28-4051-28

Environmental Control Module 28-4084-05

Optical Z-sectioning Module 28-4051-30

Temperature Control Module 28-4063-95

Liquid Handling Module 28-4066-59

Microscope Slide Imaging Module 25-8098-19

Transmitted Light Module 28-4077-07

IN Cell Analyzer 1000 kinetic instrument* 28-4051-29

IN Cell Investigator Software

IN Cell Investigator, Single Seat License 28-4089-71

IN Cell Investigator, 5 seat License 28-4089-72

IN Cell Translator Software 28-4047-40

* Supplied with Temperature Control and Liquid Handling Modules.

Ordering Information

Fig 8. Lung carcinoma tissues stained for b-catenin using a FITC

labeled secondary antibody (green) in order to determine the

distribution of b-catenin within the cells. The nuclei are stained with

Hoechst™ 33342 (blue). IN Cell Analyzer 1000 image courtesy of K.

Gately, Trinity College Dublin.

Fig 9. Mouse N1E-115 neuroblastoma cells were cultured on rat

hippocampal astrocytes and stimulated by serum deprivation to

model neurite outgrowth in a co-culture system. Cells stained for DNA

(blue), neuronal-specific bIII-tubulin (green), and glial cell (astrocyte)-

specific GFAP (red). IN Cell Analyzer 1000 20× objective, image

courtesy of J. Cuy, Millipore.

Fig 10. Lung cancer cells stained for b-catenin using a FITC labeled

secondary antibody (green) and the nuclei are stained with Hoecsht

(red). IN Cell Analyzer 1000 image courtesy of K. Gately, Trinity

College Dublin.

For local office contact information, visit www.gelifesciences.com/contact

GE Healthcare Bio-Sciences Corp800 Centennial AvenueP.O. Box 1327Piscataway, NJ 08855-1327USA

www.gelifesciences.com/incellanalyzer

GE, imagination at work, and GE monogram are trademarks of General Electric Company.

InSite and Cy are trademarks of GE Healthcare companies.

The IN Cell Analyzer 1000 is the subject of US patent application number 10/514925, together with other pending family members, in the name of GE Healthcare Niagara, Inc.

The IN Cell Analyzer 1000 and associated analysis modules are sold under license from Cellomics Inc. under US patent numbers US 6573039, 5989835, 6671624, 6416959, 6727071, 6716588, 6620591, 6759206; Canadian patent numbers CA 2328194, 2362117, 2282658; Australian patent number AU 730100; European patent number EP 1155304; Japanese patent number JP 3466568 and equivalent patents and patent applications in other countries.

All third party trademarks are the property of their respective owners.

© 2006—2007 General Electric Company—All rights reserved.

First published May 2006

All goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them. A copy of these terms and conditions is available on request. Contact your local GE Healthcare representative for the most current information.

GE Healthcare Bio-Sciences AB Björkgatan 30 751 84 Uppsala Sweden

GE Healthcare UK Ltd Amersham Place Little Chalfont Buckinghamshire HP7 9NA UK

GE Healthcare Europe GmbH Munzinger Strasse 5, D-79111 Freiburg Germany

GE Healthcare Bio-Sciences KK Sanken Bldg. 3-25-1, Hyakunincho Shinjuku-ku, Tokyo 169-0073 Japan

06/2007 28-9184-29 AA