Cell Based Screening System With Automated Imaging Assays The Discovery-1™ System will screen 96, 384, and 1536-well plates, up to 8 probes per well and up to 16 sites per well. Integrated System for High Content Screening Applications www.discovery-1.com The headquarters of Universal Imaging Corporation in Downingtown, PA, is home to Universal Imaging Institute, the site of our in-house training courses. Discovery-1 Screening System Evolves from History of Live Cell Imaging Microscopy and fluorescent imaging have helped scientists better understand structure and function at the cellular level. Recently, revolutionary advances in imaging technology, GFP, and other live-cell fluorescent probes have allowed cell biologists to quantitatively examine cell structure and function at even higher spatial and temporal resolution. Cell biological assays have become an increasingly important tool in screening and drug discovery. Recognized as the market leader in live cell imaging, Universal Imaging Corporation continues to make exciting advances in this technology. UIC’s new Discovery-1 Cell Based Screening System has evolved from over 18 years experience developing automated microscopy and image analysis technology for cell biology and neurology research. Cell Biological Assays and Screening A dedicated system for rapid automated imaging and image analysis, Discovery-1 makes it easy to incorporate cell biological assays into your screening efforts. Better characterization of your lead compounds with cell-based assays provides greater efficiency on the road to clinical trials. While the Discovery-1 System offers turn-key simplicity and ensures you’ll be up and running your screens in no time, it also has an unmatched level of flexibility to grow as your needs change. Only Discovery-1 has the ability to serve as both a turn-key solution and a platform for developing your future cell biology assays. 2 Our cost-effective hardware solution, system integration, and open-architecture image analysis offer you the most flexibility in this exciting new arena. Sales, Service, and Support in a Complete Package Universal Imaging Corporation and its worldwide representatives provide a total solution to help you analyze your screens. Our direct sales representatives and distributors are continually trained in the latest imaging techniques and are ready to provide you with the best available imaging expertise, advice, onsite training and support. Our in-field representation is considered to be one of the most valued features of the Discovery-1 Cell Based Screening System. In addition to in-field support, we provide extensive training at our in house educational facility known as Universal Imaging Institute. Our Application Scientists help you create analysis protocols and routines designed for your assays and provide training that enables you to develop your own analysis protocols. This extensive support is a major reason more scientists are turning to Universal Imaging Corporation for a cell-based screening solution. UIC’s Discovery-1 Cell Based Screening System is a proprietary opto-mechanical hardware platform and software optimized for the demands of multi-well fluorescence discovery assays. Powered by the award winning MetaMorph® software engine, Discovery-1 has a point and click configuration module to help you set up your screens. Ideal for a multi user environment, the Discovery-1 System can easily store settings for multiple assays and users. The Discovery-1 System supports all standard multiwell formats (24, 96, 384, and 1536 wells) and custom plate configurations. For maximum flexibility, the system can auto-focus for each well, each site within the well and/or for each probe. A high-speed mechanical focus device is used to minimize focusing time and limit photo damage to the specimen. The open architecture of the software allows easy integration with fluidics systems through standard serial or TTL communications. 60x) a wide range of acquisition configurations can be achieved. The imaging platform has a compact footprint (8 x14 inches), suitable for bench top mounting, and the system is compatible with a variety of automated plate loading robots. A 175-watt Xenon arc bulb provides the fluorescence excitation light. The bulb is easy to change, with no focusing required. A full 100% of the light is directed to the camera port through a liquid light guide to provide even illumination across the field of view. Acquisition Optimized for the Demands of Drug Discovery The Discovery-1 System is configured with leading high speed, low light level cameras. A common choice is a 20Mhz high speed, high quantum efficiency interline CCD digital camera with a 1392 x 1040 pixel array and a 6.45-micron pixel size. The Screen Acquisition module of the Discovery-1 System has a point and click design to help you quickly set up your screens. Automated Fluorescence Microscopy At the core of the Discovery-1 System is an imaging platform designed for maximum light throughput and automated fluorescence microscopy. Excitation, emission, and neutral density filter changers allow imaging of 8 different fluorophores per experiment. A high-speed dichroic filter changer (patent pending) optimizes the throughput for each fluorophore with no registration errors. Long working-distance objectives, mounted on a fully automated turret, are suitable for imaging both glass and plastic microtiter plates. With six objectives available (typically from 2x to With its compact footprint, the Discovery-1 System is ideal for bench top mounting and is compatible with a variety of automated plate loading robots. Fluorescence excitation light is provided by a 175-watt Xenon arc bulb rated for 1,000+ hours. 3 Analysis Flexibility Provided by MetaMorph® Software Standard Set of Analytical Routines A dedicated, intuitive image viewer and analyzer in the Discovery-1 System includes a standard set of routines for evaluating your screens. Since your needs may change in the future, the system has the flexibility to create new analysis assays via the analysis tools of the underlying MetaMorph software engine. MetaMorph has been cited in thousands of scientific journal articles and is the acknowledged leader in the market for live cell imaging systems. A comprehensive set of analytical routines is standard with the Discovery-1 System. Current turn-key analysis routines include: • Multi-probe co-localization analysis • Proliferation studies • Cell viability/apoptosis (Live/dead) • Receptor translocation • Neurite outgrowth/Angiogenesis • Cell migration • Cytoskeletal reorganization • Endocytosis/Exocytosis • Protein synthesis, degradation and localization • Cell physiology (Calcium/pH) • Cell signaling and behavior (cells and worms) View image montages by well (shown above), by quadrant, row or even by the entire plate. Using the Discovery-1 System, you can view multiple wells at any zoom and view image montages by well, quadrant, row, or even by the entire plate. With the system’s tools for data retrieval, you can click on an image thumbnail to see the source image in full resolution. Standard graphics features enable you to make color composites to view co-localization of probes, view intensity profiles, place well label and/or analysis results as text on an image and access other visualization tools to aid in hit identification. Cell Counting (Proliferation) Raw data image (DAPI stained nuclei) 4 Cells counted with MetaMorph’s standard area analysis function. Develop your own specialized analysis routines with over 100 functions including spatial, intensity and morphometry. In the example above, the green highlights indicate well values outside the selected range. Raw Intensity Visualization Analysis 3D Intensity Profile Intensity Profile Viewing The bottom intensity profile image shows a 3D perspective of data from both probes used in this experiment. Norak GPCR Assay Using the Discovery-1 System, Norak Biosciences developed this proprietary Transfluor™ assay to target G protein-coupled receptors. The image on the right shows activation of the GPCR. Running the Transfluor assay requires a separate Unstimulated patent license that must be obtained from Norak Biosciences, Inc. (Tel. 919-248-8000) for an additional fee. UIC does not have the right or authority to grant any license under patents covering Transfluor. No license to make, use, sell, offer for sale, or import Transfluor is granted by the purchase of UIC instrumentation or software. (www.norakbio.com) Stimulated 5 Flexibility Open Architecture for Developing Your Own Assays Imaging Model Organisms (C. Elegans Motility Assay) With its open architecture, the Discovery-1 is the only cell-based screening system that gives you the ability to develop your own specialized assays. Over 100 analysis functions (including spatial, intensity and morphometry), user-defined variables, and a wealth of image processing tools including segmentation and deconvolution allow maximum flexibility for future analysis needs. For more exhaustive data analysis, the Discovery-1 System’s open architecture database is compatible with bio-informatics software from major manufacturers. An optional image server is available for high capacity storage and for multi user environments multiple offline analysis stations can be integrated into the system. A01: Acquire Study Kinetics with Time-Lapse Images The Discovery-1 System provides tools for optimizing your assays. When developing your assays, Discovery-1 allows you to study kinetics by taking time-lapse images from one or more sites. These images can then be analyzed to find optimal conditions for dynamic range and reproducibility in your measurements. Hardware Flexibility Discovery-1 can be provided with custom filter sets for use with novel fluorescence probes. Discovery-1 also offers capabilities for control interfaces to fluidics and custom robotics systems. C02: Display/Analyze Adipogenesis Assay Top: nuclei, top right number indicates count of nuclei. Bottom: oil red, top right number indicates lipid measurements normalized to cell number. 6 Robotics/Database Screen Plates Unattended With the Discovery-1’s integrated robotic plate handling system, you can screen multiple, bar-coded plates unattended. UIC Software for the Plate Crane from Hudson Control Group support 60 or 240 plate storage capacity. The Discovery-1 System can also be integrated with custom robotics systems through a generic robotics interface. Supports Microsoft® SQL and is Oracle® Compatible The Discovery-1 database software supports Microsoft SQL and is compatible with Oracle. The suite of functions for database access includes multiple tools for viewing your measurement data interactively linked to your image data. The Discovery-1 database architecture is open and unrestricted for access by other proprietary or commercially available bioinformatics software. Acquired images are stored in the database along with system parameters and barcode information. The Discovery-1 analysis module accesses stored images and returns image analysis results to the database. Using the Discovery-1 viewing module, simple queries can be made to review analyzed images. UIC Software for the Plate Crane from Hudson Control Group support 60 or 240 plate storage capacity. Discovery-1 may also be integrated with other custom robotics and fluidics systems. With Discovery-1’s open architecture and its vast array of functions and tools, the possibilities of cell-based screening are limitless. View Multiple Probes in a Single Color Image Overlay multiple fluorophore images to visually inspect the distribution of each probe. 7 Specifications • High-speed digital cooled CCD camera (Other cameras also available) • Microscope body Custom automated microscope 20 MHz Digitizer 100% light directed to camera port Imaging array – 1392 x 1040 Transmitted light option (Q2-’02) Pixel size – 6.45 microns 14-inch footprint for bench top mounting • High-speed mechanical focus device • 10 Position software-controlled filter wheels Robot compatible • Fluorescence Excitation Light Source 10 Excitation filter positions 175 watt Xenon arc bulb 10 Emission filter positions Long life – 1,000+ hours 10 Neutral Density filter positions Easy bulb swap-out, no focusing required 5 standard filters provided Liquid light guide for even illumination • High-Speed Dichroic Changer (patent pending) Allows for high light throughput • System Expandability Additional Image Storage RAID Server Additional Remote Analysis Stations • Fully automated six-piece objective turret Nikon® Plan Apo and other objectives available Standard options include 2x, 4x, 10x, 20x, 40x, and 60x long working-distance objectives 40x and 60x optimized for glass or plastic microtiter plates • Database Structure Oracle database compatible Microsoft SQL Supported • Freely configurable analysis assays www.discovery-1.com 402 Boot Road Downingtown, PA 19335 Tel: 610-873-5610 • Fax: 610-873-5499 www.universal-imaging.com Domestic US Sales Tel: 610-873-5610 E-mail: sales@universal-imaging.com International Dealers For updated information: www.universal-imaging.com/sales 8