throbber
Preface
`
`About the Documentation
`
`Documentation Overview
`
`familiarize the user with the ThermoFluor® 384 system documentation
`This preface will
`and explains how to use these documents
`
`set
`
`Specifically this preface includes the following sections
`Introduction to ThermoFluor ° 384 System Documentation
`
`Scope of these Documentls
`
`Standard Conventions
`
`Typographical Conventions
`
`Special Terminology
`
`The following table identifies the appropriate section to read in order to learn about specific
`aspects of the documentation set
`
`To learn more about
`
`Read the section
`
`Overview of the ThermoFluor® 384
`
`Introduction to ThermoFluor®
`
`See page
`12
`
`System documentation
`
`Scope of these documents
`
`384 System Documentation
`
`Scope of these Documents
`
`Standard conventions
`
`Standard Conventions
`
`Typographical
`
`conventions
`
`Typographical Conventions
`
`Special terminology
`
`Special Terminology
`
`12
`
`16
`
`16
`
`17
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`01
`May 2001
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`

`

`Preface
`
`ThermoFluor® Instrument Operations
`
`Introduction to ThermoFluoe 384 System
`Documentation
`The ThermoFluor® 384 System Documentation
`is a set of documents covering all aspects of
`the ThermoFluor® 384 system necessary to support executing applications This information
`is organized into four separate documents
`The first document
`ThermoFluor® Instrument Operation described above provides
`basic information on how to install and use the ThermoFluor® 384 System
`ThermoFluor® Analysis Software
`The
`document
`second
`provides
`information on how to use the ThermoFluor® analysis software
`This Software
`provides a powerful way of analyzing the data generated by the ThermoFluor® 384
`System
`ThermoFluor® Applications
`The
`third document
`covers
`the
`ThermoFluor® 384 instrument and Acquire version 30 analysis
`applications in general
`The fourth document
`ThermoFluor® Tutorials is a series of tutorials to help a new
`user learn how to perform common tasks
`These tutorials are arranged in the order of
`increasing complexity They are covered in detail during ThermoFluor® training
`
`basic
`
`use of
`
`the
`
`software
`
`for
`
`4 4
`
`4
`
`4
`
`4 4 4 4
`
`1
`
`These documents
`
`The Scope of these Documents
`are designed with 3 Dimensional Pharmaceuticals
`to
`training class
`someone with background
`and information needed to facilitate
`instructions
`provide
`knowledge in screening to use the ThermoFluor® 384 system They should enable the user to
`perform various tasks and develop an understanding of how the system works
`
`ThermoFluor® 384 System Instrument Operation
`and function of the ThermoFluor® 384
`
`describes the basic construction
`
`This document
`
`system It also describes the installation operation and maintenance of the ThermoFluor® 384
`system In addition it contains background information in the Appendix sections You can
`use this manual when you need information on how to operate the system or to train new
`users of the system
`
`The following table outlines
`the information contained within the Instrument Operation
`section of the documentation and which chapter to refer to for more information
`
`To learn more about
`
`ThermoFluor® 384 System
`
`Instrument specifications
`
`Safety features
`
`Overall system construction
`WindowsTm NT workstation PC
`ThermoFluor® 384 instrument
`
`Plate processing system
`
`Universal power supply
`
`Read
`
`Chapter One Introduction
`
`Chapter Two
`
`Construction and Function
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
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`
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`
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`

`Preface
`
`ThermoFluor® Instrument Operations
`
`Continued from previous nage
`To learn more about
`
`Safety instructions
`
`Site preparation
`
`System installation
`
`Calibration of spots
`
`Acceptance test
`
`Safe operation
`
`Operating software and controls
`Total Control for Windowsm
`ThermoFluor® 384 Acquire 30
`
`ThermoFluor® 384 System operation
`
`System cleaning
`
`Focusing the camera
`
`AddingChanging filters
`
`Replacing the light source
`
`Troubleshooting
`
`Repairs
`
`Read
`
`Chapter Three
`
`Installation and Calibration
`
`Chapter Four
`
`Operation
`
`Instrument Operation Chapter Five
`
`Maintenance
`
`Total Control for Windows Manual
`
`Hudson Group Plate Crane Manual
`
`Consumables List
`
`Appendix A
`Appendix B
`Appendix C
`
`describes
`
`the
`
`This
`
`document
`
`ThermoFluor® Analysis Software
`how to analyze ThermoFluor®
`384 system data using
`ThermoFluor® Analysis Software It describes basic ThermoFluor theory software navigation
`and data analysis It also describes the data exporting batch processing of data and DB sheet
`data browsing You can use this documentation when you need information on how to use
`the ThermoFluor® Analysis Software or to train new users of the system
`
`The following table outlines the information contained within the ThermoFluor® Analysis
`and which chapter to refer to for more information
`Software section of the documentation
`
`To learn more about
`Introduction to the ThermoFluor® analysis
`
`Read
`
`Chapter 1 Introduction
`
`software
`
`The ThermoFluor® analysis software interface
`
`Chapter 2
`
`Getting Started
`
`Starting the application
`
`Opening an intensity file
`
`Automated data analysis
`
`Plate properties
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
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`
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`

`

`Preface
`
`ThermoFluor® Instrument Operations
`
`Continued from previous page
`To learn more about
`
`ThermoFluor
`
`graphical user interface
`
`Menu and toolbar options
`
`Read
`Chapter 3
`
`Navigating Analysis Results
`
`Plate view
`
`Bar chart view
`
`Plot view
`
`Layout table
`
`Results table
`
`Summary table
`
`Averaging replicates
`
`Modifying analysis settings
`
`Specifying reference wells
`
`Excluding data points
`
`Manual data analysis
`
`Saving into a file
`
`Uploading into the database
`
`Exporting into a text file
`
`Printing
`
`Copying views and tables
`
`Batch analysis
`
`Batch registration
`
`Connect
`
`Requery plate info
`
`Edge detection
`
`Dropout detection
`
`Chapter 4
`
`Customizing Analysis
`
`Chapter 5
`
`Output Options
`
`Chapter 6
`Miscellaneous Options
`
`Appendix A
`Dropout and Edge Detection
`
`ThermoFluor® Applications Guide
`This document provides fundamental
`associated with the
`information for basic applications
`ThermoFluor® 384 system It describes the basics of protein preparation and high thruput
`screening HTS It also describes some general data analysis methods You can use this
`document when you need information on these applications with regard to the ThermoFluor®
`384 system or to train new users of the system
`
`The following table outlines the information contained within the ThermoFluor® Applications
`Guide of the documentation and which chapter to refer to for more information
`
`Copyright © 2001 3Dimensiona1 Pharmaceuticals Inc
`Confidential
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`04
`May 2001
`
`4
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`
`

`

`Preface
`
`ThermoFluor® Instrument Operations
`
`To learn more about
`
`Overview of ThermoFluor® applications guide
`
`Read
`
`Chapter 1
`
`Introduction
`
`ThermoFluor® GLPs
`
`Basic theory behind ThermoFluor®
`
`Introduction to ThermoFluor® optimization
`
`Condition optimization
`
`Process optimization
`
`Positive Controls
`
`Secondary Confirmations
`
`Chapter 2
`Optimizing ThermoFluor® Conditions
`
`Introduction to ThermoFluor® High Throughput
`
`Chapter 3
`
`Screening
`
`High Throughput Screening
`
`ThermoFluor High Throughput Screening
`
`ThermoFluor® 384 assay setup
`
`High Throughput Screening
`
`Maintenance and Quality Assurance
`
`Introduction to data analysis
`
`Hit selection
`
`Hit qualification
`
`Hit re testing
`
`Secondary assays
`
`Chapter 4
`
`General Data Analysis
`
`ThermoFluor® Tutorials
`This document provides procedures and exercises for common tasks associated with the
`ThermoFluor® 384 system It
`tutorials on protein characterization
`sample
`includes
`It also includes validation and optimization tutorials You
`preparation and data collection
`can use this manual when you need information on these common tasks with regard to the
`ThermoFluor® 384 system or to train new users of the system
`
`The following table identifies the common tasks described in the ThermoFluor® Tutorials of
`the documentation and which Tutorial to refer to for practice in performing a given task
`
`To learn more about
`
`Preparing the assay plate
`
`Read
`
`Tutorial One
`
`Initial Protein Screen
`
`Setting up and running the assay plates
`
`Analyzing the assay plate data
`
`Viewing the analysis results
`
`Determining the best concentration mode and
`
`dye
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
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`

`

`Preface
`
`ThermoFluor° Instrument Operations
`
`4
`
`4
`
`Continued from previous page
`To learn more about
`
`Preparing the assay plate
`
`Setting up and running the assay plates
`
`Analyzing the assay plate data
`
`Viewing the analysis results
`Determining the best pH buffer and salt
`
`concentrations
`
`Preparing the assay plate
`
`Setting up and running the assay plates
`
`Analyzing the assay plate data
`
`Determining existence of irregularities or
`
`systematic errors
`
`Preparing the assay plate
`
`Setting up and running the assay plates
`
`Analyzing the assay plate data
`
`Initial
`
`identification of potential hits
`
`Select hits
`
`Qualify hits
`
`Preparing the uniform plates
`
`Setting up and running the accuracy test
`
`Setting up and running the accuracy test
`
`Analyzing the assay plate data
`
`Verifying data quality
`
`Read
`
`Tutorial Two
`
`BufferSalt Screen
`
`Tutorial Three
`
`Uniform Plate Screen
`
`Tutorial Four
`
`Compound Library Screen
`
`Tutorial Five
`
`Select and Qualify Hits
`
`Tutorial Six
`
`Screening Libraries
`
`Standard Conventions
`To make the documentation
`easy to read the manuals use standard guidelines or
`In other words formatting for specific items within the text will always be
`conventions
`presented in the same way For example software dialog box names are printed in Tahoma
`font and all caps such as the OUTPUT FILE dialog box
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`06
`May 2001
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`
`4
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`

`

`Preface
`
`ThermoFluor® Instrument Operations
`
`Typographical Conventions
`The documents use the following typographical
`software applications
`
`conventions
`
`for the analysis and control
`
`Item
`
`Menu name
`
`Toolbar name
`
`Menu command
`
`Toolbar buttons
`
`Dialog box name
`
`Depicted as
`Tahoma font all caps bold
`Tahoma font all caps bold
`
`Tahoma font initial cap bold
`Tahoma font initial cap bold
`Tahoma font all caps
`
`Dialog box field name
`
`Text entry
`
`Keyboard keys
`
`Tahoma font initial cap
`Courier PCL6 font
`Tahoma font initial cap en
`closed in <>
`
`For example
`
`The FILE menu
`The PAGER toolbar
`The Open file command
`The Selection button
`
`Type the desired file name in the
`PRINT dialog box
`Number Of Copies
`Enter the file name Batch int
`
`Press and hold the <Ctrl> and
`
`<Shift> keys
`
`Special Terminology
`The following table provides definitions for some of
`ThermoFluor®
`
`the terms used in conjunction with
`
`Term
`
`Hit
`
`intINT filee
`
`psqPSQ file
`
`tfTF file
`
`Definition
`A well on a screening plate that exhibits a signal strength that
`exceeds the Tm shift threshold set as a significant response for
`the run
`File created by the ThermoFluor® Acquire 30 application which
`
`contains integrated intensity values for wells in a plate
`File that contains raw camera exposure data The ThermoFluor®
`Acquire 30 application creates int integration files from the
`psq files that correspond to the replicate exposures for a well
`The ThermoFluor® Analysis Software creates this file It
`
`contains the fitted data along with other values that are calculated
`andor downloaded from a data base for each well on a plate
`
`The table below lists common acronyms that are used in conjunction with ThermoFluor®
`
`Acronym
`TCW
`
`Definition
`
`Total Control for Windows program developed by Hudson
`Control Group
`
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`Confidential
`
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`

`

`4
`
`4 4 4 4
`
`4 4
`
`4 4 4
`
`4 4
`
`4 i
`
`i
`
`4 4
`
`4 4 4
`
`Preface
`
`ThermoFluor® Instrument Operations
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`08
`May 2001
`
`Artisan Scientific
`
`Quality Instrumentation
`
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`
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`
`

`

`Table of Contents
`
`CHAPTER ONE
`
`Introduction
`Overview
`Introduction to the ThermoFluor® 384 System
`Instrument Specifications
`Safety Features
`
`CHAPTER TWO
`
`Construction and Function
`Overview
`
`Overall Construction
`Windows Tm NT Workstation
`ThermoFluor® 384 Instrument
`
`Plate Processing System
`Universal Power Supply
`
`CHAPTER THREE
`
`Installation and Calibration
`Overview
`
`Safety instructions
`
`Site preparation
`System installation
`Calibration of Spots
`Acceptance Tests
`
`CHAPTER FOUR
`
`Operation
`Overview
`
`Safe Operation
`Operating Software and Controls
`Total Control for WindowsTm
`ThermoFluor® 384 Acquire 30
`ThermoFluor® 384 System Operation
`
`CHAPTER FIVE
`
`Maintenance
`Overview
`
`System Cleaning
`Camera Focusing
`Filter Changes
`Light Source Changes
`
`Troubleshooting
`
`Repair
`
`11
`
`11
`11
`12
`14
`15
`
`21
`
`21
`21
`22
`23
`24
`29
`212
`
`31
`
`31
`31
`32
`33
`38
`315
`319
`
`41
`
`41
`41
`42
`43
`410
`418
`429
`
`51
`
`51
`51
`52
`53
`55
`57
`58
`517
`
`Copyright © 2001 3Dimensional Pharmaceuticals Inc
`Confidential
`
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`May 2001
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`

`

`4
`
`4
`
`4
`
`4
`
`4 4 4 4
`
`4 4 4 4 4 4 4
`
`4
`
`4
`
`4 4 4
`
`4 4 4
`
`4
`
`4
`
`4
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`010
`May 2001
`
`Artisan Scientific
`
`Quality Instrumentation
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`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`BioRad Exhibit 2009
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`
`

`

`Chapter One
`
`Introduction
`
`Overview
`
`This chapter will
`features
`
`familiarize the user with the ThermoFluor® 384 system and its safety
`
`Specifically this chapter includes the following sections
`
`Introduction to the ThermoFluor°384 System
`
`Instrument Specifications
`
`Safety Features
`
`The following table identifies the appropriate section to read in order to learn how to perform
`a specific task
`
`To learn more about
`
`ThermoFluor® 384 system
`
`Instrument specifications
`
`Safety Features
`
`Read the section
`
`Introduction to
`
`ThermoFluor® 384 System
`
`Instrument Specifications
`
`Safety Features
`
`See page
`1 2
`
`14
`
`15
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`11
`May 2001
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`
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`
`

`

`4 4 4 4 4 4
`
`4 4 4 4 4 4 4 4 4
`
`4 4
`
`4
`
`41
`
`41
`
`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`Introduction to the ThermoFluor® 384 System
`The ThermoFluor® 384 system performs miniaturized fluorescence based thermal shift assays
`The ThermoFluor® screening
`for the high throughput screening of compound libraries
`strategy has several advantages over the more conventional HTS methodologies the most
`relies on a general physical process common to most if not all
`important of which is that
`The
`and their ligand bound complexes
`thermal unfolding of biomolecules
`drug targets
`ThermoFluor® instrument measures dye fluorescence in the presence of a protein As the
`protein unfolds its hydrophobic parts are exposed which creates an environment
`that causes
`The more the protein
`unfolds
`the dye to fluoresce
`the intensity of the
`the greater
`fluorescence
`
`it
`
`Figure 1 1 The thermal unfolding of the protein allows the dye to enter a
`more hydrophobic environment and fluoresce
`
`the proteins melting transition can be measured More importantly for the
`In this manner
`ThermoFluor® screening strategy the effects of ligand binding on the proteins melting
`transitions can be measured
`See the Application Manual
`for more details on the theory
`behind ThermoFluor®
`
`Figure 12 Ligand binding shifts the unfolding temperature of the protein
`Copyright © 2001 3Dimensiona1 Pharmaceuticals Inc
`Confidential
`
`12
`May 2001
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`

`

`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`The ThermoFluor® 384 system provides a flexible and modular fluorescence assay system
`with an automated robotic microplate loading system to perform this function The basic
`ThermoFluor® 384 system is capable of sequentially loading and unloading up to twenty 20
`384 well
`The ThermoFluor® 384 system works in conjunction
`thermal cycler microplates
`for WindowsTM
`and 3 Dimensional
`with a personal
`running Total Control
`computer
`ThermoFluor® Acquire 30 control software under Microsoft WindowsTM
`Pharmaceuticals
`NT
`
`The robotic microplate handler PlateCraneTM by Hudson Control Group moves sample
`As the
`plates from an input storage magazine to the imaging area of the instrument
`microplate is removed from the input magazine a barcode reader
`reads the plates bar code
`identification number Once the microplate is in the imaging area the ThermoFluor® control
`software initiates a ThermoFluor® experiment on the microplate When the experiment
`is
`completed the robotic handler
`then retrieves the plate from the imaging area and places it
`into an output storage magazine This process is repeated for up to 20 microplates
`in a single
`session The PlateCraneTM robot and plate storage magazines stacks are optimized to handle
`a specified brand and model 384 well PCR plates
`
`Once the data have
`the 3 Dimensional
`been collected
`Pharmaceuticals
`analysis software is used to analyze the data to determine melting temperatures and identify
`hits
`
`ThermoFluor®
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
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`

`

`4
`
`4 4
`
`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`Instrument Specifications
`
`This section gives the specifications of the ThermoFluor® 384 system and the conditions
`necessary for it to function properly
`
`Overall System Specifications
`Height H
`Width W
`Depth D
`
`65
`24
`36
`
`Weight
`
`Table Top
`Control Cabinet
`
`160 lbs
`300 lbs
`
`Environmental Conditions
`
`1575 mm
`610 mm
`915 mm
`
`73 kg
`136 kg
`
`Storage Temperature
`Storage Humidity
`
`Operation Temperature
`Operation Humidity
`
`40 C
`20
`20 80
`20° 24° C
`relative non condensing
`30 50
`
`Power Supply Ratings
`
`Line Voltage
`Frequency
`Power
`
`Windows Tm NT workstation
`
`110 VAC +110
`60 Hz +110
`15 A
`Properly grounded outlet
`
`HewlettPackard Vectrarm Pentium ER 300 MHz or better 128 MB RAM hard disk with
`100 GB or better
`SVGA monitor with 800 x 600 resolution
`3 12 floppy disk drive
`CDROM
`250 MB Iomega ZIPTM Drive
`2 available PCI slot one for camera card and one for Rocketporum serial expansion card
`Microsoft Windows Tm NT 40 with Service Pack 60
`
`4 4
`
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`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
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`
`

`

`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`Safety Features
`
`The ThermoFluor® 384 system should be setup and run by 3 Dimensional Pharmaceuticals
`factory trained immediately contact 3
`Inc factory trained personnel only If you are not
`Dimensional Pharmaceuticals Inc by email at en gsupport3dpcom to schedule training
`
`This Operating Manual
`contains information and procedures for the safe installation and
`operation of the ThermoFluor® 384 system Before installing or running the ThermoFluor®
`384 system completely and thoroughly review the latest version of this document
`If any
`to you immediately
`unclear
`3 Dimensional
`instructions
`are
`or unfamiliar
`contact
`by email at engsupport3dpcom for clarification and proper
`
`Pharmaceuticals
`
`Inc
`
`operation
`
`Abnormal instrument operation should be immediately noted and instrument use discontinued
`until examined by a representative from 3 Dimensional Pharmaceuticals Inc
`
`follow all standard operating procedures and policies An
`As with all
`laboratory equipment
`operations and maintenance logbook should be maintained at the instruments location
`
`Handle with Care
`To avoid equipment damage handle components carefully Handle the CCD Camera with
`particular care as it
`
`is fragile
`
`Lift Properly
`lifting techniques when lifting shipping containers and system components Four
`Use proper
`4 persons positioned at each corner should be used when lifting the system stand and the
`
`instrument base plate
`
`Electrical
`
`Ensure the systems universal power supply is unplugged and that all power switches are in
`the OFF position before performing maintenance
`
`Use an ESD electrostatic
`strap and discharge cable per
`discharge wrist grounding
`manufacturers instructions during all signal cable connections
`to avoid damage to the
`equipment by static electricity
`
`UV light
`Avoid looking directly into UV light source as it may cause damage to the eye
`
`Labeling
`Warning labels are located on the instrument to avoid potential dangerous situations to an
`lab personnel using the ThermoFluor® 384 instrument Normal operational
`operator or other
`labels are provided to clarify function of the various indicator lights switches and electrical
`Each label
`connections used in normal operations
`its location and a brief description of the
`instrument operation associated with the label are listed below
`
`Copyright 0 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`15
`May 2001
`
`BioRad Exhibit 2009
`IPR201700055
`Page 15 of 116
`
`

`

`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`Light Tight Front Access Door Label
`front access door of the ThermoFluor®
`This label
`is located above the light tight compartment
`384 instrument
`This door provides access to the light
`
`tight compartment
`
`for plate loading
`
`4
`
`4
`
`4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4
`
`and unloading
`
`THE FRONT ACCESS DOOR IS NOT INTERLOCKED Never open the front
`access door when the system active light
`is illuminated during a sample run
`r or when power is first applied to the instrument
`
`This door should only be open when plates are being loaded and unloaded from the
`
`Plate Processing Area Warning Area Label
`This label
`front access door of the ThermoFluor®
`is located above the light tight compartment
`384 instrument
`This door provides access to the light
`and unloading
`
`tight compartment
`
`for plate loading
`
`Never
`
`reach into the access door or place any items into the access door
`
`Normal operation should never require reaching through the access door
`into the light tight
`compartment Such action is hazardous and can result in injury or damage to the instrument
`
`Manufacturers Serial Plate Label
`
`in located on the right side of the ThermoFluor® 384 instrument
`These
`This
`label
`connections should be made with no power applied to either the computer or the instrument
`In addition there is labeling for the power entry module 110 VAC 60 Hz ONLY Use
`10A 250 VAC SloBlo Fuses only
`
`Provide only 110 VAC 60 Hz singlephase electrical
`Other
`connection
`operating voltages and frequencies may cause damage to the instrument and
`or unexpected system performance
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`16
`May 2001
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`BioRad Exhibit 2009
`IPR201700055
`Page 16 of 116
`
`

`

`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`LXTh
`
`0
`
`0
`
`A ground stud label
`instrument panel
`
`is also provided to indicate the ground stud located on the side
`
`PlateCraneTM Label
`
`indicating its DB9 serial control
`Labels are located on the side of the PowerCraneTM
`connection AC power connection and manufacturers serial number
`
`Bar Code Reader Label
`Labels are located on the side of the Bar Code Reader
`connection and power connection
`
`indicating its DB9 serial control
`
`Ground Labels
`Ground labels are located throughout
`connection point
`
`the instrument These labels indicate a chassis ground
`
`Electrical Warning Labels
`Electrical warning labels are located on the back instrument panel and inside the instrument
`There are no user serviceable parts in this panel and opening this panel can expose the user
`to unsafe voltages
`
`Copyright © 2001 3Dimensiona1 Pharmaceuticals Inc
`Confidential
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`17
`May 2001
`
`BioRad Exhibit 2009
`IPR201700055
`Page 17 of 116
`
`

`

`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`Plate Processing Labels
`labels are best viewed from the top of the instrument Specifically plate
`orientation labels and input
`output stack labels
`
`Several additional
`
`PlateCraneun
`robotic arm
`
`Stackl
`
`input
`magazine
`
`Stack2 output
`magazine
`
`The plate orientation label
`
`locates well Al on each plate placed in the instrument
`
`Connections
`The ThermoFluor® 384 instrument CCD camera SCSI connection
`and controller serial
`connection should be made with no power applied to either the computer or the instrument
`Similarly the plate processing PlateCraneTM and bar code reader cables should be connected
`with no power applied to either the computer or the instrument The UPS inside the workcell
`must be turned off even if no external power is applied
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`18
`May 2001
`
`4
`
`BioRad Exhibit 2009
`IPR201700055
`Page 18 of 116
`
`

`

`Introduction
`
`ThermoFlour® 384 Operating Manual
`
`Chapter Two
`Construction and Function
`
`Overview
`
`familiarize the user with the construction of the ThermoFluor® 384 system
`This chapter will
`and the function of its major components
`
`Specifically this chapter will include the following sections
`
`Overall system construction
`
`Windows TM NT workstation PC
`
`ThermoFluor ° 384 instrument construction
`
`Plate processing system construction
`
`The following table identifies the appropriate section to read in order to learn more about the
`construction of the ThermoFluor® 384 system
`
`To learn more about
`
`Overall system construction
`Windows Tm NT workstation PC
`ThermoFluor® 384 instrument construction
`
`Read the section
`
`Overall Construction
`
`WindowsTmNT Workstation
`
`ThermoFluor®384
`
`Instrument
`
`Plate processing system construction
`
`Plate Processing System
`
`See page
`22
`23
`24
`
`29
`
`Copyright © 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88SOURCE I wwwartisanscientificcom
`
`21
`May 2001
`
`BioRad Exhibit 2009
`IPR201700055
`Page 19 of 116
`
`

`

`4
`
`4 4
`
`4 4
`
`4 4 4
`
`4 4 4 4 4 4 4 4 4 4 4 4 4 4
`
`4 4 4
`
`4 4
`
`Construction and Function
`
`ThermoFlour® 384 Operating Manual
`
`Overall Construction
`
`The ThermoFluor® 384 system is a flexible and modular fluorescence assay system with an
`automated plate processing system The basic ThermoFluor® 384 system is capable of
`sequentially loading and unloading up to twenty 20 384 well
`thermal cycler microplates
`The ThermoFluor® 384 instrument works in conjunction with a WindowsTm NT workstation
`ThermoFluor® Acquire 30 control
`running 3 Dimensional
`Pharmaceuticals
`software to
`perform the fluorescence assay The plate processing system has a PlateCraneTM robotic arm
`that moves sample plates from an input storage magazine to the imaging area of the
`instrument after which the ThermoFluor® Acquire 30 control software program initiates a
`ThermoFluor® experiment on the microplate When the experiment is completed the Plate
`into an output magazine The
`Crane retrieves the plate from the imaging area and places it
`various components or the system are powered by a universal power supply
`
`Plate
`
`Processing
`System
`
`ThermoFluor® 384
`Instrument
`
`WindowsTM NT
`Workstation
`
`Universal Power
`
`Supply
`
`Figure 2 1 The ThermoFluor® 384 system
`
`Copyright 0 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`22
`May 2001
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`BioRad Exhibit 2009
`IPR201700055
`Page 20 of 116
`
`

`

`Construction and Function
`
`ThermoFlour® 384 Operating Manual
`
`Windows TM NT Workstation
`The WindowsTM NT Workstation
`contains the software that controls the operation of the
`The
`system and creates data files that are analyzed by the ThermoFluor® analysis software
`ThermoFluor® analysis software is usually installed on a separate analysis workstation The
`ThermoFluor® analysis software will be discussed in the ThermoFluor® Analysis Software
`Total Control for WindowsTM TCW operates the overall system and allows the
`Manual
`It directly operates the plate processing system and it
`running of multiple plates
`indirectly
`operates the ThermoFluor® 384 instrument through the ThermoFluor® Acquire 30 control
`software The ThermoFluor® Acquire 30 control software interfaces with a CCD camera and
`an embedded controller in the ThermoFluor® 384 instrument
`The ThermoFluor® Acquire
`the use of TCW or
`30 control
`software can be used to run a single plate without
`the
`PlateCraneTM robotic arm The software relationships are illustrated below
`
`WindowsTmNT Workstation
`
`Total Control for
`Window
`
`ThermoFluor®
`Acquire 30
`
`os311070
`
`Analysis
`Workstation
`
`ThermoFluor®
`Analysis Software
`
`PlateCrajnem4
`
`CCD Camera
`
`Embedded Controller
`
`Plate Processina System
`
`TherrnoFluor®384 Instrument
`
`Figure 22 Windows Tm NT Workstation software applications
`
`Total Control for WindowsTM
`
`This software controls the PlateCraneTM robotic arm movements and interfaces with the bar
`The method that
`is used to move the microplates
`code reader
`from the input storage
`magazine to the imaging area then to the output magazine is programmed
`using this
`The program also interacts with the ThermoFluor® Acquire 30 control software
`application
`to coordinate actions between the ThermoFluor® 384 instrument and the Plate Processing
`system Refer to Appendix A for details
`ThermoFluor® 384 Acquire 30
`The ThermoFluor® Acquire 30 control
`provides
`ThermoFluor® 384 system This software allows the user to enter run parameters that are
`sent to the embedded controller that operates the instrument components
`It also initiates the
`The
`experiment and allows the user to designate where the resulting data will be saved
`details of this program and its user interface will be discussed in Chapter 4 Operation
`Copyright C 2001 3 Dimensional Pharmaceuticals Inc
`Confidential
`
`for
`
`the
`
`23
`May 2001
`
`software
`
`the user
`
`interface
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`BioRad Exhibit 2009
`IPR201700055
`Page 21 of 116
`
`

`

`4
`
`4 4 4
`
`1
`
`4 4
`
`4 4
`
`4
`
`4 4 4 4 4 4
`
`4
`
`4 4
`
`Construction and Function
`
`ThermoFlour® 384 Operating Manual
`
`ThermoFluoe 384 Instrument
`The ThermoFluor® 384 Instrument actually performs the fluorescence assays It consists of
`three compartments These are the
`
`Optical compartment
`
`Light tight compartment
`
`Power and control
`
`compartment
`
`Optical Compartment
`The optical compartment contains the
`optical components that measure the
`These include the CCD camera
`fluorescence
`lens and filter wheel This compartment
`accessible by the user in order to change filters
`
`is
`
`Figure 23 Back of ThermoFluor® 384
`
`Instrument
`
`CCD Camera
`The CCD camera records the plate fluorescence images
`is a Roper Scientific camera
`The CCD camera comes with its
`model Sensys 0400 It has a halfinch mega pixel format
`own power supply that
`and plugged into the system
`is located in the optical compartment
`Universal power supply Refer to the Photometrics SenSys User Manual Advanced Camera
`Operation Manual and Software Guide Manual for more details
`
`It
`
`11111
`
`I
`
`I
`
`11111i111
`
`f
`
`I
`
`4
`
`Figure 24 CCD camera mounted in instrument
`
`CAUTION The camera should never be connected or removed from a live
`power cable This could damage the cameras electronic components Verify
`the cameras power supply is switched OFF and unplugged from the Universal
`Power Supply before disconnecting its power cable
`
`Copyright © 2001 3 Dimensional Pharmaceuticals
`Confidential
`
`Inc
`
`24
`May 2001
`
`Artisan Scientific
`
`Quality Instrumentation
`
`Guaranteed 1888 88 SOURCE I wwwartisanscientificcom
`
`BioRad Exhibit 2009
`IPR201700055
`Page 22 of 116
`
`

`

`Construction and Function
`
`Th

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