OligoProcess - GE Healthcare Life Sciences
Contents
1. This symbol indicates that the waste of electrical and electronic equipment must not be disposed as unsorted municipal waste and must be collected separately Please contact an authorized representative of the manufacturer for information concerning the decommissioning of your equipment When the system has reached the end of its life cycle it should be handled according to current laws and regulations regarding environmental aspects of recycling and disposal of industrial equipment This is the responsibility of the end user Contact your local authorities if you have any questions regarding the environmental aspects or the laws in force for recycling or disposing of industrial equipment of this type OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview 3 System overview This chapter contains an overview of the components in OligoProcess 3 1 System layout The system layout is shown in the Assembly drawings included in the system documentation 3 2 System flow path The figure below from System Control in UNICORN shows the positions of the components and pipes in OligoProcess system flow path Note In this manual the components are designated according to GE Healthcare standards A cross reference list for the local designations can be found in the system documentation RUO ees RVO36 HOSS oe ACN_1 trocken Fig 3 1 System flow path 3 2 1 Piping and flange types All piping in O2. Biosciences UK Ltd Amersham Place Little Chalfont Buckinghamshire HP7 9NA UK GE Healthcare Amersham Biosciences Corp 800 Centennial Avenue P O Box 1327 Piscataway NJ 08855 1327 USA GE Healthcare Amersham Biosciences KK Sanken Bldg 3 25 1 Hyakunincho Shinjuku ku Tokyo 169 0073 Japan Asia Pacific Tel 852 2811 8693 Fax 852 2811 5251 e Australasia Tel 61 2 9899 0999 Fax 61 2 9899 7511 e Austria Tel 01 57606 1619 Fax 01 57606 1627 Belgium Tel 0800 73 888 Fax 03 272 1637 Canada Tel 800 463 5800 Fax 800 567 1008 e Central East amp South East Europe Tel 43 1 982 3826 Fax 43 1 985 8327 e Denmark Tel 45 16 2400 Fax 45 16 2424 e Finland amp Baltics Tel 358 0 9 512 39 40 Fax 358 0 9 512 39 439 e France Tel 01 69 35 67 00 Fax 01 69 41 96 77 e Germany Tel 0761 4903 490 Fax 0761 4903 405 e Italy Tel 02 27322 1 Fax 02 27302 212 e Japan Tel 81 3 5331 9336 Fax 81 3 5331 9370 e Latin America Tel 55 11 3933 7300 Fax 55 11 3933 7304 e Middle East amp Africa Tel 30 210 9600 687 Fax 30 210 9600 693 Netherlands Tel 0165 580 410 Fax 0165 580 401 Norway Tel 815 65 555 Fax 815 65 666 e Portugal Tel 21 417 7035 Fax 21 417 3184 e Russia amp other C l S amp N I S Tel 7 095 232 0250 956 1137 Fax 7 095 230 6377 e South East Asia Tel 60 3 8024 2080 Fax 60 3 8024 2090 Spain Tel 93 594 49 50 Fax 93 594 49 55 e Sweden Tel 018 612 1900 Fax 018 612 1910 Switzerland Tel 084
3. Pressure control valve The pressure control valve PCV 341 is used to pneumatically control the backpressure in the system At low flow rates during the synthesis the valve raises the backpressure in order to maintain a good distribution in the column At high flow rates for example during the wash procedure the valve decreases the backpressure The valve is connected between the conductivity cell and outlet valve XV 061 Fig 3 9 Pressure control valve 3 13 Containers for reagents and solvents Containers for reagents and solvents are not included in the system at delivery Always use appropriate types of stainless steel containers Make sure that the containers are properly grounded OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 29 System overview 3 14 Junction box The junction box is placed outside the process room and does not need to be EX classified All cables for power supply communication with the computer and other external equipment are routed through the junction box The power and signal cables between the junction box and the process cabinet are bundled and ExX protected Mains switch Purge completed indicator Fig 3 10 Junction box The front panel of the junction box is equipped with a switch and status indicator as described in Table 3 2 Indicator Switch Color Description POWER Turns on off the mains power to the entire switch system junction box process cabinet
4. V Biosciences SYSTEM NO 1706 YEAR OF MANUFACTURE 2005 SUPPLY VOLTAGE FREQUENCY MAX CURRENT CONSUMTION MAX CURRENT REQUIREMENT MAX PROCESS PRESSURE PROTECTION CLASS PNEUMATIC SUPPLY MIN MAX MIN PURGE FLOW MIN AMOUNT OF PURGE AIR MIN PURGE TIME INTERNAL FREE VOLUME MIN PURGE OPERATING PRESS MAX PURGE OPERATING PRESS AMBIENT TEMPERATURE 136 EEx nZ 14 RWT V 9 05 ATEX 0091X Fig 2 1 ID and rating label on OligoProcess OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 13 Safety instructions as 2 4 3 Other labels on the system The following safety labels are on the system IMPORTANT Before service maintenance or return to Amersham Biosciences clean the equipment and accompany it with a decontamination statement specifying substances with which it has been in contact during use and the method of cleaning 14 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Safety instructions 2 5 Intended use of OligoProcess OligoProcess is intended for production of DNA and RNA oligonucleotides The system must be used in accordance with the safety instructions and technical specifications given in this Guide to Safe Operation and the system documentation OligoProcess must not be used for any other purposes or in any other way than described in the documentation supplied with the system 2 6 General safety precautions This section specifies general safety precautio
5. a fouled sensor relay and has automatic temperature compensation The transmitter mounted close to the sensor is the signal interface between the sensor and the controller in the process cabinet The conductivity sensor CE 101 is placed after the column in the flow path Fig 3 4 Conductivity cell 3 7 UV monitor There are two UV flow cells in OligoProcess one before AE 131 and one after the column AE 132 The UV monitor is a multi wavelength UV Vis monitor that uses advanced fiber optic technology with high sensitivity at up to three wavelengths simultaneously in the range 190 700 nm The use of optical fibers together with a unique flow cell design ensures a high signal to noise ratio with a minimal drift and refractive index effects The wavelength can be changed using the UNICORN software during a run either from the method or by manual instructions OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview ss The optical pathlength 2 mm is set with shim plates Fig 3 5 UV cell 3 8 Pressure monitor The pressure before the column is continuously monitored by a pressure sensor PIT 111 It is a ceramic sensor with the process pressure acting directly on the ceramic membrane A transmitter integrated in the module handles the communication with the controller in the process cabinet Fig 3 6 Pressure sensor OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 27 System ove
6. application and the environment in which the system is operated In order to secure the safe operation of the system you should perform a risk assessment This assessment results in safety instructions for installation operation and maintenance use of proper personal protective equipment or other arrangements needed to operate the process safely The instructions should be used together with the general descriptions and instructions given in the system documentation and in this Guide to Safe Operation 2 2 Safety compliance OligoProcess is an EX classified system that complies with the requirements of ATEX 94 9 EC a safety directive for equipment and protective systems intended for use in potentially explosive athmospheres The compliance with the directive is valid only under the condition that OligoProcess is installed operated and maintained according to the system documentation and this Guide to Safe Operation That includes general safety precautions as well as specific EX related precautions as described in this guide Any equipment connected to OligoProcess must meet the requirements of the ATEX 94 9 EC or other equivalent international safety standard 2 2 1 EX classification The classification of OligoProcess is only valid when it is used according to the EX related safety instructions in this and the subsequent chapters Area classification The environment where OligoProcess is used is classified as zone 2 An explosive atmo
7. computer PURGE Yellow The light is turned on after purging of the indicator process cabinet The light is turned off during operation if the purging system fails to keep the pressure in the process cabinet above the specified overpressure Table 3 1 Switches and indicators on the junction box 30 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview i 3 15 Process cabinet The process cabinet in the process system contains all power and control electronics needed for controlling and monitoring the components in the process system The cabinet also has a purging system which prevents flammable gases from entering the cabinet or the UV monitor enclosing The power and signal cables are connected to the junction box and are Ex protected Bypass key Mains switch Run switch Cabinet pressure manometer Purge air Power on h indicator supply inlet Instrument Continue air supply Pause inlet Emergency stop Fig 3 11 Process cabinet 3 15 1 Cabinet purging system OligoProcess has a pressurized process cabinet which prevents flammable gases from entering The UV monitor enclosing is also a part of the pressurized cabinet connected by an air duct The overpressure is produced by compressed air and a purging system inside the cabinet which controls the air flow A pressure regulator controls the inlet air pressure The air then flushes through the cabinet the air duct and the UV SSS Ol
8. container 1 Usea clean and dry container 2 Fill the container with inert gas argon nitrogen 3 Add solvent solvents 4 Add the solid powder amidites activator thiolation reagent 5 Agitate until everything is mixed and or dissolved SSS 44 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Synthesis preparation 6 6 2 Packing the column Make sure that the column used fulfills the pressure and flow rate specifications stated in the system documentation WARNING All users must read the instructions supplied with column especially the safety instructions to fully understand the safe use of the column WARNING OVER PRESSURE e Make sure that the column withstands the expected operating pressures e Never block the outlet tubes because this will create over pressure and might result in injury WARNING EXPLOSION HAZARD Always use inert gas when packing the column flushing solvents out of the system and before filling the system with solvents Otherwise air might enter the flow path and create an explosive atmosphere when being mixed with vaporized solvent WARNING EXPLOSION HAZARD Avoid discharge from static electricity in potentially explosive atmospheres Make sure that the system including the column is connected to the plant grounding network 6 3 Connecting the column WARNING EXPLOSION HAZARD Always use self closing quick connectors to avoid leakage at the co
9. during the run e Check that the compressed air supply to the purge system is connected and has sufficient capacity and pressure OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 47 Operation 48 7 4 Starting a run See the UNICORN user manuals for instructions on starting a synthesis run 7 5 During a run See the UNICORN user manuals for instructions on viewing a run and customizing the view panes 7 6 Viewing and printing the result See the UNICORN user manuals for instructions on viewing and printing the result 7 7 After a run and storage WARNING EXPLOSION HAZARD After closing down the system make sure that the rear door is closed until the temperature of the components has decreased and reached a level of the temperature class of the system WARNING EXPLOSION HAZARD Always use inert gas for flushing solvents out of the system and before filling it with solvents Otherwise air might enter the flow path and create an explosive atmosphere when being mixed with vaporized solvents 7 7 1 Cleaning between runs The flow path should be flushed with acetonitrile after each run 7 7 2 Storage The flow path should be left filled with acetonitrile if the system will not be used for a few days or longer OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Maintenance ex 8 Maintenance This chapter provides instructions for routine component maintenance and a maintenance s
10. might be affected 2 9 2 Restart procedure 1 Check that the external compressed air supply is turned on 2 Check that the manual valves for purge air and instrument air on the process cabinet are turned on Sy OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 21 Safety instructions 22 3 Turn on the mains power switch on the junction box Result The process cabinet is purged When successfully finished the PURGE indicator on the junction box is turned on 4 Turn on the power switch on the process cabinet 5 Connect UNICORN to the process system 2 10 Cabinet purging system OligoProcess has a pressurized process cabinet which prevents flammable gases from entering the cabinet during normal operation During start up the purging system removes any flammable gases from the cabinet If the purging system fails maintaining the specified overpressure in the cabinet the power supply to the process system is automatically turned off For more information on the purging system see section 3 15 1 Cabinet purging system 2 11 Chemical resistance CAUTION Always make sure that the column media columns and wetted parts of the system are compatible with reagents and solvents at the concentration time and temperatures used All materials in wetted parts have been selected in order to withstand the chemicals in the process The system documentation lists all materials used 2 12 Recycling and disposal
11. on CU 950 indicate communication error on the displays OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Safety instructions ee e When the computer is restarted the data will be recovered from CU 950 Monitor In the event of a power failure to the monitor e The display goes blank Other units are not affected Printer In the event of a power failure to the printer e Printouts can not be made Other units are not affected 2 9 1 Network interruption Network interruption can occur in two types of network cables e The Ethernet network between the UNICORN computer junction box and the process system e Optional LAN WAN network between the UNICORN computer network printers and servers Ethernet network In the event of interruption of the Ethernet network e Ifthe network is broken between the junction box and the computer the run will continue on the process system controlled by the CU 950 unit located in the junction box Data will be saved in CU 950 The indicators on CU 950 indicate communication error on the displays If the network is broken between the junction box and the process system the run will be interrupted and the system set to PAUSE e In both cases UNICORN indicates DISCONNECTED in System Control LAN WAN In the event of interruption of the LAN WAN network e The UNICORN computer with UniNet connection to the process system continues to run without interruption e Other network equipment
12. 2 Starting the process system 1 Turn onthe UPS 2 Turnonthe main compressed air supply to the system 3 Turnon the purge air and instrument air supplies using the valves on the process cabinet 4 Turn the mains power switch on the junction box to 1 Result The pre purging procedure of the process cabinet starts When successfully finished the yellow PURGE indicator on the junction box is turned on 5 When the purging is completed turn the power switch on the process cabinet to 1 Result Power to the process system is turned on The green POWER indicator on the process cabinet is turned on 6 Turnon the instrument air supply using the valve on the process cabinet 5 3 Starting UNICORN 1 Turn on mains power to the computer and the monitor Log on to Windows ra 2 Start UNICORN by double clicking on the icon on the Windows desktop 2 UNICORN 3 When the Logon dialog appears select a user from the Users list and enter the password If you log on for the very first time select user default and OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 41 Starting OligoProcess EO enter the password default Click OK ML amp 86l a UNICORN logon User name defaut bal Password Cancel Help Refer to the UNICORN user manual Getting Started for a quick guide to UNICORN software It gives a brief introduction to the software structure and the work flow 5 4 Connecting UNICORN to the process s
13. 8 8028 12 Fax 0848 8028 13 UK Tel 0800 616928 Fax 0800 616927 e USA Tel 800 526 3593 Fax 877 295 8102 imagination at work User Manual 28 9578 61 AA
14. D DDD OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 49 B Maintenance A A A A A 50 8 2 Cleaning before maintenance service WARNING When using hazardous chemicals make sure that the entire system has been flushed through thoroughly with acetonitrile and then emptied using inert gas before service and maintenance If a representative from GE Healthcare is to perform maintenance service on the system then the system owner must first clean the system and complete a decontamination report We recommend to always use a decontamination report even if other personnel are performing maintenance or service 8 3 Component maintenance Maintenance and preventive replacement of parts of the major components are described in the manual section in the system documentation The system documentation also includes a spare part list to be used to find common spare parts and their code numbers for ordering WARNING Only use spare parts supplied or approved by GE Healthcare 8 4 Disassembly and assembly The operator must carefully read and understand the instructions supplied for each component before disassembly and assembly of the component Contact your local GE Healthcare representative if further information or help is needed WARNING Always disconnect the mains supply unless stated otherwise before attempting to replace any item on the system during maintenance WARNING Befo
15. EXPLOSION HAZARD Only use non sparking tools for use in potentially explosive atmospheres during operation and maintenance OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 17 Safety instructions 18 gt gt PP PB 2 7 3 Other precautions OligoProcess has a pressurized cabinet which prevents flammable gases from entering However when using OligoProcess the following precautions should always be observed WARNING EXPLOSION HAZARD Always use inert gas when packing the column flushing solvents out of the system and before filling the system with solvents Otherwise air might enter the flow path and create an explosive atmosphere when being mixed with vaporized solvent The user is responsible for preparing procedures for flushing and filling the system flow path using inert gas Contact your local GE Healthcare representative if more information is required WARNING EXPLOSION HAZARD Before starting to use the system make sure there are no unintentional leakages in the system or at connections to the system Make sure there are procedures for checking the system for unintentional leakages during system start up for handling leakages and starting the system after a leakage WARNING EXPLOSION HAZARD Always use self closing quick connectors for connecting to reagent containers and column to avoid leakage WARNING EXPLOSION HAZARD Avoid discharge from static electric
16. GE Healthcare OligoProcess Guide to Safe Operation Contents Introduction LE QIGOPFOCESS SUSTEMM isiin ia 5 1 2 About this Guide to Safe Operation occe ecesssssssssssssscssccssssssssussessesseesse 6 TS THE PLOCESS SYSTEM aianei i a EGE EK 8 PA Control SYSTEM oreinaren enea EE 8 1 5 The oligonucleotide synthesis in OligOProcess wceeesccessssssssesseesseeeee 9 Safety instructions 2l General arsena E A 2e Safety COM PNG CS puins i A EEA 2 3 Material compliance s s s 2 4 Safety labels and other labels 2 5 Intended use of OligoProcess 260 GeneralSGtety PreCAuUtiGiAs cssssssescccssssvesstcercorsssieccccooserearrdargoosssssicccsarsees 2 7 Ex related safety precautions 2 8 Emergency procedures s s 2 9 Power failure and data backup 2 10 Cabinet purging system u s 5 211 Chemicalhresist nc reina E R 2 12 Recycling and disposal inaron a h ERE System overview S SYSTEM AVOUT piadina ia n aaa 23 Sa SUSE TOW DOL siiani ann aA A aR 23 3 3 Flow path components aeseeessecsssssssssssssssesssusssessessesescesssssssuuessseesecesssenssees 24 3 4 Pumps 3 5 Valves 3 6 Conductivity MOMITOF on eecccecsssssssscsssssesssusssessescecseccsssssssuusesssssscessessssies 26 3 7 UV MONITO rinii AENA REN 26 3 8 RreSSUre MONITO eais REAA RERA 27 3 9 Flow monitor 28 SLO ASENSO gernard a a a AA REA EN E AAA 28 SAV COUM titer aena a AA AH R 29 3 12 Pressure control valve oaeeeeee
17. The result of a power failure depends on which unit is affected The UPS uninterruptable power supply supplied with the system is used to avoid loss of data from the control system It allows the system to keep running for at least one standard synthesis cycle during brief power failures in order to avoid unnecessary production stops During this period the system can also be set to a safe wait state in a controlled way for example by running automatic wash and pause procedures Junction box The mains power cables to OligoProcess are routed from the UPS through the junction box If a mains power failure lasts for a longer period than the UPS can handle the power to the entire system will be interrupted However run data can be recovered from the CU 950 unit where run data is stored until the power was interrupted WARNING HIGH PRESSURE Power failure might result in high pressures in the piping system Process system In the event of a power failure to the process system e The run is interrupted in an undefined state e UNICORN indicates DISCONNECTED in System Control e The data collected up to the time of the power failure is available in UNICORN Computer In the event of a power failure to the computer e The UNICORN computer shuts down in an undefined state e The run will continue on the process system controlled by the CU 950 unit located in the junction box Data will be saved in CU 950 The indicators
18. afety labels and other labels on the system and in this guide 2 4 1 Labels in this guide WARNING The text WARNING and or the triangle warning symbol highlights instructions that must be followed to avoid personal injury It is important not to proceed until all stated conditions are met and clearly understood WARNING The triangle EX warning symbol highlights instructions that must be followed to avoid personal injury when working in a potentially explosive environment It is important not to proceed until all stated conditions are met and clearly understood CAUTION The text CAUTION highlights instructions that must be followed to avoid damage to the product or other equipment It is important not to proceed until all stated conditions are met and clearly understood OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Safety instructions IMPORTANT The text IMPORTANT highlights additional instructions that must be followed when operating the system Note The Note sign is used to indicate information that is important for trouble free and optimal use of the system 2 4 2 1D and rating label on the system The identification and rating label Fig 2 1 below is located on the system The label states the general specifications and utilities for OligoProcess The CE and Ex mark on the identification label show that the system fulfills applicable european directives Amersham e
19. can use this manual in the way it is intended e Before you try to operate OligoProcess you must study this entire manual and fully understand the safe use of OligoProcess e You need to have a general understanding of how the computer and Microsoft Windows operating system work In most cases universal computer functions will not be explained e UNICORN must be installed and configured correctly on the computer e You need to understand the basic concepts of automated nucleotide synthesis Terminology and functionalities will be explained only when they differ from normal practice 1 2 4 Associated documentation The documentation package supplied with OligoProcess also includes the following parts e System documentation binders containing detailed specifications descriptions and drawings of the system and components e UNICORN User manuals containing information on using and administrating UNICORN and reference information OligoProcess Guide to Safe Operation 28 9578 61 Edition 7 Introduction 1 3 The process system The process system contains all components required for DNA and RNA oligonucleotide synthesis The following main components are included e Pumps for delivering reagents and solvents e Valves for reagent and solvent selection column selection recirculating flow direction and outlet flow direction e Column e UV cell conductivity cell and flow meter e Pressure sensor and air detection s
20. cccsssssssssssesssssssssssesssssssssssssesssssssssssssssssssssssssssee 29 3 13 Containers for reagents ANd solvents eceecccsscsssssssseeseessesscssssesssees 29 SIA JUNCHO DOK ainiti EEE EEA eins 30 S15 PrOCESSCODINET aeieea Ea AN ts 31 3 16 SAPELY SYSTEM iinei ii A AEE 34 S17 Electrical CONMECHONS reseusenieanan anun 35 Installation 4 1 Environmental requirements oacccecsssssssssssesessscssccssssssssusseesseseesssssssssassees 37 4 2 SIE rEG IENMNENIS iiien e REER EEE 37 AS gt PUTA CSKIG ean NR a an 38 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA iii Contents 44 PHYSICAL TASTCINATION eesccsssssiccscccssievsnvscssssssccccsscoissnvssissssesuassecssosssovvsvesssesseee 4 5 Flushing and filling the system flow path 5 Starting OligoProcess Sel Gen rliiewcaenccheanteaniy 5 2 Starting the process system 5 3 Starting UNICORN asierea ean ea ENERE 5 4 Connecting UNICORN to the process system wees 42 6 Synthesis preparation 6 1 Preparation Of SOLUTIONS wceeccecccssssssessssssccssssssssnsssssssssssssssssuseeeseeee 43 6 2 FPA CKING EFS ColuM esessiscasssessessaivitionvercastossssosebsssuanwevisebvbetesshiesdeesnneoonoes 45 6 37 Connecting ENS COMA siassssssessscsssnsSaavssteseesssssssordanvesstovvoscscsbosseanevesieadyoos 45 7 Operation 7 1 General wee 7 2 Creatinga method 7 3 Final preparation ALE Starting ATUN ree Ren tien ibs naa L E N 7 5 Buting a rim ee eee aa E Ee A AEE T EEE 7 6 Viewing and pri
21. chedule 8 1 General Regular maintenance is important for safe and trouble free operation of OligoProcess The user should perform daily and monthly maintenance Preventive maintenance should be performed on a yearly basis by qualified service personnel For maintenance on specific instruments read the manual carefully and follow the instructions WARNNG To avoid risk of injury maintenance or service should only be performed by properly trained personnel and in accordance with the instructions WARNING Do not perform any type of maintenance work while the system is powered electrically or pneumatically or when the piping system is pressurized Note that the piping system can be pressurized even when the system is closed down WARNING EXPLOSION HAZARD Always use inert gas for flushing solvents out of the system and before filling it with solvents Otherwise air might enter the flow path and create an explosive atmosphere when getting mixed with solvents WARNING EXPLOSION HAZARD Avoid discharge from static electricity when working in potentially explosive atmospheres Always use suitable clothing WARNING EXPLOSION HAZARD Only tools and equipment for use in potentially explosive atmospheres should be used for operation and maintenance WARNING EXPLOSION HAZARD Before starting to use the system make sure there are no unintentional leakages in the system or connections to it gt D
22. ensor e Pressure control valve for controlling the backpressure in the flow path 1 4 Control system 1 4 1 UNICORN control software UNICORN is a complete package for control and supervision of OligoProcess from the computer and monitor supplied It consists of software for interfacing the controlling computer to the process system The software runs under Microsoft Windows operating system UNICORN is supplied with a number of ready made method templates which provide easy creation of methods for syntheses For more information about UNICORN control system see the UNICORN user manuals supplied 1 4 2 Operator terminal OligoProcess also includes an Ex classified operator terminal which can be placed close to the process system The terminal is connected to the controlling computer which allows the operator to control and monitor the process from within the process room OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Introduction 1 5 The oligonucleotide synthesis in OligoProcess This section gives a brief overview of the process steps in a typical oligonucleotide synthesis using OligoProcess The synthesis cycle which adds one residue to the growing oligonucleotide on the solid support consists of four major steps 1 Detritylation which involves removal of the 5 DMTr group from the terminal residue on the solid support to make the hydroxy group available for coupling 2 Coupling which involves act
23. explosive atmospheres Always use suitable clothing WARNING EXPLOSION HAZARD Only use non sparking tools for use in potentially explosive atmospheres during operation and maintenance WARNING HEAVY OBJECT Take care when moving the system 4 4 1 Mains supply WARNING Make sure that the power supply marked on the system label corresponds to the main voltage intended for the system The process system is labelled with the mains supply voltage and frequency This information can also be found in this Guide to Safe Operation WARNING EXPLOSION HAZARD Avoid discharge from static electricity in potentially explosive atmospheres Make sure that the entire system including the column is properly connected to the plant grounding network gt gt oppe 4 4 2 Communication e Connect the network signal cables computer and CU 950 according to the electrical drawings in the system documentation e Make sure that UNICORN control software is installed on the computer 4 4 3 Compressed air inert gas e Connect the compressed air to the process system according to the system documentation e Set the pressure regulator for the compressed air to 6 bar OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 39 Installation 40 4 4 4 Inlet and outlet pipes Note To prevent bacterial growth the system flow path is filled with 20 ethanol at delivery e Connect the pipes and tube
24. guide 1 1 OligoProcess system OligoProcess is a custom designed system for reliable and cost effective production of DNA and RNA oligonucleotides The system uses flow through column technology to keep the amidite consumption to a minimum Fig 1 1 OligoProcess system OligoProcess consists of a process system junction box computer with monitor and UNICORN control software and a separate operator terminal OligoProcess features e Production range from 50 to 500 mmol 100 to 1000 mmol or more of therapeutic oligonucleotides e Explosion proof design and industrial grade components that withstand harsh synthesis chemicals e System control by UNICORN allows for fast and easy start of the production process and simple method scale up OligoProcess Guide to Safe Operation 28 9578 61 Edition A 5 Introduction s 1 2 About this Guide to Safe Operation This guide is intended to highlight certain conditions that must be followed to obtain and maintain safe operation of OligoProcess system OligoProcess is an Ex classified system wherefore this guide also contains special safety information related to working in a potentially explosive environment Make sure that the information in this guide together with the system documentation supplied is fully understood before the system is used 1 2 1 Contents The table below describes the content in each chapter in this manual C
25. hapter Contents 1 Introduction Brief overview of OligoProcess and information about this manual 2 Safety instructions Instructions that must be followed for safe use of OligoProcess labels and emergency procedures 3 System description Overview of the system components brief description of the system flow path and major components 4 Installation Basic instructions for installing the system 5 System start up Instructions for starting the system and connecting the system to UNICORN 6 System preparation Instructions for preparing the system ora run 7 Operation nstructions for creating a method for a synthesis final checks for starting a run and viewing and printing the result 8 Maintenance aintenance schedule and recommendations for preventive maintenance and replacing spare parts 9 Troubleshooting Overview of error symptoms possible causes and actions 10 Reference information System overview wetted parts a 6 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Introduction 1 2 2 Typographical conventions Menu commands the names of dialog boxes and windows the contents in dialog boxes and windows and option buttons are written in a bold typeface Menu commands are written with the menu name and the command separated by acolon For example File Open refers to the Open command in the File menu 1 2 3 Prerequisites The following prerequisites must be fulfilled before you
26. igoProcess Guide to Safe Operation 28 9578 61 Edition AA 31 System overview monitor enclosing Finally the air exits through a purge control unit on the UV monitor enclosing Fig 3 12 Purge control unit Purging modes The purging system operates in two modes e Purging mode is automatically started when the mains switch on the junction box and the purge air supply are turned on During this procedure several predetermined cabinet volumes of air under pressure are flushed through the cabinet to remove any flammable gases remaining in the cabinet Then the system automatically goes to Pressurization mode and the PURGE indicator on the junction box is turned on It is now possible to turn on the power supply to the process system with the POWER switch on the process cabinet e Pressurization mode is used during normal operation to maintain a certain overpressure in the cabinet to prevent flammable gases from entering as long as the system power is turned on If the purging system fails maintaining the specified overpressure in the cabinet the power supply to the process system is automatically turned off 32 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview Purge control unit The purge control unit on the UV monitor enclosing contains equipment for measuring the flow and pressure of the outlet air The unit also controls a proportional valve located at the c
27. is not exceeded by any of the pumps The pressure switches are hard wired meaning that the shut off function of the pumps is independent of the software Fig 3 2 Pump and pressure switch OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview 3 5 Valves The flow path in OligoProcess is controlled by two different types of diaphragm valves One is a 2 way valve used for turning the solvent supply on and off The other type is an advanced multiway multiport valve which can direct the flow in different directions The valves have different sizes depending on the number of ports on the valve The inlet and outlet ports have two different dimensions depending on the flow rate where they are used in the system Each valve is equipped with isolated proximity sensors The diaphragm valves are actuated by compressed air which is distributed by miniature pneumatic control valves Fig 3 3 Diaphragm valves and pneumatic control valve OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 25 System overview 26 3 6 Conductivity monitor The conductivity monitor provides accurate on line monitoring of conductivity The accurate response of the monitor coupled with high precision over a wide measuring range makes it ideal for any oligosynthesis application The conductivity monitor consists of a sensor and a transmitter The sensor has four electrodes and integral Tri Clamp fittings It is equipped with
28. ity in potentially explosive atmospheres Make sure that the entire system including the frame piping and column are connected to the plant grounding network OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Safety instructions 2 8 Emergency procedures This section describes the emergency stop of OligoProcess 2 8 1 Emergency stop When there is a risk of injury e Press the EMERGENCY STOP button on the process cabinet Fig 2 2 Emergency stop button on the process cabinet Result e The pumps stop The high voltage to the pumps is shut off e The valves switch to the default positions see system documentation e The method run is set to PAUSE WARNING HIGH PRESSURE Emergency shutdown might result in high pressures in the piping system 2 8 2 Emergency stop reset Note Check the system for faults before resetting it To reset the emergency stop e Turn and pull out the EMERGENCY STOP button Result e High voltage to the system is resumed Pressing CONTINUE will resume the method run execution OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 19 Safety instructions 20 2 8 3 Connecting alarm indicators An alarm indicator for example a lamp or siren can be connected to the junction box This indicator is activated by an alarm in UNICORN which can be issued at a number of occasions listed in the system documentation 2 9 Power failure and data backup
29. ivation of the incoming amidite with activator and formation of the 3 5 phosphite link to the growing oligonucleotide Note Completely anhydrous conditions are essential for the efficiency of this step 3 Oxidation of the phosphite triester to a phosphotriester using iodine Phosphorothioate linkages can be introduced at this stage by using thiolation reagent instead of an oxidising agent 4 Capping of unreacted 5 hydroxyl groups to form acetates to prevent the formation of heterogeneous oligonucleotide products Before the actual process the inlet tubing is purged with the correct reagents and solvents During the process several washing steps are included between the reaction steps above These steps ensure that no residual reagent from the previous step will interfere with the next reaction step OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 9 Introduction 10 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Safety instructions 2 Safety instructions This chapter describes safety compliance safety labels general and EX related safety precautions emergency procedures power failure and recycling of OligoProcess 2 1 General IMPORTANT All users must read this entire Guide to Safe Operation to fully understand the safe use of OligoProcess OligoProcess is designed and manufactured in order to provide a high level of personal safety However the level of risk is highly dependent on the
30. le 8 1 lists the maintenance operations that should be performed by the user at regular intervals Interval Action Instructions reference Daily System Leak inspection Visually inspect the system for leaks Wash the system flow path 1 Wash the flow path with acetonitrile between runs 2 Ifleaving the system for a few days the flow path should be left filled with acetonitrile Every 6 months Valves Check membranes on the most frequently used valves See separate valve manual Monitors Check the monitors Calibrate the monitors Adjust if necessary Every year or when required System Clean the system Remove chemical stain and dust Spray the system with 20 ethanol and wipe off Pumps Replace gaskets See separate pump manual Valves Replace membranes See separate valve manual Piping system Replace gaskets and O rings Table 8 1 User maintenance schedule 52 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Troubleshooting ex 9 Troubleshooting This chapter provides corrective actions to known problems that might occur when running a synthesis 9 1 General Problems that are not covered in this chapter and those that can not be solved using your own experience should be carefully documented and forwarded to the local GE Healthcare representative 9 2 Chemical problems Common causes of chemical problems are Water gt 30ppm in reagents Use q
31. ligoProcess is made of stainless steel type 316L The outer dimension of the pipes are 1 2 3 4 and 1 depending on location The pipes are connected with Tri Clamp safety clamps TC25 and TC50 For a detailed description see the system documentation OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 23 System overview 24 3 2 2 Inlet pipes Reagents solvents and cleaning solutions are introduced into the system through pipes 22 pcs connected to the inlet valves 3 2 3 Outlet pipes The outlet pipes 4 pcs are connected to the outlet valves 3 3 Flow path components All components in the system flow path such as pumps valves sensors and flow cells are classified according to the prevailing EX standards The main components are briefly described in the following sections For more information on a specific component see the documenation for the component and the piping diagram included in the system documentation 3 4 Pumps There are seven pumps used for liquid delivery in the system P 201 207 The pumps operate in different flow rate intervals in the range 0 2 20 ml min depending on where they are used in the system Each pump has a fan cooled motor for low voltage supply which is enclosed in a flameproof enclosure The motors are powered by frequency converters located in the process cabinet Pressure switches PS 251 257 connected after each pump ensure that the maximum system pressure limit
32. most current information 10 5 Ordering information For ordering information see the system documentation OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 55 Reference information 56 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA www aktaoligopilot com www primersupport com GE Healthcare Amersham Biosciences AB Bj rkgatan 30 751 84 Uppsala Sweden OligoProcess and UNICORN are trademarks of GE Healthcare Ltd GE tagline and GE monogram are trademarks of General Electric Company M icrosoft and Windows are either trademarks or registered trademarks of Microsoft Corporation in the United States and or other countries All goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them GE Healthcare reserves the right subject to any regulatory and contractual approval if required to make changes in specifications and features shown herein or discontinue the product described at any time without notice or obligation Contact your local GE Healthcare representative for the most current information 2005 General Electric Company All rights reserved Amersham Biosciences AB a General Electric company going to market as GE Healthcare GE Healthcare Amersham Biosciences AB Bjorkgatan 30 751 84 Uppsala Sweden GE Healthcare Amersham Biosciences Europe GmbH Munzinger Strasse 9 D 79111 Freiburg Germany GE Healthcare Amersham
33. nnection points gt PP gt D OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 45 6 Synthesis preparation 46 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Operation 7 Operation This chapter briefly describes how to start a run and after run procedures 7 1 General IMPORTANT To avoid risk of injury operation and user maintenance should be performed by properly trained personnel only and in accordance with the instructions WARNING EXPLOSION HAZARD The operator must not use tools cellular phones hand tools etc or equipment that are not suitable for potentially explosive environments 7 2 Creating a method See the UNICORN user manuals for instructions on how to create a method 7 3 Final preparation Before starting any method we recommend that a certain number of checks are performed to make sure that problems are not encountered once the run has been started WARNING EXPLOSION HAZARD Before starting to use the system make sure there are no unintentional leakages in the system or connections to it e Check that the column is properly connected between valve XV 051 and XV 052 e Check that the inlet pipes are connected to the correct reagent and solvent supplies e Check that sufficient quantities of reagents and solvents for the run are available e Check that the waste container is not full and will accept the volume diverted to it
34. ns to be followed when using OligoProcess 2 6 1 Warnings The Warning symbol highlights instructions that must be strictly followed to avoid personal injury Do not proceed until the instructions are clearly understood and all stated conditions are met WARNING OligoProcess should be installed and prepared by GE Healthcare personnel WARNING Only use qualified personnel with a thorough knowledge of the system and processes to perform start up operation and maintenance of the system WARNING The system must not be opened by the user It contains electrical circuits which can give a lethal electric shock WARNING Make sure that the power supply marked on the system corresponds to the main voltage intended for the system WARNING The system must always be correctly grounded to earth at the mains outlet WARNING Always disconnect the mains supply unless stated otherwise before attempting to replace any item on the system during maintenance Deep OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 15 Safety instructions WARNING HIGH PRESSURE The emergency shutdown might result in high pressures in the system flow path WARNING HAZARDOUS CHEMICALS When using hazardous chemicals always wear protective glasses and clothing for example acetonitrile resistant gloves WARNING SPRAYING LIQUID Always wear protective clothing and glasses to prevent injurie
35. nting the result ss ssssssissssssrsssrssrssrissrsssssssrssrsrrensssse 48 Li GATEMGUTU GIG Storage maere i a ER 48 8 Maintenance Bile General ierse EEE E ENA 49 8 2 Cleaning before maintenance service n s 50 8 3 Component MAINTENANCE oaaeeeeseeescsssssessesssecsesssesecssseescessssccessssccesssecessnees 50 8 4 Disassembly ANd assembly sesssssssssssssscsssssssssssseessesscssccssssssssseseseesees 50 8 5 Replacement Of FUSCS areenan E Aa 51 8 6 Monitor calibration 8 7 User maintenance schedule oaaaaessscesssssssssssssssssssssssssssessssenceeneecceeeeeeeeee 52 9 Troubleshooting FT GENETTA ueia Ta E E R E 53 9 2 CHEMICAL problems mrsiti aE EA 53 93 UV cur problems cascteecsscecccosscssesssentbecssssssccccbasseonevatesusecsssctosssosereesieeued 53 94 COnNAUC VITY UV Essin i e E 54 9 5 Pressure curve 9 6 Purge system 10 Reference information 10 1 OlGOPLOCESS SUSTEMM sssssiccccsesscesccccsessssseecieciaasesssccscobveststccotaivecsscotovtate 55 10 2 SPECIHICALONS i nissenana a ARARE 55 10 3 Wetted materials sieniin a 55 10 4 System FECOMMENCATIONS cs scccccessssisssssssccscensesvsvsassiasssesccsssevnececvtsiastass 55 10 5 Ordering infomation sisssssssscdsssecdveeustainassdssiecseeaevaesaaaadssisscsstoreccttvaadiatass 55 _ S iv OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Introduction 1 Introduction This chapter contains a brief introduction to OligoProcess system and a description of this
36. ocess cabinet Uninterruptible power supply Junction box Three o phase mains Computer ii s Fig 3 13 Mains cables The cable from the three phase mains power supply is routed through the UPS to the junction box The process cabinet and the computer are connected with separate cables WARNING HIGH VOLTAGE The mains cable to the process system should only be connected by authorized service personnel Faulty connection might result in live system parts that can give a lethal electric shock OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 35 System overview 36 3 17 2 Communication cables Hazardous area Safe area Process cabinet Junction box External signal cables optional I O cables Network cable Network Switch I O cables Operator terminal Fig 3 14 Communication cables An Ethernet cable is connected between the computer and the junction box The CU 950 unit inside the junction box is the interface between the Ethernet network and the signal network in the process system The signal network continues to the process cabinet through a separate optical cable Other signal cables are bundled in an Ex protected cable The operator terminal inside the process room is connected to the controlling computer through an Ex protected cable and a switch The switch makes it possible to connect the operator terminal to other optional c
37. ompressed air inlet on the process cabinet This makes it is possible to flush a programmed amount of air during purging mode and to adjust the pressure to a programmed value during pressurization mode The purge control unit has an operator panel for programming the desired values 3 15 2 Switches push buttons and status indicators The cabinet has switches push buttons and status indicators as described in Table 3 2 Indicator Switch Color Description Push button POWER Turns on off power to the process system mains switch Enabled only if the cabinet is purged RUN Enables the purge system Should always switch be turned on 1 BYPASS Bypasses the purge system Makes it switch with key possible to run the system even if the cabinet is not purged or pressurized Should normally be turned off 0 WARNING For service use only The key should be kept separated from the system during normal operation POWER Green The light is turned on when the POWER indicator switch is turned on AND the purging procedure of the process cabinet has successfully finished PAUSE Red Pressing the button in RUN mode push button e sets the method run to PAUSE e stops the pumps e sets the valves to default positions CONTINUE Black Pressing the button in PAUSE mode push button e sets the method run to RUN e starts the pumps with the set flow rate e resumes valve status ft OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 33 Sys
38. omputers used for controlling the process system OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Installation 4 Installation This chapter informs about procedures and precautions that are particularly important when installing and testing the system in order to maintain the system compliance with the prevailing EX standard Any equipment connected to OligoProcess must also meet the requirements of the ATEX 94 9 EC or other equivalent international safety standard A detailed description of the installation procedure is found in the nstallation Guide supplied with the system 4 1 Environmental requirements In order to minimize any safety risks and to obtain optimal function from OligoProcess it is important to pay close attention to the environment in which the system is used These conditions include e minimal dust e placement on a level floor e avoiding corrosive gas e avoiding direct sunlight e avoiding strong magnetic fields e avoiding vibration 4 2 Site requirements Make sure that the following site requirement are fulfilled Electrical power L1 L2 L3 N PE 3 x 400 V 50 Hz Compressed air pressure Min 5 bar g Max 10 bar g Compressed air flow rate Min 350 l min during normal operation Min 500 l min during purging Media feed requirements Inlet lt 6 bar Outlet gt atmospheric pressure lt 0 6 bar g Room temperature 18 30 C OligoProcess Guide to Safe O
39. peration 28 9578 61 Edition AA 37 Installation 4 3 Unpacking IMPORTANT Unpacking and installation of OligoProcess must be performed by personnel authorized by GE Healthcare WARNING Never remove bolts brackets that are not marked when equipment is still in the crate Unpack the system as follows 1 Remove the front side and back panels by loosening the bolts brackets marked with black paint 2 Loosen the bolts brackets holding the equipment to the crate bottom 3 Lift the equipment out of the crate using a pallet lifter suitable for the weight and size of the equipment 4 Check that all equipment is enclosed in the crate according to the packing list If not immediatley inform your local GE Healthcare representative 4 3 1 Visual inspection Visually inspect the OligoProcess system to see that there has been no physical damage to the system during handling and transportation Document any damages and contact your local GE Healthcare representative 38 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Installation 4 4 Physical installation Install the system as described in the Installation Guide supplied See also the Ex related precautions described in this section IMPORTANT Unpacking and installation of OligoProcess must be performed by personnel authorized by GE Healthcare WARNING EXPLOSION HAZARD Avoid discharge from static electricity when working in potentially
40. rate conductivity monitor manual 9 5 Pressure curve Error symptom Possible cause Corrective action Erratic flow noisy baseline signal irregular pressure trace Gas bubbles passing through or trapped in the pump Check that there is sufficient supply of liquid Check all connections for leaks Blockage or partial blockage of flow path Flush through to clear blockage If necessary replace tubing 9 6 Purge system Error symptoms Possible causes Action The specified pressure in the cabinet cannot be maintained The cabinet door is not closed Close the door The UV monitor enclosing is not air tight Check the UV monitor enclosing The compressed air supply is not sufficient Check the air supply to the system 54 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Reference information 10 Reference information 10 1 OligoProcess system OligoProcess is a custom designed system for reliable and cost effective production of DNA and RNA oligonucleotides Fig 10 1 OligoProcess system 10 2 Specifications For system performance and technical specifications see the system documentation 10 3 Wetted materials For information on wetted materials see the system documentation 10 4 System recommendations Refer to the UNICORN user manuals supplied or contact your local GE Healthcare representative for the
41. re disassembly check that there is no pressure in the piping system WARNING After assembly the piping system must be tested for leakage at maximum pressure for continued protection against injury risks due to fluid jets burst pipes or explosive atmosphere OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Maintenance 8 8 5 Replacement of fuses ass A WARNING Turn off the system mains switch before replacing fuses If a fuse repeatedly blows switch off the system mains switch and contact your local GE Healthcare representative WARNING For continued protection from fire hazard replace only with same type and rating of fuse 8 6 Monitor calibration For reliable performance the monitors should be calibrated at regular intervals All monitors should be checked at least 2 times per year Refer to the instrument manual for calibration of the instrument Note that calibration is only a comparison of the instrument to a known reference If adjustments are necessary we recommend that you contact the manufacturer of the instrument or GE Healthcare for help CAUTION The guarantee expires immediately if the instrument is adjusted by someone other than from GE Healthcare the instrument manufacturer or personnel authorized by GE Healthcare OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 51 8 Maintenance lC 8 7 User maintenance schedule Tab
42. rview 3 9 Flow monitor There are four flow monitors FIT 141 144 in the system in order to make sure that the flow rate during the synthesis is correct Three of them are placed at the reagent and solvent inlets and one after the column The monitor is a mass flow measuring system which consists of a sensor and a transmitter which are installed separately The transmitter is the power and communication interface to the process cabinet The monitor also measures the temperature and density of the process liquid 28 Fig 3 7 Flow sensors and transmitters 3 10 Air sensor The air sensor AE 151 is placed before the column in the flow path in order to prevent gas from entering the column If gas is detected during a run UNICORN issues an alarm which makes it possible to for example bypass the column or stop the run Fig 3 8 Air sensor OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview 3 11 Column Make sure that the column used fulfills the pressure and flow rate specifications stated in the system documentation WARNING All users must read the instructions supplied with column especially the safety instructions to fully understand the safe use of the column WARNING EXPLOSION HAZARD Avoid discharge from static electricity in potentially explosive atmospheres Make sure that the system including the column is connected to the plant grounding network gt gt 3 12
43. s caused by fluid jets if leakage should occur WARNING Only use spare parts supplied or approved by GE Healthcare WARNING OVER PRESSURE e Make sure that the column withstands the expected operating pressures e Never block the outlet hoses because this will create over pressure and might result in injury WARNING All cabinet doors and instrument covers must be properly closed during operation WARNING HEAVY OBJECT Take care when moving the system gt gt PEP gt P 2 6 2 Cautions The Caution sign highlights instructions that must be followed to avoid damage to the product or other equipment Be sure not to proceed until the instructions are clearly understood and all stated conditions are met CAUTION Always make sure that the column media columns and system components are compatible with reagents and solvents at the concentration time and temperatures used CAUTION Make sure that the liquid flow path is filled with acetonitrile when the system is not used 16 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Safety instructions 2 7 EX related safety precautions This section contains instructions for working in potentially explosive areas which must be followed in order to maintain the EX classification of OligoProcess The information is suggested best working practice but shall not take precedence over individual responsibilities or local regula
44. s come into contact with skin wash immediately and generously with water If reagents or solvents come into contact with the eyes wash thoroughly with water and consult a physician as soon as possible If any reagents or solvents are ingested consult a physician immediately gt PP gt OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 43 6 Synthesis preparation E 6 1 1 Tips for reliable production Some tips for preparing the reagents to ensure reliable production e Oligonucleotide synthesis requires completely anhydrous conditions since traces of water in the reagents and solvents will significantly decrease the synthesis efficiency e Work quickly with preparing connecting and disconnecting containers to avoid allowing any moisture into the reagents and solvents e Acommon source of moisture in oligonucleotide synthesis is poor quality inert gas Make sure that the inert gas supply is dry and free from carbon dioxide e Always follow the manufacturer s recommendations for reagent preparation and use 6 1 2 Recommended procedure for filling a container WARNING EXPLOSION HAZARD When preparing reagents in an empty containers always first fill the container with inert gas Work quickly with open containers Otherwise oxygen and organic solvents might mix and create a potentially explosive atmosphere Filling an empty container Note Work quickly to avoid moisture and oxygen to enter the
45. s for reagents solvents and product collection to the correct inlet and outlet connections on the process system see the system documentation for piping drawings e Make sure that the inlet and outlet pipe dimensions meet the specification see the system documentation 4 5 Flushing and filling the system flow path To prevent bacterial growth the system flow path is filled with 20 ethanol at delivery The ethanol should be flushed out before filling the system for performing the function test WARNING EXPLOSION HAZARD Always use inert gas for flushing solvents out of the system and before filling it with solvents Otherwise air might enter the flow path and create an explosive atmosphere when being mixed with vaporized solvents The user is responsible for preparing procedures for flushing and filling the system flow path using inert gas Contact your local GE Healthcare representative if more information is required OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Starting OligoProcess 5 Starting OligoProcess This chapter provides instructions for the initial start up of OligoProcess in order to prepare for the testing before the system is used in production 5 1 General IMPORTANT OligoProcess should be installed and prepared by personnel authorized by GE Healthcare It is assumed that the system has been installed in accordance with the instructions in chapter 4 Installation 5
46. sphere is not expected to occur with normal handling and any eventual occurrences are only occasional and temporary OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 11 Safety instructions 12 gt gt Equipment group and category Oligoprocess belongs to equipment group II and equipment category 3 It is designed to be capable of ensuring a normal protection level It is intended for use in areas in which explosive atmospheres caused by gases vapors or mists are unlikely to occur or if they do occur are likely to do so only unfrequently and for a short period only The EX category of the equipment must also be in conformity with the protection level of the room where it is used Temperature class and explosion group The material in OligoProcess belongs to temperature class T4 and explosion group IIB The EX classification is stated on a label on the system See section 2 4 2 ID and rating label on the system 2 3 Material compliance Materials that come in contact with solvents in OligoProcess are selected among those recognized as safe for use in food and drug handling equipment as described in GMP and for their chemical compatibility In the system documentation you will find information about the design and materials used in the system All wetted parts are specified Make sure that the system also in this perspective is suitable for your needs and application s 2 4 Safety labels and other labels There are s
47. tem overview Indicator Switch Color Description Push button EMERGENCY STOP Red Pressing the button push button e stops the pumps by shutting off the high voltage to the pumps e sets the valves to default positions e sets the method run to PAUSE Alarm buzzer Indicates an alarm in UNICORN Table 3 2 Indicators switches keys and push buttons on the process cabinet 3 15 3 Gauges and valves The cabinet is equipped with gauges and valves as described in Table 3 3 Gauge Valve Description Flow indicator Shows the flow rate of the purge air Manometer Shows the cabinet pressure Purge air valve On off valve for the purge air supply Must be turned on to allow purging Instrument air valve On off valve for the instrument air supply Table 3 3 Gauges and valves on the process cabinet 3 16 Safety system OligoProcess is equipped with a safety relay in the junction box which external alarm indicators at the plant e g a lamp or siren can be connected to When for example UNICORN raises an alarm signal the relay signal can be used to activate the external alarm indicator Refer to drawings in the system documentation for how to connect these signals to the safety relay in the junction box 34 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA System overview Ess 3 17 Electrical connections 3 17 1 Mains cables Hazardous area Safe area Pr
48. tions 2 7 1 Risk assessment WARNING Perform a risk assessment for any risks due to the process or process environment Evaluate the effect the system and the processes where it is used has to the classification of the hazardous area The process might cause the area to increase or the zone classification to change Implement the risk reduction measures needed including use of personal protection equipment To be considered when performing the risk assessment e All personnel involved in operating maintaining and servicing the system must have proper knowledge of ATEX and ATEX systems e Risk of liquid leakage in case of failure or breakage of the system Prepare procedures for handling leakages and testing after corrective actions e Risk of air entering the flow path during filling and emptying the system which might create an explosive atmosphere when being mixed with vaporized solvent Always use inert gas e Risk of liquid leakage when connecting or disconnecting to the reagent containers or the column Always use self closing quick connectors e Risk of smaller leakages during maintenance resulting in a classification of the area as zone 1 Make sure there are no active ignition sources in the area during maintenance 2 7 2 Personal precautions WARNING EXPLOSION HAZARD Avoid discharge from static electricity when working in potentially explosive atmospheres Always use suitable clothing WARNING
49. uality reagents and molecular sieves when needed Old reagents Not enough of or no purge of amidites and or solvents prior to the synthesis 9 3 UV curve problems Error symptom Possible cause Corrective action Ghost peaks Dirt or residues in the flow path Clean the system from previous runs Residues in the column from Clean the column according to previous runs the column instructions Noisy UV signal signal drift or Bad UV fiber connections Check the connections of the UV instability cell optical fiber Replace if necessary Dirty UV cell Clean the UV cell using methanol OligoProcess Guide to Safe Operation 28 9578 61 Edition AA 53 9 Troubleshooting 9 4 Conductivity curve Error symptom Possible cause Corrective action Baseline drift or noisy signal Leaking tube connections Tighten the clamps If necessary replace the clamps Bad pump See separate pump manual Dirty conductivity cell Clean the conductivity cell using methanol Absolute conductivity value is wrong Bad calibration Calibrate the conductivity cell see separate conductivity monitor manual Calibration solution not correctly prepared Recalibrate using a new calibration solution Incorrect or unstable reading Bad pump or valve function Check the pump and the valves The temperature compensation not properly set Check the temperature compensation see sepa
50. ystem 1 In System Control select System Connect System Help Settings Ctr s Calibrate E Take Cont Report Maintenar 2 Select the appropriate system name and click OK Result When UNICORN is connected to the process system the green RUN indicator in the status bar in UNICORN is lit 1 R Run Hold Pause Continue End SSS 42 OligoProcess Guide to Safe Operation 28 9578 61 Edition AA Synthesis preparation 6 6 Synthesis preparation This chapter describes how to prepare the system for oligonucleotide production 6 1 Preparation of solutions This section describes the preparation of reagents and solvents for use with OligoProcess WARNING EXPLOSION HAZARD Always use inert gas when packing the column flushing solvents out of the system and before filling the system with solvents Otherwise air might enter the flow path and create an explosive atmosphere when being mixed with vaporized solvent WARNING EXPLOSION HAZARD Avoid discharge from static electricity in potentially explosive atmospheres Make sure that the system including the column are connected to the plant grounding network WARNING HAZARDOUS CHEMICALS When using hazardous chemicals all suitable protective measures such as wearing protective glasses and acetonitrile resistant gloves must be taken WARNING HAZARDOUS CHEMICALS Work in a properly ventilated room Do not inhale fumes from the solutions If reagents or solvent
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