GE Healthcare Instructions 18-1174-61 AC FlexStand Cartridge Holder Scope This user guide describes how to assemble and use the standard FlexStand™ (FS-01S and FS-01S-30) and the low-void-volume FlexStand (FS-03LVS and FS-03LVS-30) cartridge holders. Topics include: • Product descriptions • Assembly instructions • Maintenance procedures. Audience This user guide addresses the needs of scientists, process engineers, and technicians who operate laboratory-scale cross-flow systems. The level of information presented in this guide assumes the user possesses basic laboratory and technical skills, and has the knowledge and documentation to safely operate any usersupplied equipment connected to the FlexStand cartridge holder. If you need assistance with the instructions in this guide, contact GE Healthcare for more information. Table of contents 1. Safety.......................................................................................................................................................................2 2. FlexStand cartridge holder ............................................................................................................................6 3. Setting up the cartridge holder ................................................................................................................ 10 4. Operation ............................................................................................................................................................ 15 5. Troubleshooting ............................................................................................................................................... 16 6. Maintenance...................................................................................................................................................... 16 7. Specifications.................................................................................................................................................... 17 8. Further information........................................................................................................................................ 18 9. Spare parts and accessories ..................................................................................................................... 19 1 Safety Safety instructions Everyone who works with the FlexStand cartridge holder should read, understand, and follow the instructions in this user guide and the safety guide, Cross-Flow System Safety Instructions. If any operator does not understand an instruction, they should stop working with the FlexStand cartridge holder and contact GE Healthcare for guidance. You should save the user guides and safety guide and make them available to all users of the FlexStand cartridge holder. Intended use GE Healthcare designed the FlexStand cartridge holder for laboratory-scale filtration of biological solutions using hollow fiber membrane cartridges under the conditions stated in this user guide and the GE Healthcare cartridge operating guide. If you use the system and cartridges in a manner not specified by GE Healthcare, you may impair the protection provided by the system and cartridges. When using any laboratory, pilot-scale, or production cross-flow equipment, the potential exists for personal injury unless you follow established safety procedures. When using GE Healthcare products, you should follow OSHA, federal, state, and local safety regulations for equipment installation and operation. You should follow your company’s safety regulations and good engineering practices. You should follow the specific safety instructions provided in this user guide and any original equipment manufacturer user guides provided with your system. Only qualified personnel who are adequately trained and who understand the operating instructions should install, operate, maintain, and inspect the FlexStand cartridge holder. Operators should run water through a new system until they are familiar with its operation and are confident the system is running properly. 2 Instructions 18-1174-61 AC Warnings, cautions and expert advice This user guide uses symbols and blocks of text to provide you with safety warnings and other important information. WARNING! A safety warning flag describes conditions or actions that can cause bodily harm and describes how to avoid the risk. CAUTION! A caution flag describes conditions or actions that can damage equipment and describes how to avoid the risk. Tip: An expert advice flag provides you with information that can help you use your equipment efficiently or achieve the best results. Safety warnings WARNING! If you overpressurize a membrane system with compressed air during integrity testing, system components can rupture causing bodily harm. • To avoid the rupture of a system component due to over pressurization with compressed air, use a pressure regulator to limit the pressure of your compressed air supply to the maximum operating pressure of your system. • Wear the appropriate personal protection devices when testing the system. Instructions 18-1174-61 AC 3 WARNING! If the system leaks, it can release potentially hazardous process fluids or cleaning fluids causing bodily harm. • To prevent leaks and the release of potentially hazardous process or cleaning fluids, limit feed pressure to the maximum operating pressure of your system, periodically check parts for wear, and ensure you assemble the components correctly. • To monitor system pressure, GE Healthcare recommends that you install pressure gauges on the system as described in this user guide. • Periodically inspect the system’s gaskets, seals, and connections for wear. Ensure you assemble the system correctly following the instructions in the system guide. • Wear the appropriate personal protection devices and clothing when operating and cleaning the system. Basic personal protection devices include protective clothing, safety glasses, and hearing protection. • Use additional protective devices (fume hood, respirator, etc) if the nature of your product or your company’s safety regulations require it. WARNING! Mishandling potentially hazardous process and cleaning/storage solutions can cause bodily harm through exposure to skin, eyes, and respiratory system. • To safely handle potentially hazardous process and cleaning/storage solutions, read the MSDS for the solutions you use. Follow the handling and safety instructions on the MSDSs and use the personal protection equipment required by your company, local, state, and federal laws. WARNING! Inspecting the system without disconnecting the power cable, disconnecting the compressed air supply, and decompressing the system, can result in bodily injury from the accidental starting of the pump or unexpected release of pressure. • To prevent bodily injury, disconnect the power cable, disconnect the compressed air line, and depressurize the system before performing inspections and disassembling the system. 4 Instructions 18-1174-61 AC WARNING! Failure to use tubing clamps to secure tubing on tubing nipples and hose barb fittings can cause unexpected leaks of potentially hazardous fluids and result in bodily harm. • To prevent unexpected leaks and possible bodily harm, use tubing clamps on all tubing nipple and hose barb connections, particularly connections to the feed ports for leak-free connections at high pressure. Safety cautions CAUTION! Hollow fiber cartridges are strong and safe, but mishandling can damage the membrane fibers or cartridge housing connectors. Follow these guidelines to prevent damage to the hollow fibers and cartridge housing connectors: • If ultrafiltration hollow fibers dry out, they can be difficult to rewet. Do not allow ultrafiltration cartridges to dry out. • Dropping cartridges during handling or subjecting the cartridge to pressure surges during use can damage the hollow fibers or housing. Handle cartridges carefully to prevent dropping, and do not expose cartridges to pressure surges during use. • Fittings and connectors are made of plastic and can crack if clamps are overtightened. Do not overtighten sanitary clamps when connecting fittings and components together. CAUTION! Failure to carefully plan the installation of the system can result in equipment damage or poor performance. To avoid equipment damage, carefully plan the installation of the system in reference to the effects of a power failure and utility connections. Read the installation instructions in the system’s user guide. Instructions 18-1174-61 AC 5 2 FlexStand cartridge holder Package contents The standard FlexStand cartridge holder (FS-01S) includes these items: • Stand with supporting rods and manifolds • 0 to 4 barg (0 to 60 psig) pressure gauge • Backpressure control valve (tubing pinch type) • Blank-off cap • Six, 1.5-inch sanitary clamps • Six, 1.5-inch sanitary gaskets (silicone) • Tubing connector kit (KTC-2) • Learning to Use the FlexStand Cartridge Holder user guide • Cross-Flow System Safety: Multilingual Safety Instructions • Certificates of compliance for FlexStand cartridge holder and components Cartridge holder FS-01S-30 includes all the parts above, but a 2-barg (30-psig) pressure gauge is provided in place of the 4-barg (60-psig) pressure gauge. Cartridge holder FS03LVS-30 includes all the parts below, but a 2-barg (30-psig) pressure gauge is provided in place of the 4-barg (60-psig) pressure gauge. The low void volume FlexStand cartridge holder (FS-03LVS) includes these items: • Stand with supporting rods and manifolds • 0 to 4 barg (0 to 60 psig) pressure gauge • Backpressure control valve (tubing pinch type) • Blank-off cap • Six, fractional sanitary clamps • Six, fractional sanitary gaskets (silicone) • Tubing connector kit (KTC-FS-03VS) • Learning to Use the FlexStand Cartridge Holder user guide • Cross-Flow System Safety: Multilingual Safety Instructions • Certificates of compliance for FlexStand cartridge holder and components 6 Instructions 18-1174-61 AC System overview A typical FlexStand cartridge holder setup showing the various components needed for cross-flow filtration with hollow fiber cartridges (Fig 1). 1 Support rod cap 2 Support rod 3 Manifold lock knob 4 Upper (retentate) manifold 5 Cartridge (not supplied) 6 Lower (feed) manifold 7 Feed pressure gauge 8 Support rod base 9 Blank-off cap 10 Permeate line 11 Back pressure control pinch valve 12 Secondary permeate line with pinch clamp Fig 1. Typical FlexStand cartridge holder. Differences between the cartridge holders Compared to the standard FlexStand cartridge holder (FS-01S) the low-void-volume FlexStand (FS-03LVS) cartridge holder has smaller inside diameter manifold ports and tubing. The standard system uses 1.5-inch sanitary connectors and the low-void-volume system uses fractional sanitary connectors. The main components of a FlexStand cartridge holder are: • Supporting rods, base, and manifolds • Pressure gauge • Backpressure control valve • Tubing connector kit The following sections describe these and other key components. Instructions 18-1174-61 AC 7 Supporting rods, base, and manifolds The stand consists of a base plate, supporting rods, and two adjustable slider assemblies with manifolds. The base plate holds the supporting rods which in turn support the slider assemblies and manifolds. The slider assemblies move up and down along the support rods and lock into positions that enable you to mount various length cartridges between the manifolds. The manifolds serves several functions: they direct the flow of process solution into and out of the cartridge and they enable the attachment of the pressure gauges and process tubing. Pressure gauge The FlexStand cartridge holders includes one, 0 to 4 barg (0 to 60 psig) pressure gauge to monitor feed pressure. The mechanically dampened pressure gauge connects to the feed and retentate ports using sanitary connectors. You can order and mount optional pressure gauges to monitor retentate and permeate pressure. Backpressure control valve The FlexStand cartridge holders include a heavy duty pinch valve that enables operators to control the backpressure in the filtration system. The retentate tubing is placed in the clamp and a hand knob enables operators to tighten or loosen the clamp, affecting the backpressure on the system. 8 Instructions 18-1174-61 AC Tubing connector kit The standard FlexStand cartridge holder includes tubing connector kit KTC-2, and the low void volume FlexStand includes tubing connector kit KTC-FS-03VS. The kits contain the clamps, gaskets, and adaptors needed for assembling and operating the system (Fig 2). Fig 2. Tubing connector kits for the standard (left) and low-void-volume (right) Hollow fiber cartridges You order hollow fiber cartridges separately from the FlexStand cartridge holder. Consult our cartridge selection guide, Selecting Hollow Fiber Cartridges and Systems, for a list of cartridges and cartridge specifications such as membrane pore sizes, fiber lumen diameters, cartridge lengths, and membrane areas. Instructions 18-1174-61 AC 9 3 Setting up the cartridge holder Setting up the FlexStand cartridge holder requires choosing a location, assembling the holder, and integrating the holder into a cross-flow filtration system and installing a cartridge into the holder. Choosing a location You should locate your cartridge holder as close as possible to your cross-flow filtration system to minimize tubing runs and hence holdup volume. The location should have appropriate drains or collection vessels to collect waste and processed fluids. The location should be level and sturdy. One commonly used location is on a laboratory bench near a sink. Another is on a heavy-duty stainless steel cart or skid to enable you move the system in and out of wet labs and cold rooms. Unpacking Your FlexStand cartridge holder arrives partially assembled in a single package. Carefully remove all the components from the box. Set them out on a bench or work table and inspect the parts for shipping damage. Assembling the holder The main assembly steps include these: 1 Install the support rods into the base 2 Install the feed pressure gauge 3 Install a hollow fiber cartridge 4 Connect process lines The following sections describe each step. Consult Fig 3 as you complete the instructions. 10 Instructions 18-1174-61 AC . Fig 3. Typical assembly of FS-015 FlexStand cartridge holder. Install the support rods into the base FlexStand cartridge holders are shipped partially assembled. 1 To finish the assembly, gently lay the preassembled support rod assembly on a bench with the manifold assemblies facing up. 2 Slide the support rods into the base plate and fasten with the supplied 5/16-inch hexhead bolts and washers. 3 Position the FlexStand upright. If using a LABTOP rotary lobe pump, position the FlexStand cartridge holder in front of the Labtop pump. Instructions 18-1174-61 AC 11 Install the feed pressure gauge Follow these steps to install the feed pressure gauge: 1 Place a 1.5-sanitary gasket on the front-facing sanitary flange of the lower manifold. 2 Hold and align the pressure gauge flange against the manifold sanitary flange and clamp the gauge in place using a 1.5-inch sanitary clamp. Install a hollow fiber cartridge You can install hollow fiber cartridges with a range of pore sizes and membrane areas in FlexStand cartridge holders: • Cartridges with 1.5-inch sanitary flanges (standard and LVS models) • Cartridges with fractional sanitary flanges (LVS models only) The procedure to install each size of cartridge is described below. Ensure you match the cartridge feed flow requirements to the pump capacity. Installing cartridges with 1.5-inch sanitary endfittings (in FS-01S FlexStand holders) For FlexStand model FS-01S, follow these steps to install a cartridge with 1.5-inch sanitary connectors: 1 Gather these parts: • Cartridge with 1.5-inch sanitary endfittings • Two, 1.5-inch silicone gaskets • Two, 1.5-inch sanitary clamps 12 2 Raise upper manifold so that distance between upper and lower manifolds exceeds cartridge length. 3 Place a gasket on the lower manifold. 4 Place the end of the cartridge on the gasket in the lower manifold and secure with a sanitary clamp. 5 Place a gasket on upper end of cartridge. 6 Loosen the upper manifold and slide it down to mate with gasket and upper end of cartridge. 7 Tighten upper manifold hand knobs to secure the manifold and cartridge in place. 8 Secure the end of the cartridge to the upper manifold with a sanitary clamp. Instructions 18-1174-61 AC Installing cartridges with 1.5-inch sanitary endfittings (in FS-03LVS FlexStand holders) For FlexStand models FS-03LVS, follow these steps to install a cartridge with 1.5-inch sanitary connectors: 1 Gather these parts: • Cartridge with 1.5-inch sanitary endfittings • Two, 1.5-inch silicone gaskets • Two, 1.5-inch sanitary clamps • Two, 1/2-inch silicone gaskets • Two, fractional sanitary clamps • Two, 1.5-inch-to-fractional polysulfone adaptors 2 Raise upper manifold so that distance between upper and lower manifolds exceeds the length of the cartridge and two adaptors. 3 Place a 1/2-inch gasket on the lower manifold. Place one of the adaptors on the gasket and manifold and secure with a sanitary clamp. 4 Place a 1.5-inch gasket on the adaptor. Place one end of the cartridge on the gasket and adaptor and secure with a sanitary clamp. 5 Place a 1.5-inch gasket on the upper end of the cartridge. Place one of the adaptors on the gasket and cartridge and secure with a sanitary clamp. 6 Place a 1/2-inch fractional gasket on the upper end of the adaptor. Loosen the upper manifold and slide it down so that it mates with the gasket and adaptor. 7 Tighten upper manifold hand knobs to secure the manifold, adaptor, and cartridge in place. 8 Secure the end of the adaptor to the upper manifold with a sanitary clamp. Instructions 18-1174-61 AC 13 Installing cartridges with fractional sanitary endfittings (FS-03LVS models only) Follow these steps to install a cartridge with fractional sanitary connectors: 1 Gather these parts: • Cartridge with fractional sanitary endfittings • Two, 1/2-inch silicone gaskets • Two, fractional sanitary clamps 2 Raise upper manifold so that distance between upper and lower manifolds exceeds cartridge length. 3 Place a gasket on the lower manifold. 4 Place the end of the cartridge on the gasket in the lower manifold and secure with a fractional sanitary clamp. 5 Place a gasket on upper end of cartridge. 6 Loosen the upper manifold and slide it down to mate with gasket and upper end of cartridge. 7 Tighten upper manifold hand knobs to secure the manifold and cartridge in place. 8 Secure the end of the cartridge to the upper manifold with a fractional sanitary clamp. Connect process tubing lines Connect process tubing using the supplied adaptors, fittings, tubing clamp, sanitary clamps, and gaskets (Fig 4). There are several lines you must install: •Feed line from the reservoir outlet to the pump inlet •Feed line from the pump outlet to the feed manifold inlet •Retentate line from the upper manifold outlet to the feed reservoir inlet •Two permeate lines •Optional diafiltrate connections to a feed reservoir inlet Use the appropriate adaptors and sanitary clamps to attach your process lines to the manifolds and cartridge permeate ports. Fig 4. Typical cross-flow filtration system setup. 14 Instructions 18-1174-61 AC WARNING! Failure to use tubing clamps to secure hoses on tubing nipple and hose barb fittings can cause unexpected leaks of potentially hazardous fluids and result in bodily harm. To prevent unexpected leaks and possible bodily harm, use tubing clamps on all tubing nipple and hose barb connections, particularly connections to the feed ports for leak-free connections at high pressure. WARNING! If the system leaks, it can release potentially hazardous process fluids or cleaning fluids causing bodily harm. To prevent leaks and the release of potentially hazardous process or cleaning fluids, limit feed pressure to the maximum operating pressure of your system, periodically check parts for wear, and ensure you assemble the components correctly. To monitor system pressure, GE Healthcare recommends that you install pressure gauges on the system as described in the systems’ user guides. Periodically inspect the system’s gaskets, seals, and connections for wear. Ensure you assemble the system correctly following the instructions in the system guide. Wear the appropriate personal protection devices and clothing when operating and cleaning the system. Basic personal protection devices include protective clothing, safety glasses, and hearing protection. Use additional protective devices (fume hood, respirator, etc) if the nature of your product or your company’s safety regulations require it. 4 Operation The operating guide supplied with your hollow fiber cartridge describes how to use GE Healthcare cartridges (flushing, operation conditions, cleaning, etc.) Depending upon the type of hollow fiber cartridge you use and the process objectives, the operation of FlexStand cartridge holder can vary considerably. If you need assistance with application information, contact your GE Healthcare representative Instructions 18-1174-61 AC 15 5 Troubleshooting If the FlexStand cartridge holder does not work properly, consult Table 1. Table 1. FlexStand cartridge holder troubleshooting guide Symptom Leaks at tubing nipple or hose barb connections at permeate ports Possible cause Wrong size tubing, tubing split at hose barb, tubing clamp not installed Process solution leaks from sanitary connections Sanitary connection gasket missing, worn, damaged, improperly mounted, or wrong size Sanitary clamp loose Corrosive process or cleaning solution not flushed from the surface of the holder Stainless steel shows evidence of corrosion Solution Insure tubing ID is sized properly for the connection, check tubing for wear or splitting, ensure hose barb clamp is installed and tight. Inspect gasket for wear, damage, and proper sizing. Reinstall gasket. Tighten sanitary clamp Prevent further corrosion by properly cleaning the FlexStand cartridge holder after use. Flush surface with water and dry with a clean, lint-free cloth. 6 Maintenance Inspection Periodically—based on usage—you should make these inspections: • Check the tightness of the support rod nuts on the bottom of the base. Check the tightness of the support rod cap. Ensure it is fully seated on the rods. • Inspect piping connections for tightness and worn gaskets after each run. WARNING! Inspecting the FlexStand cartridge holder without disconnecting the feed pump power cable, disconnecting the compressed air supply, and decompressing the system, can result in bodily injury from the accidental starting of the pump or unexpected release of pressure. To prevent bodily injury, disconnect the feed pump power cable, disconnect the compressed air line, and depressurize the system before performing inspections and disassembling the system. 16 Instructions 18-1174-61 AC Maintenance The system should be flushed after each use and before storage. When you flush the hollow fiber cartridge after use, you simultaneously flush and clean the FlexStand cartridge holder, thus no further flushing is needed. If the last operation you perform with the cartridge holder is to flush the cartridge with a storage solution, you must then flush the holder with DI water or WFI to remove the storage solution. Position an old cartridge or a short piece of flexible tubing with sanitary adaptors in the cartridge position to flush the system with water. After use, you should wipe down the exterior components of the FlexStand cartridge holder with water to remove dirt and residual process/cleaning solutions. Wipe the system dry with a clean, lint-free cloth. Storing the holder To store the holder for more than a few days, clean it as described in the maintenance section. Drain all rinse water from the system. Remove the cartridge from the FlexStand. Blank off open lines or ports in the system and reservoir. Store the cartridge in accordance with the instructions in the cartridge user guide (in general, well-sealed with ultrafiltration membranes kept wet in storage solution) and stored at cool or ambient temperature. System disposal When the service life of the system is reached, flush the system to remove hazardous process fluids. Dispose of the unit in accordance with the government and environmental regulations that pertain to your location. 7 Specifications Connectors, standard model 1.5-inch sanitary connectors Connectors, low-void-volume fractional sanitary connectors Dimensions, approximate (W × L × H) 25 × 30 × 112 cm (10 × 12 × 44 in.) Weight, approximate 13.6 kg (30 lbs) Materials of construction 316L stainless steel, anodized aluminum, rubber Instructions 18-1174-61 AC 17 8 Further information This user guide belongs to a set of documents that are available for GE Healthcare hollow fiber membrane products. You can download technical documents and learn more about hollow fiber membrane cartridges and cross-flow systems by visiting our website, www.gehealthcare.com. Related documents • Selecting Hollow Fiber Cartridges and Systems Describes the entire range of microfiltration and ultrafiltration pore sizes, cartridge sizes and benchtop systems available from GE Healthcare. Describes how to select cross-flow cartridges. • Operating Guide for Hollow Fiber Cartridges and Systems Describes operating details for hollow fiber cartridges. Includes start-up, cleaning and storage conditions as well as autoclave procedures and chemical compatibility. An excellent primer on the effects of concentration, time, temperature and flow rate on membrane cartridge performance. • Integrity Test Procedure Guide Step by step instructions on the basic tests used to confirm membrane integrity: pressure hold, air diffusion, bubble point and water flux. • Validation Guide Provides background data on materials of construction for hollow fiber membrane cartridges. Results of USP safety tests for plastics are also included. 18 Instructions 18-1174-61 AC 9 Spare parts and accessories Code number Model number 56-4107-54 FS-01S 56-4107-56 56-4107-57 56-4107-58 56-4107-55 56-4107-59 56-4107-63 56-4107-67 56-4107-70 56-4107-69 56-4107-62 56-4107-61 56-4107-64 56-4107-65 56-4106-03 56-4106-04 56-4106-06 56-4107-72 56-4107-73 56-4105-92 56-4105-93 Description Standard FlexStand benchtop pilot system with 1.5-in Tri-Clamp connections FS-02RLP Standard FlexStand benchtop pilot system with 1.5-in Tri-Clamp connections, rotary lobe pump FS-02RLP/50 Same as FS-02RLP except with 230-volt, 50-Hz electrical system FS-04LVS-RLP Low void volume FlexStand benchtop pilot system with fractional Tri-Clamp connections, rotary lobe pump FS-03LVS Low void volume FlexStand benchtop pilot system with fractional Tri-Clamp connections FS-04LVS RLP/50 Same as FS-04LVS-RLP except with 230-volt, 50-Hz electrical system TK01-30SS Stainless steel tank, ASME code, adjustable legs, electropolished, 30-liter capacity, sanitary ports for retentate return, vent filter and continuous diafiltration. Withstands up to 275°C for steam sterilization. FRV-2A 2-liter polysulfone reservoir kit with sealable top, autoclavable FRV-5A 5-liter polysulfone reservoir kit with sealable top, autoclavable FRV-CP2-5A Replacement cap for 2- and 5-liter polysulfone reservoirs, autoclavable KFSM04 Conversion kit to change standard FlexStand to low void volume assembly KFSM12 Conversion kit to change low void volume FlexStand to standard assembly KTC-2 Tubing connector kit for FS-01S KTC-FS-03VS Tubing connector kit for FS-03LVS PG-TCP30 Pressure gauge, 0-2 barg (0-30 psig), mechanically dampened, autoclavable PG-TCP60 Pressure gauge, 0-4 barg (0-60 psig), mechanically dampened, autoclavable PG-TCV30P30 Vacuum pressure gauge -2 to 2 barg (-30 to 30 psig), mechanically dampened, autoclavable KDV-F1 Drain valve kit for FS-01S, includes custom tee, sanitary plug valve, gasket and clamp KPCM-1 Manual permeate control kit, includes vacuum pressure gauge, backpressure valve, supports, adaptors, clamps and gaskets VDM-6SS Diaphragm valve, fractional Tri-Clamp, stainless steel VDM-12SS Diaphragm valve, 1.5-in Tri-Clamp, stainless steel Instructions 18-1174-61 AC 19 For contact information for your local office, please visit: www.gelifesciences.com/contact GE Healthcare Bio-Sciences AB Björkgatan 30 751 84 Uppsala Sweden www.gelifesciences.com/filtration GE, imagination at work and GE monogram are trademarks of General Electric Company. FlexStand is a trademarks of GE Healthcare companies. © 2008 General Electric Company—All rights reserved. All goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them. A copy of these terms and conditions is available on request. Contact your local GE Healthcare representative for the most current information. GE Healthcare UK Ltd Amersham Place, Little Chalfont, Buckinghamshire, HP7 9NA, UK GE Healthcare Bio-Sciences Corp 800 Centennial Avenue, P.O. Box 1327, Piscataway, NJ 08855-1327, USA GE Healthcare Europe GmbH Munzinger Strasse 5, D-79111 Freiburg, Germany GE Healthcare Bio-Sciences KK Sanken Bldg. 3-25-1, Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan imagination at work 18-1174-61 AC 04/2008
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