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Multifors 2 - Parallel Bench-top Bioreactor

Setup and Function

28 March 2018

Page

211



Magnetic stirrer for bacteria or cell cultures. For details on stir-

rers, see chapter "Drive and Stirrer".

1400 mL vessels for bacterial cultures are all equipped with a baf-

fle cage. For details see the chapter “Baffle Cage”.

Summary of Contents for Multifors 2

Page 1: ...Operating Manual 2018 03 28 Multifors 2 Parallel Bench top Bioreactor Dok ID V 04 01 Original...

Page 2: ...t com Infors USA Inc 9070 Junction Drive Suite D Annapolis Junction MD20701 T 1 301 362 3710 T 1 855 520 7277 toll free USA F 1 301 362 3570 infors usa infors ht com www infors ht us Infors Canada 835...

Page 3: ...uthorised Persons 15 2 3 Conventional Use of the Equipment 16 2 4 Personal Protective Equipment 17 2 5 Particular Hazards 19 2 6 Environmental Protection 22 2 7 Adhesive Labels Signs Symbols 22 3 Tech...

Page 4: ...52 4 2 2 Operating Panel Connections 53 4 3 Vessels Vessel holder Transport Frame 54 4 3 1 Vessel for bacterial Cultures 55 4 3 2 Vessel for Cell Cultures 57 4 3 3 Baffle Cage 58 4 3 4 Vessel Top Plat...

Page 5: ...Location Requirements for Installation 94 6 2 1 General Information 94 6 2 2 Minimum Spacing 95 6 2 3 Supply Lines 95 6 2 3 1 Air Gas 95 6 2 3 2 Exit Gas 96 6 2 3 3 Water Inlet 97 6 2 3 4 Water outle...

Page 6: ...tion in the Autoclave 143 7 3 1 Sterilisation Methods 143 7 4 Preparations after Sterilisation 146 7 4 1 Mounting the Vessel Holder with the Vessels on the Basic Unit 146 7 4 2 Filling the reagent Hos...

Page 7: ...193 9 6 2 Vessel Top Plate 194 9 6 3 Exit Gas Cooler 195 9 6 4 Reagent Bottles and Hoses 195 9 6 5 Sensors 196 9 6 6 Operating Unit 197 10 Interferences 198 10 1 Safety 198 10 2 Tables of Interference...

Page 8: ...erators at all times The operators must read thoroughly and fully understand this manual before commencement of any work Adhering to all the points advice and instructions concerning safety and operat...

Page 9: ...of prop erty DANGER Points out an immediate dangerous situation that leads to death or severe injuries unless avoided WARNIG Points out a potentially dangerous situation that may lead to death or sev...

Page 10: ...vere or fatal physical injury WARNING Danger of infectious substances signifies danger by infectious substances e g liquids which contain bacteria or viruses Non ob servance of safety instructions ma...

Page 11: ...ope of delivery may differ from the explanations descrip tions and figures in this operating manual due to additional options specified on ordering and the latest technical mechanical modifica tions O...

Page 12: ...rantee The terms of the guarantee are included in the manufacturer s gen eral conditions of business contract to supply 1 7 Customer Service Our customer service is at your disposal for technical advi...

Page 13: ...assessment to identify additional hazards due to special working conditions related to the equipment s area of application They must de clare these hazards in the form of directives for the equip ment...

Page 14: ...tandards and regulations Qualified personnel are capable of carrying out the assigned work identifying and avoiding possible hazards independently due to their professional standing experience skills...

Page 15: ...persons are those who do not fulfil the criteria described here and so may not appreci ate any of the dangers related to operation Therefore Keep unauthorised people away from the area of operation C...

Page 16: ...non conventional use is considered as misuse and may lead to dangerous situations WARNING Danger by misuse Misuse of the equipment may lead to dangerous situations In particular desist from using the...

Page 17: ...all activities Protective clothes To protect against contamination and carryover of viable organ isms Must be tight fitting and only slightly tear proof work clothes with tight sleeves and no loose m...

Page 18: ...inst liquid splashes Protective gloves chemical resistant To protect hands from aggressive substances Check gloves are impermeable before use Clean gloves before taking them off and store in a well ve...

Page 19: ...supply when the insulation is damaged and initiate a repair Only qualified electricians are allowed to make these repairs on the electrical system Disconnect electrical components from the mains supp...

Page 20: ...NING Danger of scalding and burns due to contact with hot surfaces Skin contact with hot surfaces can lead to severe scalding and burns Therefore Always wear protective clothes and heat re sistant glo...

Page 21: ...high health risk for the user depending on the type of gases used Therefore Strictly adhere to safety regulations regarding the use and handling of dangerous gases Strictly follow the instructions in...

Page 22: ...ntally Inform the responsible local authority if in doubt Organisms and genetically modified materials must not gain ac cess to the environment They must be disposed of in accordance with local regula...

Page 23: ...ious materials are handled Immediately call a doctor if suspicion of infection arises Corrosive substances Risk of chemical burns A chemical burn to the eyes may lead to irreparable eye injuries Chemi...

Page 24: ...Multifors 2 Parallel Bench top Bioreactor Technical Data Page 24 of 211 28 March 2018 3 Technical Data 3 1 Equipment Dimensions Dimensions in mm...

Page 25: ...Depending upon height of the culture vessels the height of the frame which houses them is adjustable Dimensions Vessels Total volume 0 4 l Bact Cell 0 70 l Cell 0 75 l Bact 1 0 l Cell 1 4 l Bact A 18...

Page 26: ...Multifors 2 Parallel Bench top Bioreactor Technical Data Page 26 of 211 28 March 2018 Top View Dimensions in mm apply to all vessel sizes...

Page 27: ...op Bioreactor Technical Data 28 March 2018 Page 27 of 211 3 3 Weights Description Value Unit Touch screen operating panel 5 kg Basic unit with 2 culture vessels equipped with standard compo nents and...

Page 28: ...4 8 A 3 4 2 Water IN Description Value Unit Connection pressure 2 1 bar Temperature min 1 C Connection hose nozzle outer diameter 8 3 mm 3 4 3 Water OUT Description Value Unit Connection pressure No b...

Page 29: ...ltifors 2 Parallel Bench top Bioreactor Technical Data 28 March 2018 Page 29 of 211 3 4 5 Exit Gas Description Value Unit Connection pressure no back pressure Connection hose nozzle outer diameter 5 m...

Page 30: ...ssels General Description Value Material Borosilicate glass Form Bacterial system flat bottom Cell culture system round bottom Bacterial system TV WV max WV min NW Height 400 mL 250 mL 100 mL 70 55 mm...

Page 31: ...s bacterial system Port Number vessel size NW Thread 400 mL TV 750 mL TV 1400 mL TV 7 mm Without 4 4 4 10 mm Without 4 4 4 12 mm Pg13 5 3 4 5 Vessel top plate ports cell culture system Port Number ves...

Page 32: ...ange of rotation speed with 2 impel lers2 Vessel 400 mL and 750 mL TV 100 up to 1600 min 1 Vessel 1400 mL TV 100 up to 1500 min 1 Accuracy Measurement 5 min 1 at 100 up to 1000 min 1 1 setpoint at 100...

Page 33: ...00 mL 38 mm 9 0 mm 11 mm The figure to the left shows the Rushton impeller 3 5 4 Stirrer Drive System Cell Culture Version Description Value Drive Magnetic Motor Type Stepper motor Nominal power 8 3 W...

Page 34: ...2018 Impellers Type und Material Number Vessel Pitched blade impeller 3 blades 316L electro polished Ra 0 8 m Angle of 45 producing an upward flog 2 pieces 400 mL 1 piece 700 mL 1000 mL Vessel A B C...

Page 35: ...PT 100 1 3 DIN B Heating Electric thermal block 315 W Cooling With tap water or chiller via thermal block default With cold finger in 12 mm port op tion Measuring range 10 C up to 150 C Control range...

Page 36: ...low control Accuracy MFC Gas mix control Air 1 MFC 1 Air O2 1 MFC 2 solenoid valves Air N2 1 MFC 2 solenoid valves Air O2 N2 1 MFC 3 solenoid valves Variant High End Gas Gas flow control Accuracy MFC...

Page 37: ...variant 0 1 min 1 For head space gassing this rate is 1 min 1 for each vessel size and variant Variant Standard Gas es Gas flow control Accuracy MFC Gas mix control Air 1 MFC 0 3 final value 0 5 meas...

Page 38: ...to 0 64 5 0 up to 80 0 0 75 L 0 80 up to 80 0 0 06 up to 0 98 3 5 8 Antifoam Description Value Sensor Conductive with dosing needle Control Peristaltic pump AF Antifoam Range 0 100 ON OFF 3 5 9 pH Des...

Page 39: ...Control Cascaded stirrer Cascaded flow Cascaded gasmix Cascaded O2 addition The functionality of the parameters depends on the hardware configuration of the equipment Variants Mess System Sensor optio...

Page 40: ...ogue 1 piece Feed Option 1 or several free standing pumps analogue Rotation speed Digital 74 min 1 fixed rotation speed Analogue 74 min 1 max rotation speed adjustable within range of 0 up to 100 Accu...

Page 41: ...11 3 5 12 Sterile Filters Description Value All filters Autoclavable Disposable Inlet air filter red label Retention rate 0 2 m Diameter 37 mm Inlet air filter no label Retention rate 0 2 m Diameter 2...

Page 42: ...oreactor Technical Data Page 42 of 211 28 March 2018 3 6 Operating Conditions Description Value Unit Range of temperature 5 to 40 C Relative humidity non condensing 20 to 90 3 7 Emissions Description...

Page 43: ...owing information Designation Device designation category Type Model Type Name S N Serial number Year Year of manufacture Mains Nominal voltage and frequency Current Current consumption Manufacturer a...

Page 44: ...Unit 1 Equipment frame 2 Measuring amplifier 3 Hand grip basic unit 1 x left 1 x right 4 Pumps 5 Thermal block 6 Vessel holder and support frame 7 Main switch Two vessels bioreactors of the same size...

Page 45: ...measuring amplifiers with an integrated temperature sensor Pt100 and con necting cables for the pH pO2 and antifoam sensors The sensor cables not visible in the illustration above are ar ranged in th...

Page 46: ...in Switch The main switch is a green rocker type It is located at the top left on the front of the basic unit and is marked POWER The main switch is illuminated when the equipment is switched on 4 1 2...

Page 47: ...ut water outlet Water in water inlet 4 1 4 Gas Connections The connections for air gas are located at the top on the back of the basic unit The number of connections depends on the equip ment configur...

Page 48: ...utlet of exit gas cooler respectively water inlet of basic unit The control valves for the water flow are labelled with an icon The valves are preset in the factory If necessary the water flow rate ca...

Page 49: ...Setup and Function 28 March 2018 Page 49 of 211 4 1 6 Connection of the Sparger The hose nozzles to connect the sparger to the gassing are lo cated beneath the rotameter mounted on the unit s frame n...

Page 50: ...s follows Acid Base AF antifoam Feed When the basic unit is switched on the pumps can be operated manually with the rocker switch as follows Press the rocker switch to the right side and hold The moto...

Page 51: ...Bioreactor Setup and Function 28 March 2018 Page 51 of 211 Feed solution can also be added via an additional analogue pump This is mounted on the side of the basic unit Several free standing pumps can...

Page 52: ...en software can be found in the separate manual 4 2 1 Monitor Keys Four monitor keys are situated on the upper left side of the touch screen operating panel 1 ON OFF key 2 DECREASE brightness key to s...

Page 53: ...entation When pressing the ON OFF key when the bioreactor fer mentation is stopped a dialogue box for shutting down the system appears 4 2 2 Operating Panel Connections Five connectors labelled with d...

Page 54: ...silicate glass All ves sels are delivered with a pre assembled top plate in a stainless steel vessel holder and transport frame Vessel holder and transport frame The vessel holder and transport frame...

Page 55: ...r are available as an optional extra 4 3 1 Vessel for bacterial Cultures Flat bottom vessels for bacterial cultures are available in three sizes 400 mL total volume nominal diameter 70 55 750 mL total...

Page 56: ...Multifors 2 Parallel Bench top Bioreactor Setup and Function Page 56 of 211 28 March 2018 The flat bottom vessels are available with a GL1 4 port at the bot tom of the vessel as an optional extra...

Page 57: ...und bottom vessels for cell cultures are available in two sizes 700 mL total volume nominal diameter 70 1000 mL total volume nominal diameter 90 Additionally available Flat bottom vessel 400 mL total...

Page 58: ...n Page 58 of 211 28 March 2018 4 3 3 Baffle Cage 1400 mL vessels for bacterial cultures have a baffle cage as a standard fitting The cage is made in two pieces that are held together with two cheese h...

Page 59: ...l Bench top Bioreactor Setup and Function 28 March 2018 Page 59 of 211 A baffle cage is also available for 750 mL culture vessels as an op tion It is made in one piece and is permanently welded onto t...

Page 60: ...iguration The vessel top plate has different ports of different sizes to mount the different components such as sparger blanking plugs sensors etc The vessel top plate is equipped with A clamping ring...

Page 61: ...ews are used to secure the blanking plugs 4 addition port adapters with O rings for reagents The addition port adapters have an oblique tip The long sides of the needle tips must all face outwards see...

Page 62: ...ead screw to secure it Holder for reagent bottle hoses The hose holder is also used to secure the addition port adapters Before the inlet needle can be removed from the top plate the wire holder must...

Page 63: ...nction 28 March 2018 Page 63 of 211 Magnetic stirrer for bacteria or cell cultures For details on stir rers see chapter Drive and Stirrer 1400 mL vessels for bacterial cultures are all equipped with a...

Page 64: ...e with nominal Width 55 70 1 12 mm Pg13 5 Exit gas cooler 2 12 mm Pg 13 5 Sparger 3 12 mm Pg 13 5 pH Sensor 4 10 mm Dip tube for sampling 5 10 mm Temperature sensor Pt100 6 7 mm Addition port adapter...

Page 65: ...ominal Width 70 1 10 mm Sparger 2 12 Pg13 5 mm Exit gas cooler 3 7 mm Addition port adapter 4 pieces 4 10 mm Temperature sensor Pt100 5 12 Pg 13 5 mm Inoculation 6 12 mm Pg13 5 pO2 sensor 7 Ground for...

Page 66: ...90 1 12 Pg 13 5 mm pO2 sensor 2 10 mm Sparger 3 12 Pg 13 5 mm Exit gas cooler 4 7 mm Addition port adapter 4 pieces 5 10 mm Temperature sensor Pt100 6 12 Pg 13 5 mm Inoculation 7 12 Pg 13 5 mm pH sens...

Page 67: ...ed using a dry system comprising two thermal blocks made of aluminium Cooling is carried out via a heat exchange system in the thermal block The block for each vessel is fed separately with coolant wa...

Page 68: ...The power is transferred via ring magnets Two are located on the drive shaft and two on the encapsulated motor shaft below the cul ture vessel in the basic unit 4 5 1 Drive Shaft for bacterial Cultur...

Page 69: ...mL vessels are equipped with four magnets as well as a centring plate 4 5 2 Drive Shaft for Cell Cultures 1 Magnet holder 2 Magnet The illustration on the left shows the lower section of a drive shaft...

Page 70: ...0 mL vessels two blade impellers with 6 blades made of 316L are used here The standard stirrer for cell cultures has pitched blade impellers with 3 blades that produce an upward flow The number of imp...

Page 71: ...assing System 1 Rotameter 2 Manometer 3 Pressure reducing valve The basic unit is equipped with the appropriate gassing units rota meter solenoid valves mass flow controllers and configured ac cording...

Page 72: ...ia solenoid valves High End Gas flow control and Gasmix via electronic mass flow controllers 1 piece per gas Additionally for cell cultures available Head space gassing with Air Manual gas flow contro...

Page 73: ...s for bacterial cultures 700 mL vessels for cell cultures 1000 mL vessels for cell cultures Sparger with aeration ring 1 Sparger 2 Aeration ring 3 Centring plate The sparger is connected to an aeratio...

Page 74: ...2018 The illustration on the left shows the lower section of a sparger with the aeration ring as well as the drive shaft with location bearing and magnets Details of the drive shaft are given in chap...

Page 75: ...he left shows the lower section of a ring sparger along with the drive shaft and location bearing magnets centring plate etc for a 1400 mL vessel for bacterial cultures Details of the drive shaft and...

Page 76: ...humidity in the exit gas filter The exit gas cooler is delivered ready assembled 1 Disposable filter with green marking 2 Pressure hose 3 Non adjustable hose clamp 4 Adjustable hose clamp A piece of...

Page 77: ...m Sensor The antifoam sensor detects foam and serves as a dosing needle for the antifoam reagent at the same time When the sensor comes in contact with foam or liquid an electrical circuit is made and...

Page 78: ...d Function Page 78 of 211 28 March 2018 Type with clamping adapter for 10 mm ports 1 Clamping adapter 2 Dosing needle 3 Round sensor needle tip The antifoam sensor can be adjusted in its height after...

Page 79: ...th thread 3 Dosing needle 4 Sharp sensor needle tip The antifoam sensor can be adjusted in its height after loosening the hollow screw The antifoam sensor is equipped with two protective caps NOTICE T...

Page 80: ...ptionally other reagent bottles are available too One bottle provides reagents or feed solution for two vessels 2 bioreactors 1 basic unit The reagent bottles are delivered fully equipped 1 Needle 2 S...

Page 81: ...cultures Only function and handling of this system is described in this oper ating manual 4 7 3 1 Super Safe Sampler aseptic Sampling System Al Content of the set The aseptic sampling system Super Sa...

Page 82: ...vessel Principle of function Liquid culture samples are taken from the sidearm of the T piece with the Luer fitting using a syringe The Luer activated automatic sample valve opens by putting the Luer...

Page 83: ...mall vessels and or frequent sampling The dead volume of the culture remaining in the group of valves after flushing with sterile air amounts to a few l and is negligibly small therefore in relation t...

Page 84: ...to 60 mL volume are available from laboratory suppliers NOTICE The use of a syringe with Luer push fit is also pos sible However a syringe with a Luer lock prevents unwanted movement of the syringe A...

Page 85: ...nfection of the sam ple valve Spray a commercially available disinfectant onto the valve leave to soak and then wipe off with a sterile cloth Possibilities of modification Super Safe Sampler 1 Adapter...

Page 86: ...iece 3 Screw the sample valve without adapter directly onto the check valve Modified Super Safe Sampler The system allows now addition of liquids without allowing remov ing liquids If addition and rem...

Page 87: ...it is particularly suitable for screening tasks Precisely defined fermentation conditions enable the execution of parallel experiments 4 9 Types The equipment is available in four types Multifors 2 fo...

Page 88: ...as during in house transportation Observe all symbols in structions on the packaging Remove packaging finally only when the equip ment is ready to be brought into use 5 2 Transport Inspection Immediat...

Page 89: ...g materials The packaging is the property of the purchaser on delivery Hence the purchaser is obliged to dispose of it appropriately Dispose of packaging materials according to legal statutory regu la...

Page 90: ...ift or a hand pallet truck for transpor tation Make all necessary safety arrangements to pro tect the equipment against falling off Transport of the wooden crate with a fork lift The wooden crate can...

Page 91: ...fresh or renew materials as necessary Store in disassembled condition when storing for more than 1 month Decontaminate and clean the equipment before each storage see the main chapter Maintenance Sto...

Page 92: ...les and hoses Damaged re agent hoses and elements of the bottle caps are a safety risk for the user when operating the equip ment Therefore Never store unwashed reagent hoses and bot tles Thoroughly r...

Page 93: ...rried out by the manufacturer s associates only Call the manufacturer when any subsequent translocation is foreseen Prevent arbitrary installation and translocation 6 1 Safety Personnel Installation a...

Page 94: ...must be installed profession ally Secure component parts so that they cannot fall off or tumble 6 2 Location Requirements for Installation 6 2 1 General Information The following conditions must appl...

Page 95: ...ntains a risk of ex plosion or asphyxiation and a health risk for the user Therefore Only use pressure resistant and intact hoses Preferably use short hoses Ensure hose connections are made carefully...

Page 96: ...wing conditions Conditions gas supply Pressure regulation respectively reduction 2 0 5 bar Manometer for primary pressure control Constancy of gas supply Only use clean dry oil and dust free air gases...

Page 97: ...led water can be used as an alterna tive for cooling purposes Cooling water at a primary pressure of 2 1 bar is appropri ate F r Frag en NOTICE Contact your licensed dealer or the manufacturer for que...

Page 98: ...onnection to be made by a qualified electrician only Conditions The electric power supply must meet the following conditions Single phase power supply Type 230 V 230 V 50 60 Hz Type 115 V 115 V 60 Hz...

Page 99: ...clamps on the equipment frame 1 Mounting plate 2 Flanged clamp 3 Equipment frame The mounting plate is mounted on the operating panel in the fac tory The flanged clamps are mounted on the equipment fr...

Page 100: ...nel connections of the main chapter Setup and Function The flat connector of the iDDC bus cable display cable is already connected to the controller inside the basic unit It is imperative that the rou...

Page 101: ...he following connections Connect the water feed and return of the master unit to the water feed and return of each satellite unit using pressure hoses Connect the circuit board controller of the maste...

Page 102: ...total of three units 1 master unit and 2 satellite units 1 Plate with push in bulkhead connectors la belled Water in Water out 2 Hose nozzles for the water connectors 3 Pressure hose black 4 Push in...

Page 103: ...les into the bulkhead connectors on the plate attached to the master unit 2 Connect the pressure hoses together using the push in T con nectors 3 Connect the pressure hoses via the push in T connector...

Page 104: ...or pull out the plug Connect the iDDC satellite cable s to the circuit boards control lers on the rear panel inside the housing of the basic units The illustration below shows from left to right the...

Page 105: ...DC satellite cable already connected to the upper circuit board of the master unit and one to the first satellite unit The other end of each iDDC satellite cable hangs out of the cable hole in the rea...

Page 106: ...heir handling are given in the corresponding chap ters of the main chapter Preparations for Use The touch screen software is described in detail in the separate manual Before starting the test run che...

Page 107: ...vessel to the air supply of the basic unit hose nozzle beneath the rotameter CAUTION Greatly exceeding of the set point due to turned off gas supply If the gas supply to the active mass flow controlle...

Page 108: ...ically and the system boots up 10 Select the bioreactor 11 Open the start dialog 12 Set a low setpoint value e g 10 C for the temperature pa rameter 13 Switch on the temperature parameter All other pa...

Page 109: ...itial Operation 28 March 2018 Page 109 of 211 If the heating system is also working the test is complete 17 Stop the bioreactor 18 Shut down the system 19 Switch off the equipment at the main switch 2...

Page 110: ...use may only be carried out by qualified personnel in biology biotechnology or chemical engineering Inappropriate preparatory work WARNING Risk of injury due to inappropriate preparatory work Inapprop...

Page 111: ...them out of opera tion Adhere to the correct rates in Amps when replacing fuses Keep components which are electrically pow ered away from humidity as excessive moisture may lead to short circuit Do no...

Page 112: ...om the vessel holder with out disconnecting the cable connections between the different sensors and equipment or without re moving the temperature sensor from the pocket in the vessel top plate can da...

Page 113: ...ally out of the thermal block and put aside on a stable clean workspace Removing the vessel top plate To remove the vessel top plate proceed as follows Procedure 1 Hold the vessel tightly with one han...

Page 114: ...ed clamping ring is changed using the screw at the end of the bolt the sealing of the vessel top plate cannot be guaran teed anymore This carries a risk of contamination and loss of property Therefore...

Page 115: ...are present undamaged and correctly seated Damaged O rings must be replaced Carry out this check as follows Procedure 1 Check the top plate gasket O ring for damage Replace if necessary 2 Check the to...

Page 116: ...O rings the component parts can be remounted Please pay attention to the following regarding the addition port adapters The long sides of the needle tips must all face outwards see the il lustration...

Page 117: ...aring CAUTION Danger of damaging the location bearing due to a misplaced stirrer shaft If not seated centrally on the location bearing the stirrer shaft can be abruptly be drawn in by the magnets and...

Page 118: ...rub screws using an Allen key do not fully unscrew 2 Carefully pull the impellers into the desired position 3 Carefully tighten both grub screws again Replacing the vessel top plate To replace the ves...

Page 119: ...tifors 2 Parallel Bench top Bioreactor Preparations for Use 28 March 2018 Page 119 of 211 2 Fit the clamping ring around the vessel top plate and turn the threaded bolt so that it can be hooked in aga...

Page 120: ...proceed as follows Procedure 1 Insert the vessel in the vessel holder and transport frame 2 Hold the vessel holder and transport frame using the grips on either side and place it onto the thermal bloc...

Page 121: ...nce buffer It also applies that the calibration should be performed again before each fermentation cultivation process Calibration must be performed prior to sterilisation in other words before mounti...

Page 122: ...r autoclaving contains a risk of contamination Depending on length of the sensor and size of the vessel the use of a height adjustable electrode holder is necessary For details see the following detai...

Page 123: ...to the threaded collar with the thread point ing in the downward direction 5 Fit the fork of the rod into the groove of the threaded collar 6 Push the threaded collar and the rod together upwards and...

Page 124: ...pletely tighten the grub screw in the support guide with the key pH FINALLY Cover connectors of the sensors from the manufacturer METTLER with a little aluminium foil CAUTION Risk of damage to HAMILTO...

Page 125: ...essel once mounted due to risk of contamination CAUTION Risk of damage Adjusting the height of the antifoam sensor with a tight clamping screw or screw on the clamping adapter can damage the transpare...

Page 126: ...g the hexagon socket spanner provided with the equipment 4 Carefully insert the antifoam sensor into the vessel top plate port 5 Fixate the antifoam sensor in the port Antifoam sensor with clamping ad...

Page 127: ...clamping adapter 12 mm ports b Carefully and manually loosen the hollow screw 7 Adjust the antifoam sensor in its required height Ensure that the sensor head does not touch the clamping adapter respec...

Page 128: ...with corrective reagents Always secure reagent hoses with cable ties Only sterilise reagent bottles that are equipped with a short and open hose line fitted with a clean and dry filter for pressure eq...

Page 129: ...d secure them with cable ties 2 Cut off two longer pieces of silicone hoses per pump The hoses must be long enough to reach from the pumps to the reagent bottles and to the addition port adapters of t...

Page 130: ...e left pump hose intake side see direction of ro tation of the pump in the picture on the left on both pump heads e g both acid pumps 9 Secure the silicone hoses with cable ties Connection of pumps to...

Page 131: ...n of the reagent bottles to the pumps e g acid with acid pump etc 14 Hang the reagent bottles onto the vessel holder using the slots provided The picture on the left shows an empty reagent bottle and...

Page 132: ...s securely fitted before re moving the syringe from the sample valve CAUTION Risk of contamination due to leakages from the sampling system Loose screw connections between the component parts of the s...

Page 133: ...edure 1 Loosen and remove the screw next to the blanking plug in the 10 mm port with a slotted screwdriver no 3 2 Pull the blanking plug out of the port and remove it 3 Loosely insert the dip tube int...

Page 134: ...to the dip tube The hose can be secured with a cable tie for additional secu rity NOTICE Hoses filled with water during sterilisation in the au toclave makes for better heat transfer and thereby redu...

Page 135: ...ntly turn the air filter clock wise 9 Loosely cover the valve assembly with aluminium foil The cover protects the air filter against condensation and keeps the surface of the automatic valve sterile a...

Page 136: ...le with a blocked exit gas line due to kinking or clamping off or a blocked exit gas filter This may lead to overpressure in the vessel which can cause severe injuries or loss of property Therefore En...

Page 137: ...r inoculation with the syringe Proceed as follows Procedure 1 Loosen and remove the blanking plug from the 12 mm port us ing the hexagon socket spanner provided with the equipment 2 Ensure there is no...

Page 138: ...rallel Bench top Bioreactor Preparations for Use Page 138 of 211 28 March 2018 6 Fit the blanking plug into the septum collar 7 Tighten the blanking plug using the hexagon socket spanner provided with...

Page 139: ...is not clamped off entirely The inlet filter will get defective and will need replacement in that case Therefore Ensure the inlet air silicone hose is well clamped off The sparger must be equipped wit...

Page 140: ...arch 2018 4 Fit the inlet filter filter with red label in the air flow direction on the hose The red label INLET must be on the top 5 Loosely secure the inlet air filter with a cable tie 6 Close the c...

Page 141: ...holder and support frame Proceed as follows Procedure 1 Pull off and remove the cover plate from the pump heads NOTICE The cover plate serves only as a protective device in operating mode It is not he...

Page 142: ...er and support frame and can be transported to the autoclave Proceed as follows Procedure 1 Compress both clamps of the snap closure between the ther mal blocks until they are engaged The vessel retai...

Page 143: ...process thoroughly Sterilise for a minimum of 30 minutes at a rec ommended minimum of 121 C Respect custom designed sterilisation condi tions Strictly follow local safety procedures CAUTION Risk of d...

Page 144: ...nsor fits into pocket in the top plate Never take the vessel out of the autoclave at a temperature higher than 80 C Fill the vessel with the culture medium Sterilise the vessel Add sterile water and a...

Page 145: ...it Therefore Never sterilise a completely empty and dry ves sel Fill the vessel with a little water approx 10 mL per litre of working volume to generate sufficient steam in the vessel dur ing sterilis...

Page 146: ...ation in the autoclave carries a severe risk of scalding and burns due to the still hot surfaces Therefore Let the whole unit of vessel holder vessels etc cool down after sterilisation Always wear pro...

Page 147: ...el retaining brackets i e release the clamps of the snap closure between the thermal blocks For this hold both clamps pressing the left hand clamp in wards at the same time NOTICE Do not pull the righ...

Page 148: ...Multifors 2 Parallel Bench top Bioreactor Preparations for Use Page 148 of 211 28 March 2018 6 Fit the hoses behind the hose retainer...

Page 149: ...ght side the pump runs forward counter clockwise reagent is sucked in from the reagent bottle and is pumped in the direction of the vessel Press the rocker switch to the left side the pump runs backwa...

Page 150: ...eed as follows Procedure 1 Cut off piece of thick walled silicone hose The hose must be long enough to reach from the sparger to the gas supply on the basic unit without tension or kinks 2 Fit the sil...

Page 151: ...r Use 28 March 2018 Page 151 of 211 7 4 4 Connecting the Temperature Sensor The temperature sensor Pt100 has no connector To connect it proceed as follows Procedure 1 Insert the temperature sensor as...

Page 152: ...edure 1 Switch on the equipment at the main switch 2 Select the bioreactor whose antifoam pump will be tested in the selection bar 3 Start the bioreactor 4 Switch on parameter antifoam NOTICE For oper...

Page 153: ...op Bioreactor Preparations for Use 28 March 2018 Page 153 of 211 Procedure 1 Insert the red banana connector into the hole in the sensor head 2 Insert the black banana connector into the ground connec...

Page 154: ...cables can be damaged by buckling or twisting This may lead to faulty measurements Ensure that the sensor cables are not buckled or twisted when connecting them Depending on the present measuring sys...

Page 155: ...nnect the sensor cable the red mark on the cable connector and on the sensor connector must be aligned Example HAMILTON ARC sensor with sensor cable to plug on and screw tight The cable has a red prot...

Page 156: ...raphic METTLER pO2 sensors or HAMILTON pO2 sensors of the type Visiferm DO ARC Generally it applies that calibrating the pO2 sensor should be per formed after sterilisation because sterilisation can c...

Page 157: ...en carries a risk of explosion This may lead to se vere injury and loss of property Therefore Ensure safe routing of the exit air WARNING Risk of overpressure in the vessel during fer mentation Pressu...

Page 158: ...e adjustable hose clamp so that the exit gas filter will serve as a predetermined breaking point if necessary 3 Push the coupling nipples of the pressure hoses into the con nection on the front side o...

Page 159: ...o a mains power supply Damage to insulation or components may have fatal conse quences Therefore Never open the housing of the basic unit when the electrical supply is turned on Immediately turn off t...

Page 160: ...the supply is opened Always check the gas supply is closed before removing the gas supply hose from the base unit to the vessel Always close the gas supply if the equipment is not in use Always obey a...

Page 161: ...ays wear protective clothing and safety gog gles Always secure corrective reagent hoses with cable ties Faulty glass WARNING Risk of injury due to faulty glass Faulty glass vessels reagent bottles and...

Page 162: ...ee and not kinked Ensure the screw of the hose clamp on the exit gas hose is slightly loosened so that the exit gas filter can serve as a predetermined break ing point if necessary NOTICE To avoid clo...

Page 163: ...s follows Procedure 1 Switch the equipment on at the main switch The operating unit switches on automatically and the system boots up NOTICE If several units are being controlled by one operating unit...

Page 164: ...may damage sensor cables or hoses which are very close to the septum to burn As a fourth possibility and to achieve a high level sterile security a silicone tube with sterile coupling can be mounted...

Page 165: ...k the syringe plunger to fill it with the necessary volume of inoculum 2 Unscrew and remove the blanking plug out of the septum col lar 3 Pierce the septum with the syringe needle and push down the sy...

Page 166: ...Before and after the sterilisation in the auto clave Always check and if necessary adjust all screw connections of the sampling system for tightness CAUTION Danger of loss of property due to using for...

Page 167: ...ten the screw connections with two fingers as necessary 3 If present remove the cap 4 If desired carry out a wiping disinfection 5 Place the Luer Lock syringe on the sample valve 6 Turn the syringe a...

Page 168: ...is led via a sterile filter Proceed as follows Procedure 1 Pull back on the syringe piston to fill it with air 2 Place the syringe on the hose on the air filter 3 Push the piston into the syringe Rem...

Page 169: ...ton of the sample syringe Ex cept for a few l all remaining liquid is removed 2 While holding the sample valve with one hand use the other hand to loosen the syringe by turning it a quarter turn count...

Page 170: ...he user Therefore Never stop fermentation by using the main switch Always stop the bioreactor and shut down the system first on the operating panel The bioreactor s can be stopped and the cultivated o...

Page 171: ...s complete and before the cul ture liquid has cooled To prevent possible sedimentation from the culture liquid the stirrer function can be switched on during har vesting However all other parameters m...

Page 172: ...hoses tubes are securely seated and that the hose tube connections can with stand the pressure 3 Discharge or transfer by generating an overpressure If a harvest tube is used the contents of the vesse...

Page 173: ...uching the Shutdown button The touch screen software is described in detail in the sepa rate operating manual 2 Switch the equipment off at the main switch NOTICE If several units are being controlled...

Page 174: ...gloves Safety shoes Maintenance work carried out inap propriately WARNING Risk of injury due to maintenance work carried out inappropriately Maintenance work carried out inappropriately may lead to s...

Page 175: ...ns increases the health risk of the operator and the risk of lower equipment functionality Therefore Strictly follow all biological safety regulations Decontaminate and sterilise every part including...

Page 176: ...d may lead to severe environmental damage Therefore Immediately take appropriate action if environ mentally hazardous substances are accidentally released into the environment 9 3 Maintenance Plan The...

Page 177: ...l the vessel top plate built in parts of the vessel top plate corrective reagent hoses and bottles and pump heads User After max 4000 operating hours approx 6 months Stirrer shaft cell cultures Exchan...

Page 178: ...ay lead to a microbial risk to the user when decontaminating and cleaning Therefore Always sterilise the appropriate components af ter each use Carry out the sterilisation process thoroughly Sterilise...

Page 179: ...ect all cable connections sensors between the equipment and the vessel 4 Cover all filters and open cable connections with a little alu minium foil 5 Disconnect the exit gas cooler from the equipment...

Page 180: ...laced at regular intervals also see the maintenance plan After max 4000 operating hours approx 6 months Auxiliary material The following components and tools are needed for replacing the ball bearings...

Page 181: ...To dismantle the used ball bearings proceed as follows Procedure 1 Remove the vessel top plate from the vessel and carefully put it top side down Avoid any stress or knocks on the stirrer shaft 2 Dis...

Page 182: ...l Bench top Bioreactor Maintenance Page 182 of 211 28 March 2018 The O ring is loose now and the stirrer shaft will also loosen itself from the bearing holder 4 Carefully pull the stirrer shaft out of...

Page 183: ...Maintenance 28 March 2018 Page 183 of 211 The whole stirrer shaft with impeller s and the two ball bear ings comes free now 5 Loosen do not remove the grub screw on the locking ring with the Allen ke...

Page 184: ...p Bioreactor Maintenance Page 184 of 211 28 March 2018 7 Remove the O ring from the stirrer shaft 8 Pull the upper ball bearing 1 off the distance sleeve 2 on the stirrer shaft 9 Pull the distance sle...

Page 185: ...are inappropriately mounted or have an incorrect axial loading Therefore Mount the ball bearings carefully and with the correct orientation Do not put pressure on the wrong side of the ball bearings S...

Page 186: ...eactor Maintenance Page 186 of 211 28 March 2018 View A Ball bearing with broad gap a between the inner and the outer ring facing upwards View B Ball bearing with narrow gap b between the inner and th...

Page 187: ...lower ball bearing with the broad gap fac ing upwards View A to the stirrer shaft NOTICE The ball bearings only support a one sided axial load They absolutely must be mounted with the correct orienta...

Page 188: ...y insert the upper ball bearing with the narrow gap facing upwards View B onto the distance sleeve NOTICE The ball bearings only support a one sided axial load They absolutely must be mounted with the...

Page 189: ...top Bioreactor Maintenance 28 March 2018 Page 189 of 211 5 Place the locking ring with the small locating ring facing to the bearing 6 Push down the locking ring and tighten the grub screw with the A...

Page 190: ...tirrer shaft in alignment with the bearing holder into the bearing holder Never insert the stirrer shaft with force and or misaligned into the bearing holder the ball bearings can easily get damaged 8...

Page 191: ...p humidity away from components which are electrically powered as excessive moisture may lead to short circuit WARNING Danger of allergies and seroconversion Contact with microbial proteins during cle...

Page 192: ...tances accidentally gain access to the environment Inform the re sponsible local authority if in doubt CAUTION Danger of scalding and burns due to contact with hot surfaces Touching the vessel holder...

Page 193: ...vessel of the main chapter Preparations for Use Furthermore these single steps are not repeatedly described General cleaning Procedure 1 Release the clamping ring and carefully take off the vessel top...

Page 194: ...vessel 12 Thoroughly rinse the vessel with distilled water G 9 6 2 Vessel Top Plate CAUTION Danger of damaging the vessel top plate or its component parts and sensors Individual component parts of the...

Page 195: ...Procedure 1 Remove the exit gas cooler from the vessel top plate 2 Put the exit gas cooler into 0 1 N NaOH for 4 hours 3 Rinse the exit gas cooler thoroughly with water 4 Put the exit gas cooler into...

Page 196: ...ll as the reagent bottles 9 6 5 Sensors CAUTION Danger of damage to the sensors The use of tools when removing sensors and care less handling of the sensors in general may lead to damages to the senso...

Page 197: ...way from components which are electrically powered as excessive moisture may lead to short circuit CAUTION Risk of damaging the operating unit The electronics of the operating unit may be dam aged if...

Page 198: ...by the user if not indicated otherwise see Tables of Inter ferences Any work on the electrical system is strictly to be carried out by qualified electricians Electrical system DANGER Danger of fatal...

Page 199: ...installed locally 2 Investigate the cause of the malfunction 3 Inform a responsible person about the malfunction trouble 4 Depending on the type of malfunction solve the problem or engage authorised q...

Page 200: ...on basic unit Qualified elec trician Interference Power indicator of the main switch is illuminated monitor of the operating unit remains dark Possible cause Remedy By Monitor of operating unit is sw...

Page 201: ...nd test operation via parameter Stirrer Operator Interference Motor control is volatile irregular or stops Possible cause Remedy By PID settings of parameter Stirrer are not correct Reset to default s...

Page 202: ...Possible cause Remedy By Thermal block has overheated automatic over temp cut out Wait for unit to cool Mechanical cut out in basic unit should re set automatically Operator Interference No cooling or...

Page 203: ...Operator Faulty pH sensor Test calibration with pH 4 and pH 7 buffer Regenerate or replace the sensor Consult the documentation of the sensor manufac turer Operator 1 This does not apply to the measu...

Page 204: ...most continuously in turn Possible cause Remedy By Incorrect PID setting in pH parame ter Check the PID settings and adjust as necessary Change the special proportional factor Prop Term or Dead band s...

Page 205: ...sor Check the calibration of the pO2 sensor Consult the documentation of the sensor manufac turer Operator Interference No pO2 control Possible cause Remedy By The pO2 parameter and or cascaded parame...

Page 206: ...Possible cause Remedy By Parameter Antifoam is not activated Activate the parameter Operator Dosing time of parameter Antifoam 0 zero Set dosing time 0 Operator Remedy No antifoam agent or medium supp...

Page 207: ...etpoint of parameter Feed 0 Set setpoint 0 Operator Reagent bottle empty Refill if necessary Operator Hose line blocked or clamped Check the hose connection between the reagent bottle and the culture...

Page 208: ...ipment or the component part which is to be repaired must be entirely decontaminated before sending to the manu facturer The operator is obliged to firstly fill in and sign a decontamina tion agreemen...

Page 209: ...he disassembly process ensure that there is sufficient space for the whole pro cedure Take care regarding sharp edged components Keep the work place tidy and clean Discarded components and tools may b...

Page 210: ...let that comes in con tact with any infectious biochemical substances e g liquids which contain bacteria or viruses 11 2 Disassembly Prior to disassembly Switch off the equipment and lock off any isol...

Page 211: ...spose of the remaining components according their material composition CAUTION Environmental damage or loss due to inappro priate disposal Electronic waste electronic components lubricants or other au...

Page 212: ......

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