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Minifors 2 - Benchtop Bioreactor

Operation

Page

180

214

07 February 2019

10.9.1 Table with Setting Values for PID Controller

Setting value

Description

P (Prop. Term)

Proportional factor: The greater the discrepancy between the set-

point value and the actual value the greater the controller output

I (Integ. Term [1/s] )

The integral factor aggregates all errors over the time. If the setpoint

is not achieved using the proportional factor, the integral factor ad-

justs the output successively until the setpoint value is achieved. An

integral factor set too high will lead to oscillation of the control loop.

D (Diff Term [s]

The differential quotient calculates the change in the actual value

over the time and counteracts this change to limit any overshoot.

Neg. Factor

The negative factor can be used to add weighting to two-sided con-

trol (+100 to -100 %) (e.g. heavy acid, light alkali). In the process 1 is

the balance and 0.5 or 2 equate to the half or double the controller

output accordingly. Example: Nitrogen influences the pO

value less

than oxygen, thus a negative factor of 2 can compensate for the re-

action of the controller.

Deadband

If a dead band is entered, no control is implemented within this value

at either side of the setpoint value (symmetrically, + / -). I.e. the con-

troller output is = 0. The dead band is used for pH control.

I Limit (Integ. Limit [%])

The integral influence is used to ensure that the integral factor can-

not increase over an indefinite period. This limits erroneous accumu-

lation. The integral influence is set between 0 and 100 % of the con-

troller output.

Eval Time [s]

The evaluation time determines the intervals in seconds at which the

PID value is recalculated. The controller speed is defined this way. A

scanning time of 10 seconds is a good average value.

10.9.2 Useful Information for Changing PID Controller Settings

To adjust the PID controller settings, proceed as follows:

Procedure

For readjustment of a PID controller, start with the setting for

the proportional factor. Select a proportional band width as

large as possible.

Reset the integral factor and the differential quotient to zero.

Increase the proportional factor until the controller causes the

actual value to oscillate.

Measure the oscillation duration, e.g. with the bioprocess plat-

form software eve® from the manufacturer.

Halve the proportional factor and vary the integral factor be-

tween the reciprocal value of the doubled and quadrupled os-

cillation duration.

Содержание Minifors 2

Страница 1: ...Operating Manual 2019 02 07 Minifors 2 Benchtop Bioreactor Dok ID 75623 V 03 00 Original...

Страница 2: ...SA 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 8350 rue Bombardi...

Страница 3: ...2 4 Responsibility of the Provider 15 2 5 General Hazards 15 2 5 1 Electrical Current 16 2 5 2 Unauthorised Spare Parts and Accessories 16 2 6 Particular Hazards 16 2 6 1 Hot Surfaces 17 2 6 2 Danger...

Страница 4: ...System 33 3 5 Stirrer 34 3 6 Gassing System 35 3 6 1 Gas Entry 36 3 6 2 Exit Gas 36 3 7 pH Control 36 3 7 1 Measurement System 36 3 8 pO2 Control 37 3 8 1 Measurement System 38 3 9 Antifoam Control 39...

Страница 5: ...5 20 Starter Kit 62 5 21 Service Sets 62 5 22 Auxiliary Supplies 62 6 Transport and Storage 63 6 1 Transport 63 6 2 Storage 64 7 Installation and Initial Operation 65 7 1 General Location Requirements...

Страница 6: ...Mounting a Sensor into a 12 mm Port 86 8 1 18 Mounting Sensors with Electrode Holder 87 8 1 19 Mounting the Antifoam Sensor 89 8 1 20 Preparing the Super Safe Sampler 91 8 1 21 Mounting the Sparger Ho...

Страница 7: ...ivation 116 10 Operation 118 10 1 Screen Areas Menu Navigation and Control Elements 118 10 1 1 Main Screen 120 10 1 2 EDIT VIEW 121 10 1 3 START BATCH INOCULATE STOP BATCH 122 10 1 4 SAMPLE NOW 123 10...

Страница 8: ...TY Automatically Filling Emptying Pump Hoses 158 10 8 Calibration 159 10 8 1 Calibrating the pH Sensor General Information 159 10 8 2 Calibrating the pH Sensor Procedure 160 10 8 3 pH Sensor Product C...

Страница 9: ...er 191 11 8 Cleaning the Exit Gas Cooler 191 11 9 Cleaning the Basic Unit and Operating Panel 192 11 10 Maintenance Plan 192 11 11 Decalcifying the Equipment 193 12 Interferences 195 12 1 Interference...

Страница 10: ...14 4 4 Gas Air O2 or N2 208 14 5 Specifications 208 14 5 1 Operating Panel 208 14 5 2 Culture Vessels 208 14 5 3 Stirrer 209 14 5 4 Temperature 210 14 5 5 Gassing 211 14 5 6 pH 211 14 5 7 pO2 212 14...

Страница 11: ...roughly and fully un derstand its contents before beginning any work Adhering to all the safety and operating instructions in this manual is essential to ensure that work is carried out safely The sco...

Страница 12: ...at may result in significant damage to property if not avoided INFORMATION Texts located below a grey bar bearing the notice INFOR MATION provide useful tips and recommendations for ensuring efficient...

Страница 13: ...at your disposal for technical advice and specialist enquiries For contact information see page 2 Due to their familiarity with the potential applications of the equip ment the Customer Service team i...

Страница 14: ...wareness of the associated risks 2 1 Intended Use Incorrect Use and Misuse The bench top bioreactor Minifors 2 from INFORS HT is de signed especially for research and development and for the cultivati...

Страница 15: ...ecessary infrastructure available These persons may also be included in the group of people known as users though this is not always the case Irrespective of whether a provider is a member of the comp...

Страница 16: ...have been trained for working in a biotech nology laboratory can be considered for the role of operator These include Process technicians in the fields of biotechnology and chemis try Biotechnologists...

Страница 17: ...rements relating to occupational health and safety in a biotechnology laboratory In particular The provider is responsible for ensuring that the work and en vironmental regulations applicable in a bio...

Страница 18: ...cuit 2 5 2 Unauthorised Spare Parts and Accessories Incorrect or imitated spare parts and accessories as well as spare parts or accessories that have not been authorised by the manu facturer represent...

Страница 19: ...ces In order to prevent high emissions of dangerous gases the follow ing measures must be taken The gas connections on the equipment must be checked be fore any cultivation processes using dangerous g...

Страница 20: ...nce the equipment is used deliberately for such applications it is the responsibility of the users to ensure that they have sufficient protection 2 6 6 Overpressure or Vacuum Glass vessels may break o...

Страница 21: ...econtaminated before sending to the manufacturer The provider is therefore required to completely and truthfully fill out a declaration of decontamination and have it signed by the person responsible...

Страница 22: ...s 2 Thermal block and adapter 3 Connections for sparger and exit gas cooler 4 Operating panel 5 LED signal strip 6 Main switch 7 Connections for sensors 8 Hooks for vessel holder All of the measuremen...

Страница 23: ...p green as soon as it is switched on 3 1 2 LED Strip The LED strip is located on the front of the basic unit When the LED strip Lights up green as soon as the equipment is switched on The equipment is...

Страница 24: ...e pumps This is numbered 1 to 4 from bottom to top and labelled to indicate the standard factory settings Pump 1 Acid digital Alternative setting FEED analogue Pump 2 Base digital Alternative setting...

Страница 25: ...6 Water Connections The water connections are located on the rear of the basic unit at the bottom right They are marked with the following symbols H2O IN water inlet H2O OUT water outlet 3 1 7 Gas Co...

Страница 26: ...located on the rear of the basic unit at the bottom left SERVICE 9 pin RS232 for connecting a diagnostic com puter for maintenance BALANCE 9 pin RS232 for connecting a balance LAN port for connecting...

Страница 27: ...and the connecting cables for the pH pO2 and antifoam sensors are always present The matching sensors for pH pO2 and anti foam are included in the standard package 1 pO2 2 Temperature Pt100 3 Antifoam...

Страница 28: ...cooler are located on the front of the basic unit at the bottom left They are marked with the corresponding symbols 1 Exit gas cooler water outlet 2 Exit gas cooler water inlet The water supply and re...

Страница 29: ...ve can be fixed in the required position using a lock nut 3 2 Operating Panel The operating panel on the top right of the basic unit has a 7 TFT colour touch screen On the right hand side of the panel...

Страница 30: ...6 Reagent bottle holder 7 Vessel holder 8 Top plate The illustration shows a culture vessel with a total volume of 1 5 L and a nominal width of 90 mm There are three vessel sizes availa ble each with...

Страница 31: ...O ring 5 Damping ring spacer ring 6 Flange The top plate is attached to the vessel using four knurled screws and a flange The knurled screws also hold the vessel in place in the vessel holder An O ri...

Страница 32: ...etc The number of ports in the top plate and its configuration de pends on the diameter nominal inner diameter of the culture vessel 3 3 3 Vessel Top Plate Nominal Width 90 1 12 mm Pg13 5 pH sensor 2...

Страница 33: ...12 mm Pg13 5 Exit gas cooler 3 12 mm Pg13 5 Additional sensor 4 7 5 mm Addition port adaptors 4x 5 10 mm Sparger 6 12 mm Pg13 5 pO2 sensor 7 12 mm Pg13 5 Additional sensor 8 10 mm Temperature sensor P...

Страница 34: ...Additional sensor 3 7 5 mm Addition port adaptors 4x 4 10 mm Sparger 5 10 mm Dip tube for sampling 6 12 mm Pg13 5 pH sensor 7 12 mm Pg13 5 pO2 sensor 8 10 mm Temperature sensor Pt100 9 Antifoam sensor...

Страница 35: ...thermal block The temperature in the culture vessel is measured using a plati num resistor temperature sensor Pt100 The temperature is transmitted from the thermal block to the adapter and from the a...

Страница 36: ...rrer The stirrer shaft is driven from above and turns anti clockwise left when viewing vessel from above 1 Drive hub 2 Stirrer shaft 3 Mechanical seal The stirrer shaft is sealed using a mechanical se...

Страница 37: ...els with nominal widths 115 and 145 The motor is connected by pushing it onto the drive hub on the top plate 3 6 Gassing System The following gases can be used Air Oxygen O2 or nitrogen N2 The basic u...

Страница 38: ...exit gas filter from becoming clogged with moisture At the same time it also prevents liquid loss in the culture medium INFORMATION If heavy foaming is expected a bottle of antifoam agent can be inst...

Страница 39: ...Operation chapter Cali brating the pH Sensor INFORMATION If the pH sensor has already been calibrated before connection to the system the bioreactor will use this data and calibration on the operatin...

Страница 40: ...the following applies Unlike measurements such as pH which are calibrated to absolute measurement values the oxygen measurement is always calibrated to a relative refer ence point For this purpose th...

Страница 41: ...ent bottle that is connected to the antifoam sensor and the antifoam pump via a hose The sensor also acts as a dosing needle When the sensor comes in contact with foam the antifoam pump is activated a...

Страница 42: ...at is integrated into the bioreactor basic unit Type ASD12 N with OPL05 optical path length for higher cell densities Manufacturer Optek Measures the absorption in the 0 4 CU range The ASD12 N sensors...

Страница 43: ...contact with the media are made of electrolytically polished steel Main components 1 LED light source 2 Sapphire window 3 Optical path length OPL 4 Daylight filter 5 Silicon photodiode detector A defi...

Страница 44: ...an O ring fit an O ring if necessary Mount the sensor by hand do not use any tools If the mounting depth of the sensor is adjustable mounting with electrode holder make sure the mounting depth is set...

Страница 45: ...suring system automatically switches off if the temper ature of the sensor in the medium exceeds 50 C during opera tion thermal shutdown Once the medium has cooled down measurement automatically conti...

Страница 46: ...0 25 INFORMATION Both sensor types are only suitable for use in aerobic bopro cesses For details on the safety technical data usage and maintenance requirements for the gas sensors see the separate do...

Страница 47: ...ow on the gas sensor s flow adapter and fasten in place with the clamp 3 Push the open end of the hose onto the exit gas filter on the exit gas cooler INFORMATION Do NOT use a clamp here as the hose m...

Страница 48: ...t 1 1 1 Addition port adaptor for 7 5 mm port 4 4 4 Clamping adapter for 10 mm port 3 3 3 Antifoam sensor for 10 mm port 1 1 1 Blanking plug for 12 mm Pg13 5 port 4 6 7 Blanking plug for 10 mm port 2...

Страница 49: ...rectly into the medium via a ring sparger 6 mm The sparger is mounted in a 10 mm port in the vessel top plate using a clamping adaptor and connected to the gassing sys tem on the basic unit via a sili...

Страница 50: ...ing Adaptors and Fastening Screws section Blanking plug 12 mm Must be fitted with an O ring before being mounted in the 12 mm Pg13 5 port Mounted using a thread 5 5 Clamping Adapters and Fastening Scr...

Страница 51: ...ping adapter Fastening screw M5 The fastening screws are used to hold components in place in the 10 mm ports in the vessel top plate 5 6 Electrode Holder Electrode holders are used for mounting sensor...

Страница 52: ...diameter 2 mm Hose connection outside diame ter 4 mm Installation depth 17 mm Addition port adapters protrude as far as the head space of the vessel and have very sharp ends with slanted points Each c...

Страница 53: ...culture vessel after autoclaving Using a dip tube prevents foaming For adding inoculum For sampling The aseptic Super Safe Sampler system can be used for sampling For harvesting For siphoning off med...

Страница 54: ...perature Sensor Pt100 The pocket is a pipe with a sealed bottom end and is used to in sert the temperature sensor Pocket 10 mm Fitted with fixed O ring A fastening screw is used to fasten it in the 10...

Страница 55: ...The hose connections and the exit gas filter are secured with hose clamps The hose clamp securing the exit gas filter is equipped with a screw that can be used to loosen or tight it manually 1 Pressur...

Страница 56: ...addition port adapter in the culture vessel and to a pump head 1 Filter 2 Silicone hose 2 x 6 mm 3 Cable tie INFORMATION 250 mL reagent bottles are supplied as standard in the unit package These fit...

Страница 57: ...s connected via silicone hose with a dip tube Valve assembly 1 Sterile filter 2 Check valve 3 Luer activated sample valve 4 T piece 5 Hose The valve assembly consists of a T piece two check valves a L...

Страница 58: ...line this sampling system can save culture volume which is particularly important with small vessels and or frequent sampling The dead volume of the culture remaining in the group of valves after flu...

Страница 59: ...inge disinfect the sample valve Fort this spray a commercially available disinfectant onto the valve After spraying and after each sampling close the the sample valve with a sterile Luer Lock cap Dead...

Страница 60: ...are placed in the two holders and the mount ing plate with the pump heads is simply pushed onto the pump holder The culture vessel can this be transported and autoclaved as a sin gle unit together wi...

Страница 61: ...dry at all times and should thus ideally be replaced after each use 37 mm marked red Application Inlet air sparger 1 5 lit culture vessels Retention rate 0 2 m 50 mm Type ACro50 TF no label Usage Inl...

Страница 62: ...n sparger for 3 0 and 6 0 L TV culture vessels Silicone hose 5 x 8 mm Gassing sparger Pressure hose trans parent 4 x 8 mm Water supply and return exit gas cooler Silicone hose transpar ent 2 x 6 mm Re...

Страница 63: ...ring 120 x 105 Damping ring between glass vessel and vessel holder NW90 PTFE ring 145 x 130 Damping ring between glass vessel and vessel holder NW115 PTFE ring 175 x 160 Damping ring between glass ves...

Страница 64: ...ntents list is included in each starter kit 5 21 Service Sets Service sets with O rings gaskets sterile filters hoses etc to fit each vessel size are available separately A detailed contents list is i...

Страница 65: ...e The following points must be observed when transporting the equipment internally relocation Always work in pairs and use suitable auxiliary equipment when transporting the equipment The entire equip...

Страница 66: ...d its components clean dry and pro tected against dust dirt and liquids Store the equipment and its components in a cool place with low air humidity but protected against frost Storage temperature 5 C...

Страница 67: ...nges specified in the chapters Technical Data Connection Values and Technical Data Operating Conditions must be observed The equipment must only be installed inside a laboratory or a laboratory like e...

Страница 68: ...wer supply 7 3 2 Water Supply and Return Connection conditions The in house water supply to the unit as well as the drainage of the water must meet the following requirements Very soft or soft water q...

Страница 69: ...bar Gas es is are dry clean and free of oil and dust Recommended compressed air quality as per DIN ISO 8573 1 Class 1 2 3 4 ATTENTION The use of impure gases can lead to blockage of the sterile filter...

Страница 70: ...he laboratory laboratory like facility is equipped with a sufficient ventilation system de pending on the application 7 4 Connecting the Motor Cable The motor is controlled directly via the basic unit...

Страница 71: ...To avoid calcium deposits demineralised water is recommended for filling the vessel The following description of the test run does not detail handling of individual components e g exit gas cooler sti...

Страница 72: ...to this end follow the symbols on the basic unit water inlet on bottom of exit gas cooler water outlet at top of exit gas cooler 7 Close all remaining open ports with blanking plugs 8 Hang the culture...

Страница 73: ...t of the procedure allow the Batch to run with the tem perature switched on 7 5 3 Stirring Batch process is running with temperature switched on To test the stirrer proceed as follows Procedure 1 On t...

Страница 74: ...m airflow depends on the size of the culture vessel and the correct setting in the Vessel Type menu 3 Ensure that all other gas parameters Gas2Flow TotalFlow GasMix are switched off If the gassing is...

Страница 75: ...Bioreactor Installation and Initial Operation 07 February 2019 Page 73 of 214 When the motor has cooled down 5 Uncouple the motor from the vessel and place it on a clean and dry work surface 6 Empty...

Страница 76: ...sel if necessary Preparing sensors and other accessories 8 1 Preparing and Autoclaving the Culture Vessel All accessories required for later cultivation must be prepared and mounted accordingly and au...

Страница 77: ...ecessary reposition or replace If component parts are fitted into other component parts clamping adap tor there must also be an O ring between them INFORMATION Septum collars are sealed with a septum...

Страница 78: ...late is described here This means that the vessel top plate is still removed During mounting ensure that the sparger or the dip tube does not come into contact with other component parts stirrer The s...

Страница 79: ...ten the slotted head screw 8 1 4 Inserting the Vessel into the Vessel Holder To insert the glass vessel into the vessel holder proceed as fol lows Procedure 1 Place the flange onto the ring of the ves...

Страница 80: ...Benchtop Bioreactor Before Cultivation Page 78 of 214 07 February 2019 3 Insert the vessel carefully 8 1 5 Inserting the Baffles Proceed as follows Procedure 1 Insert the baffles carefully into the gl...

Страница 81: ...oss of volume and thus to increased salt concentration in the medium If nec essary top up with sterile water INFORMATION Development of steam is not possible when autoclaving an empty and dry culture...

Страница 82: ...hich can result in failure of the equipment The screws may not be tightened with a tool under any circumstances This applies to all screw connections where the instructions specify that they must be t...

Страница 83: ...nsert the O ring and blanking plug into all unused ports 2 Tighten by hand 3 Use the hexagon socket spanner to make it hand tight 8 1 9 Mounting Addition Port Adapters Proceed as follows Procedure 1 I...

Страница 84: ...the chapter Mounting Addition Port Adapters 8 1 11 Mounting the Pocket for Temperature Sensor Pt100 Proceed as follows Procedure 1 Insert the pocket with the fixed O ring into the 10 mm port 2 Fix it...

Страница 85: ...ep tum collar and screw it tight by hand If necessary use the hexagon socket spanner to make it hand tight 8 1 13 Preparing the Dip Tube Addition Port Adapter for Inoculation If later inoculation is t...

Страница 86: ...her com ponent parts is impaired as little as possible 4 Check to ensure that the exit gas filter is fitted securely 5 Cap the exit gas filter loosely with a little aluminium foil INFORMATION A humidi...

Страница 87: ...he operating panel before mount ing and autoclaving pO2 sensor Mount the pO2 sensor in such a way that it has good access to the flow and there is no risk of bubbles collecting Calibra tion is carried...

Страница 88: ...ng panel is switched on automatically and the sys tem is started 3 Calibrate the pH sensor in accordance with the detailed de scription in the main chapter Operation chapter Calibrating the pH Sensor...

Страница 89: ...of a sensor in a 12 mm Pg13 5 port for culture vessels with a nominal width of 115 an electrode holder must be used To do so proceed as follows Procedure 1 On the electrode holder lightly loosen the g...

Страница 90: ...ad pointing in the downward direction 5 Fit the fork of the guide bar into the groove of the hollow screw 6 Push the hollow screw and the guide bar together upwards and insert the guide bar into the h...

Страница 91: ...nting The antifoam sensor is equipped with transparent insulation that must be intact as otherwise a continuous signal Foam liquid detected may be generated The sensor head must not touch the clamping...

Страница 92: ...lotted head screw at the clamping adaptor 5 Set the desired mounting depth of the sensor carefully 6 Tighten the slotted head screw carefully ATTENTION If the sensor is fixed too tightly in the clampi...

Страница 93: ...l purposes of comprehen sion In order to prepare the Super Safe Sampler sampling system for autoclaving proceed as follows Procedure 1 Attach the hose of the valve group on the dip tube 2 Secure the h...

Страница 94: ...21 Mounting the Sparger Hose and the Inlet Air Filter The sparger must be equipped with the hose and inlet air filter be fore autoclaving To do so proceed as follows Procedure 1 Cut a short piece of...

Страница 95: ...2 Preparing the Reagent Bottles Pumps and Hoses 250 mL reagent bottles are supplied as standard in the equipment package These fit in the reagent bottle holder that is built into the vessel holder Bef...

Страница 96: ...cone hoses must be selected to ensure that the hose connections between the reagent bottles pumps and culture vessel do not have any tensions or kinks 2 Thoroughly rinse the silicone hoses with distil...

Страница 97: ...s not touch the bottom of the bot tle otherwise the hose may get sucked against the bot tom and no longer be able to pump liquid b the end of the hose is cut diagonally In this case the hose end can t...

Страница 98: ...el 7 Ensure that each reagent bottle is connected with the appropriate pump according to its contents Base to base pump etc filters are clean and dry short hose line is open 8 Cap the filter loosely w...

Страница 99: ...process started To this end the diameter of the hose used must be selected For details on the pumps and the setting options see the main chapter Operation the PUMPS parameter group chapter and the as...

Страница 100: ...nto the opening of the drive hub 8 1 27 Checklist Before Autoclaving Check and ensure the following items before autoclaving Culture vessel All necessary O rings are fitted All unused ports are closed...

Страница 101: ...to prevent them from slipping Hoses on the reagent bottles for sampling and the gassing system sparger are clamped off with hose clamps The exit gas hose is NOT clamped off The hoses are undamaged th...

Страница 102: ...vessel to from the autoclave note the following Always transport the culture vessel in the vessel holder Always transport the culture vessel to from the autoclave in pairs and use suitable auxiliary e...

Страница 103: ...in Place and Fit the Pump Heads Proceed as follows Procedure 1 Hang the vessel holder into place on the two hooks on the thermal block adapter 2 Pull off the mounting plate with the pump heads from th...

Страница 104: ...l if possible For details on filling see the main chapter Operation chapter Parameter Group PUMPS 8 2 3 Connecting the Gassing To connect the sparger to the gassing proceed as follows Procedure 1 Remo...

Страница 105: ...unit onto the upper connection nozzle on the exit gas cooler INFORMATION The exit gas cooler only works when the temperature control system is switched on Temperature ON parameter 8 2 5 Coupling the...

Страница 106: ...e To do so proceed as follows Procedure 1 Sterilise the medium separately 2 If necessary pump off any water that remains in the culture vessel 3 Establish a sterile hose connection between the culture...

Страница 107: ...is not in direct contact with the medium Procedure 1 Insert the sensor into the pocket in the vessel top plate as far as it will go 8 2 8 Connecting the Antifoam Sensor To connect the antifoam sensor...

Страница 108: ...r To connect the pH sensor proceed as follows Procedure 1 Remove the red protective cap from the sensor cable 2 Place the connector of the sensor cable onto the sensor head and screw into place Ensure...

Страница 109: ...O2 sen sor is calibrated either before the vessel is filled with medium or afterwards in the prepared medium For more details on the calibration refer to main chapter Opera tion chapter Calibrating th...

Страница 110: ...bottles are present pump heads are mounted and the reagent hoses are filled Depending on the user specifications the pO2 sensor is already calibrated 9 1 Preparing the Medium Before the first samplin...

Страница 111: ...the operating panel the sampling can be logged in the electronic logbook and assigned a sample ID For more details see main chapter Operation The method of sampling can vary due to the different analy...

Страница 112: ...erile syringe and sterile closing caps For details see the main chapter Accessories chapter Sampling System Super Safe Sampler section Aseptic Sampling Proceed as follows Procedure 1 Check that all sc...

Страница 113: ...ng hose can be filled with sterile air af ter taking a sample INFORMATION Only use a clean and dry syringe to avoid blocking the sterile fil ter This syringe can be reused as often as desired since ai...

Страница 114: ...ample 9 3 Inoculation Check and ensure the following items before inoculation Medium has been filled Heat labile separately sterilised substances are present The reagent bottles are connected with the...

Страница 115: ...rticularly suitable for all vessel sizes of the equipment 9 3 1 Inoculation with a Syringe Proceed as follows for the inoculation Procedure 1 Fill the syringe with the required amount of inoculum 2 Un...

Страница 116: ...down via a sterile hose connection To do so proceed as follows Procedure 1 Make a sterile connection between the hose at the dip tube for harvest and the new vessel 2 Connect the hose to one of the pu...

Страница 117: ...o the local regulations 9 6 Emptying the Reagent Hoses Before autoclaving the culture vessel with accessories all reagent hoses must be completely emptied using the corresponding pump This can either...

Страница 118: ...r the user specific specifications and then clean them 9 8 Autoclaving the Culture Vessel After Cultivation After emptying the culture vessel and before cleaning the culture vessel must be autoclaved...

Страница 119: ...all filters with aluminium foil ATTENTION Do not cover the pH and pO2 sensors with aluminium foil 5 Fit the cone plug into the opening of the drive hub ATTENTION Risk of loss of property du penetrati...

Страница 120: ...displays 3 Main screen 4 Display of the Batch time since inoculation and possible alarms 5 Buttons for the selection of the parameter dis play and time stamp for sampling 6 Buttons with changing func...

Страница 121: ...nnection to SCADA software Display for an active wireless connection Alarm display If alarms occur equipment alarm or parameter alarm they are signalled by a red exclamation mark highlighted in white...

Страница 122: ...VESSEL TYPE menu for setting the vessel size Depending on the menu selected the CANCEL and OK but tons or only the OK button are available in the menu footer OK saves the changes and closes the menu...

Страница 123: ...ed to show or hide parts of the menu and display The figure to the left shows the example of the menu with parame ter options which becomes visible after pressing the arrow button on the right hand ed...

Страница 124: ...urrent parameter settings are simultaneously logged in a log file and re cording of the actual values begins INFORMATION Log files can be exported on a USB stick The button now changes function to INO...

Страница 125: ...removed from the culture vessel by hand this can be signalled to the bioreactor by pressing SAMPLE NOW This logs the sampling and is visible in the log files for the batch For details see the USB Dat...

Страница 126: ...h six are availa ble for the operator VESSEL TYPE Selection of the culture vessel used APPEARANCE Display settings including language and time NETWORK SETTINGS Network configuration eve COMMUNICATION...

Страница 127: ...e available in the menu footer 10 2 1 VESSEL TYPE Selecting a Culture Vessel The culture vessel used is set in the VESSEL TYPE menu There are three culture vessel sizes ATTENTION With the selection of...

Страница 128: ...display language The desired display language can be selected using the pull down menu The languages in the pull down menu are always displayed in English INFORMATION Additional languages can be down...

Страница 129: ...ay of the info buttons for the on screen help for the vari ous parameters is switched on YES or off NO using the switch If the display is switched on the info buttons also appear in the main screen Af...

Страница 130: ...e date and the time of the bioreactor cannot be set manually SET DATE AND TIME SET DATE AND TIME Manually enter the date and time Can only be done provided AC CEPT DATE AND TIME FROM OPC is not switch...

Страница 131: ...igura tion with the DHCP protocol Please consult your network adminis trator IP ADDRESS Displays the allocated IP address during automatic configuration Auto DHCP or can be used to enter the IP addres...

Страница 132: ...ss IP configuration under NETWORK SETTINGS This infor mation is required for configuration of the connection in eve equipment manufacturer s bioprocess platform software SERVER ACCESS Determine whethe...

Страница 133: ...USB Stick In the USB menu a USB stick connected with the equipment s USB port can be used to import or export data EXPORT DATA TO USB Opens the menu for data export The selection menu in the left han...

Страница 134: ...CSV format In combination with the initial state at batch start parameters json the current configuration can be determined at any time The columns of the CSV file are DateTime Absolute date and time...

Страница 135: ...data import from a USB stick for the data im port of the parameter configuration This also contains the cas cades and the PID settings UPDATE FIRMWARE Carries out an update of the controller firmware...

Страница 136: ...ation In the SYSTEM INFO menu the currently installed version of the firmware and the operating hours since start up are displayed 10 3 Parameter Parameter Groups On the main screen up to eight parame...

Страница 137: ...d Turbidity if avail able EXIT GAS Contains the Exit GasO2 and Exit GasCO2 param eters provided the exit gas analysis option is available PUMPS Contains the Pump1 to Pump4 parameters and also offers t...

Страница 138: ...ters Operation is described in the Calibration section Editing opens the editor menu with the various settings for the selected pa rameter Not all parameters have an editor menu Amongst other options...

Страница 139: ...tarted using START BATCH and the correspond ing parameter has been activated using ON OFF After pressing the input field in the SETPOINT column of the de sired parameter the key pad appears for typing...

Страница 140: ...arms If a parameter is activated and the Batch inoculated parameter alarms are generated after a predefined waiting time if there are unexpected deviations from the actual values and setpoints Alarm g...

Страница 141: ...A red exclamation mark highlighted in white on a red back ground appears in the footer Pressing the symbol or swiping upwards opens the Equipment Alarm menu For details see the Alarms Equipment Alarm...

Страница 142: ...below the prescribed setpoint the Gasmix is in creased by the controller until the desired setpoint is reached for the pO2 The cascades can be configured using the editor menu of the pa rameter The p...

Страница 143: ...Temperature Measures and controls the temperature in the culture vessel 10 4 2 Stirrer Measures and controls the speed of the stirrer Rotation speed de pends on factors such as the size of the motor v...

Страница 144: ...ttings for the cascade are carried out in the editor menu of the parameter At the CASCADE menu item the pull down menu is used to call up the list of pre defined cascades for pH control The following...

Страница 145: ...For this purpose the calibration is set to 100 relative oxygen saturation usually with air at max stirring speed and maximum gas flow rate The actual concentration of dissolved oxygen in mmol L 1 may...

Страница 146: ...ing GasMix Serial cascades Stirrer TotalFlow pO2 is first controlled by Stirrer and after reaching its maximum it is controlled by TotalFlow Stirrer Gasmix pO2 is first controlled by Stirrer and after...

Страница 147: ...ssociated subchapters If necessary the value ranges used for the cascaded parameter s can be adjusted here In the example below the cascaded parameter Stirrer is selected for this purpose in the visua...

Страница 148: ...mposition or the gas composition to be kept constant in the event of a changing volume flow The measurement value is displayed in L min 1 The sum of the volume flows TotalFlow is often used in a casca...

Страница 149: ...ion entry is confirmed using OK The gas composition Gasmix is often used in a cascade for pO2 control Cascades for pO2 control can be configured in the editor menu of the pO2 parameters 10 4 7 Foam In...

Страница 150: ...on of anti foaming agent to reduce foam before more antifoaming agent is added ALARM TIME Time in seconds after which a parameter alarm is triggered if foam is still detected despite the addition of a...

Страница 151: ...ment 10 5 2 Balance Optional Measures a weight e g a bottle with feed solution Can be coupled with Pump4 feed to carry out gravimetric feeding See the Pump4 feed solution section for details The balan...

Страница 152: ...low can only be controlled individually when TotalFlow and Gasmix are deactivated 10 5 4 Gas2Flow Measures and controls the flow rate of the optional second gas into the culture vessel using a mass fl...

Страница 153: ...al exit gas analysis Details on technical data usage and maintenance requirements for the gas sensors can be found in separate documentation provided by the manufacturer ATTENTION Risk of damage to th...

Страница 154: ...parameter group the delivery rate of the pumps can be set or monitored and the function mode of the pumps can be configured In addition the pump hoses can be manually filled or emptied by pressing an...

Страница 155: ...e Foam parameter Pump 4 FEED Addition of feed solution analogue with vari able speed controlled by the user The figure below shows the pumps with the factory configuration In digital operation pumping...

Страница 156: ...tor menu of Pump 1 as an ex ample TUBE TYPE Select the pump hose used The following pump hoses are available 0 5 mm 1 0 mm stand ard or 2 5 mm On the basis of the selected hose diameter the pumped vol...

Страница 157: ...stimated on the basis of the hose diameter selected under TUBE TYPE If a balance Balance is connected and linked with Pump4 g measured pumped weight is also available at Pump4 RESET COUNT Here the tot...

Страница 158: ...ntries in the editor menu of the pH parameter 10 7 4 Pump3 Antifoam Level or Additional Feed Solution Pump3 can be configured for the AntiFoam function mode factory setting Level or Feed AntiFoam The...

Страница 159: ...alance Feed Feed Pump operation is analogue and is used for the addi tion of feed solution Balance Feed Pump operation is analogue and is used for the addition of feed solution The delivery rate is co...

Страница 160: ...he sub menu for automatic filling and emptying of the pump hoses is opened For each pump an individual filling duration FILLING DURATION as well as an individual emptying duration EMPTYING DURA TION c...

Страница 161: ...required or a 1 point calibration and a zero point adjustment is sufficient The various calibrations are described in the following sections 10 8 1 Calibrating the pH Sensor General Information In gen...

Страница 162: ...o calibrate the pH sensor at the operating panel Procedure 1 Connect the sensor cable For details see the Before Cultiva tion section and the Connecting the pH Sensor sub section 2 Carefully remove th...

Страница 163: ...produced by the firmware of the sensor manufacturer that is integrated in the sensor 4 Select 2 point calibration The menu display changes and displays the following Left hand side First Calibration...

Страница 164: ...of the desired reference value INFORMATION The pH sensors are calibrated with the following standard set tings ex works Buffer pH 4 calibration point 1 buffer pH 7 cali bration point 2 at room tempera...

Страница 165: ...ted the cur rent pH measured value appears and CALIBRATE POINT 1 is activated i e the button turns orange 7 Press CALIBRATE POINT 1 to begin calibration CONFIRM NOW creates a visual representation of...

Страница 166: ...en the desired reference value has been selected the cur rent pH measured value appears and CALIBRATE POINT 2 is activated i e the button turns orange 11 Press CALIBRATE POINT 2 to begin calibration C...

Страница 167: ...only effective if the externally measured and entered pH value does not deviate from the original pH value by more than 2 pH units Proceed as follows for a product calibration Procedure 1 Call up the...

Страница 168: ...firm Sample was taken at Display of date and time of the sampling 2 Measure the pH of the sample and enter the value Measure the pH of the sample and enter the value 3 Start the calibration Start the...

Страница 169: ...tion OR b Confirm the sampling generate a time stamp leave the calibration menu and carry out the product calibration with an external measured value at a later time Variant a Procedure 1 Press CONFIR...

Страница 170: ...bora tory measurement of the pH value for the sample at a later time of your choosing In the calibration menu Sample Taken is displayed under PRODUCT CALIBRATION to show that sampling was carried out...

Страница 171: ...er the following conditions in medium at operating temperature at the maximum expected stirrer speed at the maximum expected gas flow rate for air or the oxygen containing gas ses provided for the cul...

Страница 172: ...connec tion In the process leave the gas supply closed INFORMATION If necessary enter setpoints for temperature and pH activate parameters and press START BATCH and wait until the desired operating te...

Страница 173: ...bration 1 POINT CALIBRATION Select 1 point calibration 2 POINT CALIBRATION Select 2 point calibration SHOW SENSOR STATUS Shows data and values produced by the firmware of the sensor manufacturer integ...

Страница 174: ...the reference value of the first calibration point 2 Optionally set setpoints for XX pO2 If necessary enter the setpoint for XX pO2 corresponding gassing and stirrer are activated by this 3 Evaluate...

Страница 175: ...play CALIBRATE POINT1 Start the calibration procedure for the 1st calibration point CONFIRM NOW Confirm the calibration and continue with the 2nd calibration point 4 Slowly open the nitrogen supply 5...

Страница 176: ...n has been displaced from the medium i e wait until the measured value display via CALIBRATE POINT 1 is stable 9 Press CALIBRATE POINT 1 to begin calibration Gassing and the stirrer are stopped CONFIR...

Страница 177: ...not calibrated one after the other in 1 point calibration mode is activated i e the but ton turns orange INFORMATION This facilitates a calibration of the sensor outside of the medium i e without acti...

Страница 178: ...Turbidity Sensor General Information Optek turbidity sensors optional are pre calibrated in the factory Inserts are available for reference measurement Due to the different light absorption of differ...

Страница 179: ...il measurement is stable Wait until the measured value is stable 2 Perform zero point calibration Carry out zero point calibra tion 3 Wait until the measured value is stable display via CALI BRATE 4 P...

Страница 180: ...actor is 0 05 D differential quotient derivative of the error set in seconds mostly to 0 Be aware of the following relating to the individual factors Proportional factor The change of the proportional...

Страница 181: ...as it exceeds the time minimum for which the control is required This causes fluctu ations in the control circuit Example of calculation of the integral factor The cycle duration of system oscillatio...

Страница 182: ...band If a dead band is entered no control is implemented within this value at either side of the setpoint value symmetrically I e the con troller output is 0 The dead band is used for pH control I Lim...

Страница 183: ...menu of the corresponding parameter and therefore described there 10 10 Alarms Equipment Alarm Menu There are two types of alarm that appear in the Equipment Alarm menu Parameter alarms Display of de...

Страница 184: ...quip ment Alarm menu DESCRIPTION Display of the type of alarm STATE Status display of the alarm open or resolved Open alarms are displayed in red and with the word Open Resolved alarms are displayed i...

Страница 185: ...washing agent for industry and lab use Cleaning agent for dena turation of proteins e g exit gas cooler 0 1 N NaOH Cleaning agent for smaller component parts e g exit gas cooler dip tube Ultrasonic ba...

Страница 186: ...e vessel top plate ports and place them to the side for separate cleaning according to the manu facturer guidelines 2 Completely fill the culture vessel with 0 1 N NaOH 3 Fit the top plate on the vess...

Страница 187: ...essel top plate port by hand Ensure that the O ring does not get lost 2 Gently release the hose clamp with the hand wheel pull off the exit gas filter and dispose of it 3 Remove the pressure hose piec...

Страница 188: ...avoid damage never dismantle the pump heads Always re place a damaged pump head along with the pump hose and vice versa Proceed as follows Procedure 1 Remove cable ties e g with a side cutter so that...

Страница 189: ...cedure 1 Loosen the blanking plug with a hexagon socket spanner in the septum collar and remove it by hand Ensure that the O ring does not get lost 2 Unscrew the septum collar out of the port by hand...

Страница 190: ...remove the stirrer shaft 5 Check the glass vessel for damage cracks fissures scratches and replace if necessary 11 3 8 Removing the Sparger and the Dip Tube s Straight spargers and dip tubes can be re...

Страница 191: ...11 4 Cleaning and Storing Individual Parts The procedure described here applies to the following individual parts Vessel Accessories such as blanking plugs spargers dip tubes addi tion port adapters...

Страница 192: ...cannot be physically dam aged e g by falling or prepare them for the next cultivation 11 5 Cleaning the Sensors Apart from antifoam and level sensor all sensors are cleaned and maintained according to...

Страница 193: ...m When using a soap solution 3 Then rinse the sampling system thoroughly with water INFORMATION If the test record requires that the culture is killed off after culti vation by autoclaving the culture...

Страница 194: ...a damp cloth Clean with an appropriate disinfectant as necessary 4 Clean the screen with a wipe suitable for computer or laptop screens 11 10 Maintenance Plan WARNING Non compliance of this maintenanc...

Страница 195: ...To be carried out by qualified personnel Interval Maintenance work Every 6 months Check and calibrate measuring sections temperature pH etc with a sim ulator 11 11 Decalcifying the Equipment Calcifica...

Страница 196: ...ier 4 Connect the chiller or water bath to the water inlet and outlet on the basic unit using hoses 5 To open the corresponding valves in the basic unit set the temperature on the operating panel to 5...

Страница 197: ...wn Check the fuses of the mains connection and the basic unit Qualified elec trician Power connection interrupted Check the plug and cable at the basic unit and mains socket Check mains cable for dama...

Страница 198: ...is activated and set to oxygen control via the stirrer cascade Switch cascade off and test operation via the Stirrer parameter Operator Interference Motor control is volatile irregular or stops Possi...

Страница 199: ...cause Remedy By The on site gas supply has been in terrupted Stop the Batch process Check the on site gas supply and switch it on if nec essary Operator The AirFlow and or Gas2Flow pa rameter s is are...

Страница 200: ...Check the water supply to the exit gas cooler re store it if necessary The exit gas cooler or basic unit is calcified Decal cify the equipment if necessary Operator The exit gas cooler does not cool T...

Страница 201: ...d the vessel Connect properly if necessary Remove clamps if necessary Operator Pump base acid does not operate properly Check the pump acid base functionality on the op erating panel Operator Pump hos...

Страница 202: ...e No pO2 control Possible cause Remedy Remedied by The pO2 parameter and or cascaded parameter is are not activated Activate parameters Operator The cascade settings are incorrect Check the cascade se...

Страница 203: ...By The Foam parameter is not acti vated Activate the Foam parameter Operator Pump 3 antifoam is not switched on Switch on pump 3 antifoam Operator Remedy No antifoam agent or medium supply or inadequ...

Страница 204: ...ck the function of the feed pump on the operat ing panel Operator The pump hose is damaged Replace pump head Operator Pump head does not rotate Defec tive pump head Replace pump head Operator Incorrec...

Страница 205: ...to disassembly Switch off the equipment and lock any isolation switch in the off position Physically disconnect the main energy supply from the equip ment and wait for components to fully discharge R...

Страница 206: ...firms For disposal the system units are to be disassembled and disman tled into individual material groups These materials are to be dis posed of according to the applicable national and local legisla...

Страница 207: ...rs 2 Benchtop Bioreactor Technical Data 07 February 2019 Page 205 of 214 14 Technical Data 14 1 Equipment Dimensions 565 400 631 740 NW115 145 691 NW 90 418 375 Dimensions in mm 400 455 Front view Top...

Страница 208: ...2 Benchtop Bioreactor Technical Data Page 206 of 214 07 February 2019 14 2 Dimensions of Culture Vessel The two dimension drawings show a fully equipped culture vessel ready for autoclaving Dimension...

Страница 209: ...1 Electrical Description Value Unit Voltage 120 230 VAC Frequency range 50 60 Hz Max Current 8 A Max power consumption 1 800 W 1 During heating phase vessel with max 4 L working volume at max rotatio...

Страница 210: ...cifications 14 5 1 Operating Panel Description Value HMI 7 colour touch screen Operating system Embedded Linux OPC server OPC UA Splash and dust pro tection IP 22 14 5 2 Culture Vessels Vessel Descrip...

Страница 211: ...Borosilicate glass Top plate Stainless steel AISI 316L electrolyti cally polished Components Stainless steel AISI 316L electrolyti cally polished Impellers At NW 90 PEEK At NW115 and 145 Stainless ste...

Страница 212: ...nd NW 115 Vessel size NW 90 2 Rushton impellers with 6 blades Stainless steel 316L electrolytically polished PEEK Vessel A B C 6 l TV NW 145 54 mm 11 mm 11 mm 3 0 l TV NW 115 46 mm 11 mm 11 mm 1 5 L T...

Страница 213: ...led even for gassing using air only Vessel Control range of gas flow l min 1 TV 2 Max AV 3 1 5 L 1 0 L 0 05 to 2 3 0 L 2 0 L 0 05 to 4 6 0 L 4 0 L 0 05 to 8 2 Total volume 3 Working volume 14 5 6 pH C...

Страница 214: ...pO2 sensor with built in opto electronics Type Visiferm DO ARC Manufacturer HAMILTON Measuring range 0 05 300 air saturation INFORMATION The pO2 sensors are preconfigured by unit manufacturer IN FORS...

Страница 215: ...p 4 FEED analogue BALANCED ana logue Hoses Standard Option 1 Option 2 Inside diameter 1 0 mm 0 5 mm 2 5 mm Delivery rate 1 3 5 ml min 1 1 1 ml min 1 16 1 ml min 1 Material PharMed BPT 1 Typical figure...

Страница 216: ...Minifors 2 Benchtop Bioreactor Technical Data Page 214 of 214 07 February 2019 14 8 Auxiliary Supplies pH buffers Intended use pH 4 0 pH 7 0 For calibrating the pH sensor...

Страница 217: ......

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