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ez-Control features & functionalities

Contents

Compatibility ............................................................................................................................. 2

Hardware functionalities ........................................................................................................... 2

Expandability ............................................................................................................................. 3

Software features ...................................................................................................................... 5

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Compatibility

Although the system has a very small footprint, the capabilities are beyond any other laboratory process control system. The ez-Control can control:

Autoclavable glass reactors (2 – 20 liter)

Steam in place bioreactors

Appliflex single use bioreactors

Millipore CellReady single use bioreactors

Life Technologies SUB bioreactors

PALL/ATMI PAD reactors

Hardware functionalities

The ez-Control is unique due to its flexibility and expandability. The ez-Control itself control

already consists of up to 3 pumps, pH/DO/level control and a motor controller. Temperature

control is possible via a heating blanket and/or a heat exchanger in the bioreactor or via

jacketed bioreactors.

An overview of all the ez-Control hardware functionalities:

3 fixed speed pumps (0 – 20 rpm) with ‘Easyload’ pump head 102R (standard) or

313D (advanced) with a maximum flow of respectively 33.2 or 100 mL/min.

Up to 4 rotameters or mass flow controllers (with solenoid valves) with a maximum

flow of respectively 50 or 100 L/min which can control up to 4 gasses for either

overlay aeration or sparging.

BNC connector for pH sensor.

BNC connector DO sensor.

3-pin connector for Pt-100 temperature sensors.

Temperature control via heating blanket, cool water valve or thermocirculator

2-pin connector for level sensors.

2 USB connections for configuration file import/export or sensor connections.

Water cooled exhaust gas condenser.

The ez-Control can control a wide range of stirrer motors:

o P100: 0 to 2000 rpm, Cell culture vessel up to 7 L

o P140: 0 to 2000 rpm, Microbial up to 3L

o P310: 0 to 1250 rpm, Microbial up to 7L

o P100, i=6: 0 to 300 rpm, Cell culture up to 130L

o P1000: 0 to 1000 rpm, Microbial up to 20L

o P1000, i=5: 0 to 200 rpm, Cell culture up to 1000L

The ez-Control is manufactured according the following certifications:

o GAMP4

o GAMP Class 2 (Firmware)

o 21CFR part 11 (system can be used in a 21CFR part 11 compliant

environment)

o CE certified

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o UL compliant

o CSA compliant

Firmware updates via USB.

Emergency stop button available.

Communication interface: Ethernet 10 – 100 Mbps

Expandability

The extended IO module (ADDA board) can be added to the ez-Control this will provide a lot of extra inputs and output, so a wide variety of external pumps, balances or sensors can be connected to the ez-Control:

8x analog inputs (0 – 10 Vdc)

4x analog output (0/4 – 20 mA or 0 – 5 Vdc or 0 – 10 Vdc)

8x digital inputs (24 Vdc)

8x digital outputs (dry contact, maximum switchable 24 Vdc 1A) Sensors (or transmitters) that have successfully been connected to the ADDA board are, among others:

BlueSens BCP sensors: CO2, O2, H2, CH4 , transmitter included in sensor

AppliSens redox sensor, Jumo transmitter

Mettler pH sensor, Mettler transmitter

Mettler DO sensor, Mettler transmitter

ABER biomass monitor via transmitters BM200, BM 210, BM 240,

Optek optical density sensor TF 4000, 2100

Mettler Balances, transmitter included in balance

Pendotech pressure sensor, 4-channel transmitter.

Load cells, Load cell transmitter Actuators that have successfully been connected to the ADDA board are, among others:

Any variable speed pump, Masterflex, Watson Marlow with a compatible input/output signal

fixed speed pumps, Masterflex, Watson Marlow

Gas solenoid valves

Back pressure control valve The ez-Control already has a lot of drivers pre-installed which can be connected through USB activated with a license. This enables that the following instruments can be easily connected to the ez-Control via ‘plug&play’. Moreover the USB connection allows you to see and control much more than just the process value of the sensor, e.g. tare for balances, health status of the pH, DO sensors and culture setting for biomass sensors, etc.

AppliSens LumiSens optical DO sensor

Hamilton Visiferm optical DO sensor (ARC)

Hamilton Optiferm DO sensor (ARC)

Hamilton Easyferm pH sensor (ARC)

PreSens optical DO sensor (single use)

PreSens optical pH sensor (single use)

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Polestar optical DO sensor (single use)

Polestar optical pH sensor (single use)

Buglab BE2100 non-invasive biomass sensor

Buglab BE3000 optic total biomass sensor

ABER Futura biomass sensor

USB Balances via SBI protocol (up to 4)

RS232 Balances via SBI protocol (up to 4)

HiTec Zang balance Other functions for expandability are:

A steam in place systems control board can be installed for sterilizable bioreactors

A pressure switch, used to detect the pressure limit of a single use bioreactor, can be connected to the ez-Control

External stirrer controller via analog outputs (including control loop functionality)

External temperature control unit (TCU) can be connected to the ez-Control via analog output (including control loop functionality)

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Software features

The ez-Control comes with a very intuitive and intelligent HMI and software packages. Some highlights of the software are: Adaptive auto-tuning of PID Adaptive auto-tuning of PID control is a unique feature of the Applikon biocontrollers. Adaptive control is characterized as PID control with dynamic control parameters. With adaptive PID control a fermentation or cultivation process will start with user defined or default PID settings. Due to the auto-tuning of PID control the parameter values will be optimized on regular bases. The control system is always looking for the best PID settings for the current process, guaranteeing the optimal PID settings for every single process.

Interlock limits Interlock limits, are limits that can be set to enable users to activate a certain action when a certain limit is reached (e.g. if a certain maximum critical parameter value has been reached an actuator will be stopped). Therefore a certain low and high (interlock) limit can be set with a certain dead band. When the set limit has been reach one or more actuators that have been selected will be deactivated. Once an actuator has been interlocked, it will only be reactivated when the measuring value has dropped below “the interlock minus dead band value”. See image below.

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Advanced interlock functionality In addition to the ‘regular’ interlock limits there is extra interlock functionality when a control loop is based on an analog input (e.g. external stirrer) or balance. This ‘advanced’ interlock functionality enables the user to define the output level of a specific external actuator when a certain interlock limit has been reached. Application example: The weight of the bioreactor is measured or controlled and has a Low Interlock Limit of 10 kg (10,000 g). When the Low Interlock Limit is exceeded, the liquid level in the bioreactor will have become too low for the normal stirrer speed. Using the Advanced Interlock, the stirrer speed can be limited to a certain lower value (e.g. 100 rpm).

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Total gas flow control In most cases, the number of gasses that are used in biotechnology is limited to four: • Nitrogen gas for downward dO2 control, • Air for upward dO2 control, • Oxygen gas for upward dO2 control and • Carbon dioxide gas for downward pH control. During fermentation or cultivation, the required flow of the different gasses to keep the process conditions at setpoint will vary. However, to keep the aeration of the bioreactor at a constant level (to maintain a reproducible amount of shear), it may be necessary to control the total gas flow. For this reason, the Total Gas Flow Control option has been established. Total Gas Flow control can be used in addition to other control loops (like pH, dO2 and temperature control). To the control loop, a carrier gas (like air) and one or more additiona l gasses are assigned.

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Feed control The feed control software function is enabled when you connect a balance via USB (with the license). This feature enables the user to set-up a feed profile based its measurement from the balance. The feed control algorithm is based on the increasing or decreasing weight of an addition (feed) bottle or increasing weight of the harvest bottle. The feed control can be based on the weight of the bioreactor, feed vessel or harvest vessel, depending on how the balance and the feed control are used. The flow type can either be constant, linear, exponential or logarithmic and several time segments can be set.

Configuration import/export functionality To ease the way of using similar system configurations on multiple controllers it has been enabled to save and store a system configuration on a USB stick. The saved configuration on this USB stick can easily be exported and installed on other controllers so multiple controllers are set-up with the same configuration.

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Multiple user level login Security of a control system is guaranteed via multiple user level login. Multiple user accounts can be configured for a certain system and different access levels can be assigned to each user (i.e. viewer, operator, engineer). This feature makes it possible to have different user levels with different access rights. For example, a user with viewer rights can only view the current process and not change anything. An operator can control the main process, by calibration, adjusting set points, etc. The engineer login level enables an engineer to change actuator limits and settings, set interlock limits. Also an engineer can create new users with each different access level rights. Remote login via web interface A remote login via web interface enables users to login to their control system from virtually any location. The HMI of the ez-Controller can be accessed from any computer or tablet with an internet connection. This allows the users to check and control their process remotely if necessary. The ez-Control web interface has all functionalities of the ez-Control and has a lay-out that’s designed for use on bigger screens.

Firmware update via USB Firmware updates via USB makes it very easy for any service engineer to update all the control systems of a customer in just a few minutes. New updates can easily be installed on ez-Controllers simply by plugging in an USB stick with the latest firmware version. Other software features are, among others:

Multiple data displays: synoptic, trends, bar graph, table overviews

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Quick view of current process parameters, setpoints and actuators

Maximum of 26 control loops o 5 standard: pH, temperature, dissolved oxygen, foam/level, agitation o 8 freely configurable using extended I/O o 13 for different USB sensors

Different types of control o PID for pH, temperature, dissolved oxygen, agitation o PID for all sensors connected via Extended IO module or USB o On/off control for level/foam o Setpoint control for external actuators such as stirrers or TCU o Flow control for feeding or harvesting

Possibility for pressure switch control loop

Temperature control: Cooling water +5 ⁰C up to 70 ⁰C

Dose monitor for all actuators

Totalizer for dosed volumes for pumps and gasses

Pump priming

Timer control for pumps and gasses

Lower and upper limits settings for parameters including alarms

Alarm overview

Low gas flow alarm for MFC’s.

Level sensor high and low sensitivity for foam / level control

Temperature compensation for pH and DO sensors

Sensor replacement in a control loop (especially for control loops based on analog inputs)

Inhibit function for actuators (function can be used to completely ensure that certain actuator, e.g. pump, stirrer, MFC, is completely 0% when set at 0%

Actuator calibration (e.g. for pumps)

OPC server for communication with SCADA/PIMS software

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HMI actuator settings enable users to set actuator names and units according to user definitions

Local data storage and trend view up to 72 hours

Screen cleaning interface

Date & time settings

Easy activation of additional licenses

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PIMS/SCADA software

Standard 2 SCADA/PIMS software packages are available for controlling ez-Controllers. But the ez-Control is compatible with any software package compatible with OPC server communication. Standard the ez-Controller is sold with Lucullus Lite. Lucullus Process Information Management System: Turning Data into Information

Lucullus PIMS software allows the user to monitor and control bioprocesses and offers an extensive toolbox for analyzing process data cross platforms. Process information can be generated based on data generated in different brands of bioreactor types and wide range of different cultivation volumes. The software includes functionality for Design of Experiments, Reactor Planning, Media Preparation and Tracking, Parallel Processing, SCADA, Data Mining and Batch Reporting. The combination of the software with the broad range of Applikon Bioreactor Systems offers the user a unique system for validatable fast track development and basic research. The ever increasing amount of process data generated by more sensors in smaller parallel bioreactor systems needs advanced software to turn this data into useful information. Lucullus PIMS offers a new dimension in data processing. Data management and data analysis is key for the future of R&D and process development in pharmaceutical industry. The main modules of Lucullus PIMS are:

Planning, activities around the planning of recipes, reactor allocation and Design of Experiments

Preparation, media preparation, storage and component trace-ability

Execution, process execution and data presentation and storage

Evaluation, data analysis, presentation, automatic reporting, modelling and comparison of data between different cultures

BioXpert W7

BioXpert is a software tool to control bio-processes and to store the process data. The software is designed specifically for biotech researchers and operators in the production environment. The logical structure of the program and the user-friendly interface allows the program to be used by anyone. That is why over 1,000 packages of our BioXpert software are in use worldwide. The software is easy to operate and has extensive functionality for monitoring, collecting and storing data and controlling processes. This allows any bioprocess to be easily optimized and controlled using Applikon software. The BioXpert W7 allows the user to operate the bioreactor systems in compliance with the FDA's 21 CFR part 11 guidelines. Via web browser technology the BioXpert W7 data is accessible throughout a network using Remote Access. To create process reports in compliance with 21 CFR part 11 BioXpert W7 uses a separate Report Generator.