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In touch with life®
We Know Bioprocessing
Parallel Cultivation of Microorganisms usingSingle-use Mini BioreactorsBio Base NWE Workshop & CLIB-Forum Scale-up & Scale-down
Creative Campus Monheim, Germany | April 3, 2014 | Sebastian Kleebank
> Introduction
> Scalable Systems
> Single-use options
> Software solutions
> Summary> Summary
4
Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors
DASGIP®
Information and Process Technology GmbH
Excellence in hardware & software solutions
> Founded in 1991 as a computer and software engineering company
> Developing benchtop bioprocessing solutions since 1994
> Commitment to customers and product for more than 20 years
> Platform technology for industry leaders in North America, Europe and Asia
Introduction
> Platform technology for industry leaders in North America, Europe and Asia
> An company since Jan 1st, 2012
5Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Introduction
DASGIP® – Part of Eppendorf Group
Manual pipettes Electronic pipettes Pipette tips Pipette calibration Bottle-top dispensers
CombitipsDispensersAutomated pipetting
Han
dli
ng
Liq
uid
Han
dli
ng
6Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Single-use vessels CO2 incubators Biological shakers Microinjectors Microinjectors Microcapillaries ElectroporatorsFermentors/ bioreactors
CentrifugesUltra-low temp-erature freezer
Mixers Spectrometers,Photometer and cuvettes
Vacuum concentrators PCR devices PCR and deepwell plates
Tubes
Sam
ple
Han
dli
ng
Cell
Han
dli
ng
History of Bioprocessing at Eppendorf
Introduction
70 years of experience in the life science market
Foundation of Eppendorf-
Netheler-Hinz GmbH
Acquisition of New Brunswick Scientific Co
Acquisition of DASGIP GmbH
7Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
1946 2007 2012 20131991
Foundation of DASGIP GmbH
1945
Foundation of New
Brunswick™ Scientific Co
Eppendorf AG Bioprocess
Product Lines:
New Brunswick
DASGIP
DASware®
BioBLU®
> 2700 employees in more than 25 countries
> North American, European, and Asian Headquarters
Introduction
Eppendorf – There When You Need Us
> Global sales and service
> Training and application labs throughout the world
8Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
What is located in Juelich?
Introduction
> Eppendorf Bioprocess Center:
PAN European Sales and Service Team for
New Brunswick & DASGIP bioprocess product
lines
> DASGIP GmbH:
9Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
> DASGIP GmbH:
Competence Center for Small and Parallel
Bioreactors/Fermentors
Competence Center for Advanced Interfacing
Our 3S Value Proposition
Introduction
Scalable Systems
Comprehensive
Eppendorf bioprocess
systems cover a wide range
of working volumes in
Single-Use Options
Ready-to-Use
Ready-to-use single-use
bioreactors of different
volumes complement the
Software solutions
Innovative
Comprehensive software
packages offer innovative
solutions for advanced
10Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
of working volumes in
autoclavable, single-use and
SIP.
scale range. process control and
information management.
> Introduction
> Scalable systems
> Single-use options
> Software solutions
> Summary> Summary
11
Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors
Bioreactor Solutions
> Glass and stainless steel bioreactors with working volumes of 60 mL – 2400 L
> Single-use bioreactors with working volumes of 65 mL – 1.25 L (microbial application) and 100 mL – 40 L (cell culture)
Scalable systems
12Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
DASGIP® Product Lines
> DASbox Mini Bioreactor System
> DASGIP Parallel Bioreactor
Systems
Scalable systems
Systems
> DASGIP Control and DASware
Solutions
13Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
DASbox® Mini Bioreactor System
Optimal for screening, characterization and optimization
Scalable systems
14Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
Mini Bioreactor Solutions
DASbox® Parallel Mini Bioreactor System
> Operation of 4, 8, 12 or more vessels in parallel
> Working volumes of 60 - 250 mL
> Designed for cell culture and microbial applications
Scalable systems
applications
> Glass and single-use vessel options
> Optimal tool for DoE and scale-down approaches
15Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
DASbox® – Features
Scalable systems
Multifunctional storage unit
Local Display
Integrated Gas mixing
Feeding & Monitoring module
16
module
Liquid free temperaturecontrol unitDetachable media
bottle container and bioreactor
carrier
Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
DASbox® Mini Bioreactor
> Glass body & stainless steel head plate
w/easy to handle screw cap
> Working volume 60 – 250 mL (H/D 2:1),
Total volume 350 mL
> Overhead drive using
Scalable systems
miniature lip seal assembly
with Rushton and/or marine impellers
> Liquid free exhaust condenser
> Utilizing off-the-shelf pH and DO sensors
(120mm long, 12mm diameter)
17Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Small- and Bench scale Bioreactor Solutions
DASGIP® Parallel Bioreactor Systems
> Parallel operation of 4, 8 or more vessels
> Working volumes of 35 mL – 3.8 L
> Designed for fermentation, phototrophic cultivation, cell culture, and stem cell
Scalable systems
cultivation, cell culture, and stem cell applications
> Glass and single-use vessel options
> Highly flexible due to modular design of monitoring and control units
18Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
Benefits
> Small footprint
> Modular design
> Effective operation
Scalable systems
> Full integration
> Easy to handle
19Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
Basic Technical Features
> Individual temperature and
agitation control
> Up to 6 liquid feeds per vessel
> pH control with CO2, acid and/or
base addition
Scalable systems
> DO control by stirring speed, oxygen
concentration and/or gas flow rate
> Redox/ORP monitoring and control
> Gassing to sparge and/or overlay
20Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
Advanced Technical Features
> Miniature peristaltic pumps using variable
speed drives
> TMFC or rotameter/solenoid gassing
> O2 and CO2 exhaust analysis with online OTR,
CTR and RQ calculation
Scalable systems
> Overhead drive or magnetic stirring
> Level control or anti foam sensor
> Optical density measurement
> Illumination using LED light sticks
21Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
Bioreactor Designs
> Mammalian cell culture
> suspension
> adherent
> Microbial fermentation
> aerobic
Scalable systems
> aerobic
> anaerobic
> Phototropic cells and organisms
> Stem cells
22Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
Scale-DownExample: E. coli Fermentation
Scalable systems
Scale-Down of a 2 L amino acidfermentation process
23
Cell dry weight (X), product concentration (P) and specific product yield (YP/X), each normalized to the 2 L system
Eppendorf Application Note No. 290
Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Scalability – BiomassParallel E. coli K12 cultivationDry cell weight [g/L] , 22.4 h ± 1.0 h after inoculation
Scalable systems
45,0
50,0
24Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
33,930,9 32,4 31,8
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
40,0
SR0250ODLSn = 3
SR1000ODLSn = 4
BioBLU 0.3fn = 4
BioBLU 1fn = 4
dry
cell w
eig
ht
[g/L]
> Introduction
> Scalable systems
> Single-use options
> Software solutions
> Summary> Summary
25
Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors
BioBLU® Rigid Wall, Stirred-Tank Single-Use Vessels
> Various types for cell culture and microbial applications, including packed-bed version
> Working volumes of 100 mL – 40 L (cell culture) and 65 mL – 1.25 L (microbial applications)
> To be operated with DASbox, DASGIP Parallel Bioreactor Systems and CelliGen® BLU or 3rd
Single-use options
Bioreactor Systems and CelliGen® BLU or 3rd
party systems
> Non-invasive or industry standard sensor technology
26Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProduct/Process
DevelopmentPilot Scale Production
BioBLU® – A Growing Family
> Proven performance and scalability of stirred-tank design
Single-use options
Combining polymer expertise and bioprocess know-how Eppendorf offers the industry’s most complete portfolio of single-use bioreactors for RD, PD & pilot scale!
design
> User-friendly set-up for rapid turnover, shorter development times and lower operating costs
> USP Class VI and animal component free materials making vessels appropriate for GMP production
> Adapter kits available for 3rd party bioprocess systems
27Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
BioBLU® 0.3 Single-Use Vessels
> Small scale single-use vessel
> Classic stirred-tank bioreactor design
> Designed for DASbox Mini Bioreactor System
providing industry standard control capabilities
> Cell culture, microbial and packed-bed versions
Single-use options
> Cell culture, microbial and packed-bed versions
available
> Working volume:
> 65 - 250 mL (BioBLU 0.3f)
> 100 - 250 mL (BioBLU 0.3c)
> 250 mL (BioBLU 0.3p)
28Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Full featured
Liquid-free exhaust condenser (Peltier)
BioBLU® 0.3 – Features
Single-use options
Gas inlet to submersed and headspace gassing
Magneticallycoupled
drive assembly
Rigid wallsingle-use stirred-
tank bioreactor
Full featuredhighly integrated head plate
Heating and cooling by liquid-free DASbox temperature control
29Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
BioBLU® 1 Single-Use Vessels
> Bench scale single-use vessel
> Classic stirred-tank bioreactor design
> Designed for DASGIP Bioblock providing industry
standard control capabilities
> Cell culture and microbial versions available
Single-use options
> Cell culture and microbial versions available
> Working volume:
> 250 mL – 1.25 L (BioBLU 1f)
> 320 mL – 1.25 L (BioBLU 1c)
30Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
BioBLU® 5 Single-Use Vessel
> Bench scale single-use vessel
> Classic stirred-tank bioreactor design
> Parallel operation and calibration with the
DASGIP Parallel Bioreactor System
> Pitched blade (BioBLU 5c) and packed-bed
Single-use options
> Pitched blade (BioBLU 5c) and packed-bed
(BioBLU 5p) versions available
> Working volume: 1.25 – 3.75 L
31Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Scalability – BiomassParallel E. coli K12 cultivationDry cell weight [g/L] , 22.4 h ± 1.0 h after inoculation
Single-use options
45,0
50,0
32Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
33,930,9 32,4 31,8
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
40,0
SR0250ODLSn = 3
SR1000ODLSn = 4
BioBLU 0.3fn = 4
BioBLU 1fn = 4
dry
cell w
eig
ht
[g/L]
> Introduction
> Scalable systems
> Single-use options
> Software solutions
> Summary> Summary
33
Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors
More than SCADA
Eppendorf offers a flexible range of bioprocess software solutions for Supervisory Control and Data Acquisition (SCADA) and Data Management
Software solutions
34Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
DASGIP ControlSophisticated Monitoring and Control Capabilities
BioCommandConfigurable Control Strategies,
Data logging , Alarms etc.
DASwareComprehensive Data and Information Management
New Brunswick RPCAdvanced Local Control
Comprehensive Bioprocess Information Management
DASware®
Software solutions
Remote monitoring and control via PC, Notebook, Netbook or with the DASGIP iApp via iPhone®, iPod® and iPad®
Applies Design of Experiment (DoE)
35Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
R&D and Scale DownProduct/Process
DevelopmentProcess
DevelopmentPilot Scale Production
Seamless integration of external lab devices for process automation and feedback control loops
Integration into process control systems and corporate historians
Comprehensive and user-friendly information management solution for bioprocessing
Integration of different bioreactor control units - the gateway to benefit from DASware functionality on 3rd
party bioreactor controllers
DASGIP® Control –At the Core of All DASGIP® Systems
Software solutions
In situ sensors
Point of Measurement TrendingPoint of control
Supervisory Control and Data Acquisition (SCADA)
Control strategies & automation
Historian
Bioprocessanalytical
instruments
Recipe management
36Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
More than SCADA
> Recipe management:
load & store recipes and
configurations at different sites
> Integrated historian with 70+ data
tracks per bioreactor
Software solutions
tracks per bioreactor
> Integrated alarms & events
> Highly configurable control strategies
with data driven control decisions
37Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Fully Integrated Workflow
Software solutions
Formulate recipe at first system/facility
Send recipe to second system/facility (via email or DASware discover)
Point
38
system/facility (via email or DASware discover)
Load and execute recipeCollect online and offline data
Send data to first system/facility for analysis(via email or DASware discover)
Click
Grow
Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
> Introduction
> Scalable systems
> Single-use options
> Software solutions
> Summary> Summary
39
Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors
Culture
PassageSeed
Fermentors and Bioreactors
Freezers
Manual Liquid Handling
Centrifugation
Shakers and CO2 incubators
Summary
The Right Tools, Every Step of the Way
Manipulate
Analyze
Store
Automated Liquid Handling
Freezers
Analysis
Services
Transfection
Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014 40
Scalable Systems –Total Upstream Solutions
Summary
R&D and Scale Down
Process Development
41Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014
Pilot/ Production
Process Development
We Know BioprocessingThank you
Trademarks
CelliGen® and BioCommand® are registered trademarks of Eppendorf, Inc., Enfield, Connecticut (USA). DASGIP®, DASbox® and DASware® are registered trademarks of DASGIP Information and Process Technology GmbH, Juelich, Germany.
Eppendorf® the Eppendorf logo, BioBLU®, and In touch with life® are registered trademarks of Eppendorf AG, Hamburg, Germany. New Brunswick™ is a trademark of Eppendorf AG, Hamburg, Germany.
All rights reserved, including graphics and photos. Copyright © 2014 by Eppendorf AG.
43Eppendorf AG | Parallel Cultivation of Microorganisms using Single-use Mini Bioreactors | Sebastian Kleebank | April 3, 2014