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BioLector® I48 Parallel Microbioreactors
High-Throughput Real-Time MonitoringScalabilityAutomation
m2p-labs | The Microbioreactor Company www.m2p-labs.com
Microbioreactors | BioLector® I
High Information Content for fast SelectionBioLector® I
Applications
The BioLector® I is the first bench top microfermentation system to perform high-throughput fermentations together with online monitoring of the most common fermentation parameters (biomass, pH, DO and fluorescent molecules).
The system is based on a standard microtiter plate format and operates with non-invasive, optical sensors. Due to the continuous and rigorous shaking during the optical measurements and over the whole experimental time it is ideally suited for aerobic and anaerobic cultures. For the first time,real time culture monitoring at a massive parallel scale becomes possible!
Measurements
• Cell line and strain screening• Media screening and optimization• Fermentation parameter optimization• Anaerobic and microaerophilic fermentations• Synthetic and systems biology • Statistical design of experiments (DoE)• Growth characterization• Protein building kinetics• High-throughput protein expression• Enzyme and cell activity tests• Functional genomics• Proteomic studies• Inhibition and toxicity tests• Quality control
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Multiparameter-Monitoring in the FlowerPlate®
48 well FlowerPlate®, 1000 μL, 800 rpm, 37 °C
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Microbioreactors | BioLector® I
48 Parallel Microbioreactors
Features
Online Parameters
• Biomass concentration• pH-value• Dissolved oxygen (DO)• NAD(P)H and riboflavins• Fluorescent molecules (GFP, YFP, DsRed ...)
System Performance
• Working volume of 800 – 2400 μL
• 48 parallel microreactions
• No foaming problems
• Broad range of kLa values (25 – 600 1/h)
• Continuous gas exchange and oxygen supply
• Equal power input to each reactor
• Defined engineering parameters and scalability
• Controlled gas atmosphere (CO2, O2 and N2)
• Humidity control (> 75 % rH)
• Temperature control (20 – 50 °C)
Operating Principle
Multiparameter FlowerPlate® with Optodes
DissolvedoxygenBiomass & fluorescencepH-value
• Real time kinetics out of 48 parallel fermentations• Microfermentation in standard MTP format• High-throughput and easy automation• Broad linear range for biomass (up to 100 g/L CDW, 600 OD)• Excellent reproducibility (CV < 5 %)• No edge effects• Continuous shaking operation (no artifacts)• Defined mass transfer conditions (no O2-limitation)• Easy scale up to lab-fermenters• Industry leading data analysis software• Fast and easy data analysis included• A valuable tool for PAT and QbD
Smaller and Smarter
Advantages
Data Analysis with the BioLection Software
Intelligent Software
Microbioreactors | BioLector® I
BioLector® I | m2p-labs
EUROPE [email protected]
Technical Specifications BioLector® I
SYSTEM Art.-No. G-BL-100
Operation conditions Optical measurements
Plate format 48 Filter configuration up to 6 different filters
Volume 800 – 2400 μL (depending on microtiter plate) Wavelengths 365 nm – 800 nm
Temperature 5 °C below room temperature, max. 50 °C MTP read time down to 3 min/parameter/48 wells
Gas atmosphere Only air (optional modules, see below) Linear range of cell counts 0.2 – 600 OD (0.1 – 100 g/L CDW)
Humidity > 75 % rH
Orbital shaker 400 – 1500 rpm at 3 mm (diameter)
Modules pH / DO Monitoring
Dimensions (W × H × D) 795 mm × 333 mm × 470 mm Calibration Precalibrated plates
Weight Approx. 40 kg Measurement range pH 3.0 – 6.0 or 4.5 – 7.5 depending on plate type
Power source 100 – 240 V (50/60 HZ) Measurement range DO 0 – 100 % oxygen saturation
Interface Ethernet Application mode Disposable technology
Ambient conditions 15 – 40 °C, max. 75 % rH
Automation Optionally, the BioLector® can be integrated into the RoboLector® liquid handling systems#
ORDERING
OPTIONAL MODULES
It is possible to combine all types of modules (AN, O2, CO2, FRET) in one device.
Leasing option available
Art.-No. Module description Application Additional feature Note
E-AN-200 BL-Module for anaerobic cultivation
Strict anaerobic fermentation + small, controlled gas flow
Gassing with pure N2 or CO2 or other defined gases, controlled gas flow through mass flow controller (1 – 10 mL/min)
E-O2-100 O2-upregulation module Fermentation with O2 enriched air Control of gas atmosphere: 21 – 35 % O2
Only one O2 sensor can be installed in the device
E-O2-25 O2-downregulation module Fermentation at O2 reduced air, microaerophilic conditions
Control of gas atmosphere: 2 – 21 % O2
Only one O2 sensor can be installed in the device
E-CO2-10 CO2-upregulation module Fermentation with CO2 controlled gas atmosphere
Control of gas atmosphere: 0 – 10 % CO2
E-AN-201 BL-Preparation: anaerobic cultivation
Preparation for later addition of anaerobic module
Easy integration of anaerobic module on site
E-AN-202 Anaerobic cultivation set Later addition of: Strict anaerobic fermentation + small, controlled gas flow
Gassing with pure N2 or CO2 or other defined gases
Anaerobic module for integration on site
E-FRET-100 BL-Option for FRET measurement
FRET measurements in BioLector® (1 × excitation / 2 × emission fluorescences)
Additional measurement of a second, synchronous emission wavelength
Two photomultipliers installed
E-OP-101-199 LED/Filter Module Measurement of additional fluorescences in the BioLector®
Measurement at additional wavelengths
Ask your sales manager for available modules
E-OP-900 Notebook for BioLector® System
Notebook for data analysis Data analysis and visualization on a separate computer
BioLector® ProMicrofluidic Bioprocess Control
m2p-labs | The Microbioreactor Company www.m2p-labs.com
32 Parallel MicrobioreactorspH ControlContinuous FeedingOnline MonitoringScalability
Microbioreactors | BioLector® Pro
Full Bioprocess Control On-the-PlateBioLector® Pro
Applications
The BioLector® Pro is the first microbioreactor system combining the established BioLector® technology with an innovative microfluidic chip.
The system is based on a standard microtiter plate format and operates with non-invasive, optical sensors. The disposable 48 well microtiter plate of the BioLector® Pro features online measurements of biomass, fluorescence, pH and DO and simultaneously controls the pH and feeding rates through micro-valves and microfluidic-channels. For the first time, these unique microfluidic components allow continuous feeding and pH control in standard microtiter plates. There is no tubing and no liquid handling needed anymore; everything is part of the gamma radiated ready-to-use plate!
Measurements
• Fed-batch development• pH profiling• Feeding rate optimization• Media screening and optimization• Fermentation parameter optimization• Cell line and strain screening• Anaerobic and microaerophilic fermentations• Synthetic and systems biology• Statistical design of experiments (DoE)• Growth characterization• High-throughput protein expression• Enzyme and cell activity tests• Functional genomics• Proteomic studies• Inhibition and toxicity tests• Quality control
E. coli (two triplicates using different P&I settings) WR medium, 37°C, 800 rpm, pHset = 6.4, One-sided pH control (NaOH), Feeding rate = 5 uL/h Glucose (500g/L), Start feed at 5h, Round Well Plate
BioLector® Pro – E. coli Fed-batch Fermentation
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Batch
Microbioreactors | BioLector® Pro
32 Parallel Microbioreactors
Features
Online Measurement
• Biomass concentration• pH value• Dissolved oxygen (DO)• NAD(P)H and riboflavins• Fluorescent molecules (GFP, YFP, DsRed ...)• Temperature• Humidity• O2 in head space atmosphere• CO2 in head space atmosphere
Online Control
• pH value
• Feeding
• Shaking speed
• Temperature
• Humidity
• O2 in head space atmosphere
• CO2 in head space atmosphere
System Performance
• Working volume of 800 – 2400 μL
• 32 parallel microreactions
• 16 reservoir wells
• Individual pH control
• Continuous individual feeding
• No foaming problems
• Broad range of kLa values
(25 – 600 1/h)
• Continuous gas exchange and
oxygen supply
• Equal power input to each reactor
• Defined engineering parameters
and scalability
• Controlled gas atmosphere
(CO2, O2 and N2)
• Feeding modes: constant, linear,
exponential or signal triggered
Operating Principle
Microfluidic Control on a FlowerPlate® with Optodes
Well Reservoir 2 Reservoir 1
pH line
Feed line
Dissolved oxygen Biomass & fluorescence pH value Micro-valves
• Real time kinetics in 32 parallel fermentations• Microfermentation in standard MTP format• Batch and fed-batch cultivation• Control of pH on-the-plate• Continuous controlled feeding on-the-plate• DO- and signal-triggered feeding• High-throughput and easy automation• Broad linear range for biomass detection (up to 100 g/L CDW, 600 OD) • Small volume (800 – 2400 μL)• Excellent reproducibility (CV < 5 %)• No edge effects• Continuous shaking operation (no artefacts)• Defined mass transfer conditions (no O2-limitation)• Reliable scale up to benchtop fermenters• Industry leading data analysis software• Fast and easy data analysis included• A valuable tool for PAT and QbD
Smaller and Smarter
Advantages
Data Analysis with the BioLection Software
BioLector® Pro | m2p-labs
Intelligent Software
Microbioreactors | BioLector® Pro
EUROPE [email protected]
Technical Specifications BioLector® Pro
ORDERING
OPTIONAL MODULES
It is possible to combine all types of modules (O2, CO2, FRET) in one device.
Leasing option available
Art.-No. Module description Application Additional feature Note
E-O2-25 O2-downregulation module Fermentation at O2 reduced air, microaerophilic conditions
Control of gas atmosphere: 2 – 21 % O2
E-CO2-10 CO2-upregulation module Fermentation with CO2 controlled gas atmosphere
Control of gas atmosphere: 0 – 10 % CO2
E-AN-200 BL-Module for anaerobic cultivation
Strict anaerobic fermentation + small, controlled gas flow
Gassing with pure N2 or CO2 or other defined gases
Operates only with standard 48 well plate
E-FRET-100 BL-Option for FRET measurement
FRET measurements in BioLector® (1× excitation / 2× emission fluorescences)
Additional measurement of a second, synchronous emission wavelength
Two photodiodes installed
E-OP-101-199 LED/Filter module Measurement of additional fluorescences in the BioLector®
Measurement at additional wavelengths
Custom made filter modules available
SYSTEM Art.-No.: G-BLMFL-101
Operation conditions Optical measurements
Plate format 48 (32 reactor, 16 reservoir wells) Filter configuration up to 6 different filters
Volume 800 – 2400 μL (depending on microtiter plate) Preinstalled filters Biomass, Riboflavin, pH and DO
Temperature, minimum 5 °C below RT (room temperature) Wavelengths 365 nm – 800 nm
Temperature, maximum 50 °C MTP read time down to 2 min/parameter/32 wells
Gas atmosphere Only air (optional modules, see below) Linear range of cell counts 0.2 – 700 OD (0.1 – 120 g/L CDW)
Humidity > 75 % rH
Orbital shaker 400 – 1500 rpm at 3 mm (diameter)
Feed rate Two feed lines/well with dosing down to 100 nL, max. 100 μL/h
pH control Over the whole measurement range
Modules Monitoring / Control
Dimensions (W × H × D) 795 mm × 333 mm × 470 mm Calibration Precalibrated plates
600 mm × 478 mm × 450 mm add. valve control unit Measurement range pH 3.0 – 6.0 or 4.5 – 7.5 depending on plate type
Weight Approx. 40 kg Measurement range DO 0 – 100 % oxygen saturation
Power source 100 – 240 V (50/60 Hz) pH control By acid or/and base
Interface Ethernet Application mode Disposable technology
Ambient conditions 15 – 40 °C, max. 75 % rH
Automation Optionally, the BioLector® can be integrated into the
RoboLector® liquid handling systems.
Note: The BioLector® Pro includes the BioLection software pre-installed on a notebook.
FlowerPlate®
Enlighten your Research with our Flowers
High Oxygen TransferHigh-Throughput FermentationReal-Time MonitoringScalability
FlowerPlate®
The Microbioreactor Company www.m2p-labs.com
www.m2p-labs.com
FlowerPlate®
Your Cells Will Love It!
The FlowerPlate® is a new microtiter plate which combines unique mass transfer performance with online measurements of the most relevant fermentation parameters. Based on a standard SBS footprint the flower geometry was picked out of more than 30 different well geometries. The flower shape acts similarly to baffles in shake flasks and increases mixing and gas/liquid mass transfer. It’s perfomance surpasses all common microtiter plate formats providing a unique solution for cell growth and biocata-lytic reactions.
A Unique Performance• High mass transfer OTR > 0.11 mol/L/h (kLa > 600 1/h)• Multiparameter reading possible in 48 parallel bioreactors• Wide volume range (800 – 1500 µL) • Scalability to production fermenters• No optical cross talk • Effective mixing• No foaming or spilling• Continuous contact of liquids to optodes
Measurement Principle
Measurement Example
Ordering Info
EU: +49-2401-805-330
USA: +1-631-501-1878
48 Well FlowerPlate®
incl. pH and DO optode / well MTP-48-BOH
incl. DO optode / well MTP-48-BO
incl. pH optode / well MTP-48-BH
transparent bottom, without optodes MTP-48-B
black bottom, for offline cultivation MTP-48-OFF
DissolvedOxygen Biomass & FluorescencepH-value
Time [h]
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EUROPEm2p-labs GmbHArnold-Sommerfeld-Ring 2 | 52499 Baesweiler | Germany Phone +49-2401-805-330 | Fax [email protected]
USAm2p-labs, Inc.400 Oser Ave, Suite 1650 | Hauppauge, NY 11788 | USAPhone +1-631-501-1878 | Fax [email protected]
Round Well PlateFirst Choice for Deeper Knowledge
Low to Medium Oxygen TransferHigh-Throughput FermentationReal-Time MonitoringScalability
Round Well Plate
The Microbioreactor Company www.m2p-labs.com
www.m2p-labs.com
Round Well PlateMore Insights in Less Time
The Round Well Plate is a new deepwell microtiter plate which combines high-throughput bioprocessing with online measure-ments of the most relevant fermentation parameters, e.g. biomass and protein concentrations as well as pH and DO. Based on a stan-dard SBS footprint, the round geometry is ideally suited for low oxygen demands or microaerophilic cultures as well as for higher viscosities. The continuous shaking process delivers sufficient oxygen for slowly growing cells and avoids the sedimentation and aggregation of cells. The Round Well Plate is an excellent cul-tivation platform to fulfill todays needs in screening and early bioprocess development.
A Unique Performance• Multiparameter reading possible in 48 parallel bioreactors• Broad range of kLa values (25 – 170 1/h)• Wide volume range (800 – 2400 µL) • No spilling • No optical cross talk• Effective mixing • No foaming• Continuous contact of liquids to optodes• Scalability to production fermenters
Measurement Principle
Measurement Example
Ordering Info
EU: +49-2401-805-330
USA: +1-631-501-1878
48 Well Round Well Plate
incl. pH and DO optode / well MTP-R48-BOH
incl. DO optode / well MTP-R48-BO
incl. pH optode / well MTP-R48-BH
transparent bottom, without optodes MTP-R48-B
black bottom, for offline cultivation MTP-R48-OFF
DissolvedOxygen Biomass & FluorescencepH-value
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Medium0.5 × 106 cells mL-1
0.75 × 106 cells mL-1
1.0 × 106 cells mL-1
1.25 × 106 cells mL-1
1.5 × 106 cells mL-1
Time [h]0 24 48 72 69 120 144 168 192
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Figure 2: Growth studies with Sf-9 suspension cells with different inoculation cell densities in 48-well cell culture plates.
Growth studies with Sf-9 suspension cells with different inoculation cell densities in 48-well Round Well Plate.
EUROPEm2p-labs GmbHArnold-Sommerfeld-Ring 2 | 52499 Baesweiler | Germany Phone +49-2401-805-330 | Fax [email protected]
USAm2p-labs, Inc.400 Oser Ave, Suite 1650 | Hauppauge, NY 11788 | USAPhone +1-631-501-1878 | Fax [email protected]
RoboLector®
Automated Fermentation
m2p-labs | The Microbioreactor Company www.m2p-labs.com
High-ThroughputReal-Time MonitoringScalabilityAutomation
Automation | RoboLector®
The Robotic Solution for your FermentationRoboLector®
Applications
The RoboLector® consists of a standard liquid handling robot and a BioLector®. This unique automated fermentation platform combines the high-throughput fermentation and online monitoring capability of the BioLector® with the precise and accurate liquid handling of a robotic system. For the first time, automated fermentations in microbioreactors fulfill the requirements of modern fermentation processes and bioprocess development. The RoboLector® autonomously prepares media compositions, amongst others, from design of experiments (DoE) tests followed by an online-monitored high-throughput fermentation. Furthermore, pH adjustments can be made, inducers as well as feed solutions can be added to each process according to a pre-defined schedule or t riggered by online process signals. Automated sampling into various targets including a freezing and a cooling station facilitates optimal process monitoring and control.
Measurements
C. glutamicum ATCC 13032 pXMJ 19: SP-Cutinase T=30 °C, 1200 rpm, 3mm, 1 mLmedia: CG XII, 0.5 mM IPTG
Source: Rohe et al. Microbial Cell Factories 2012, 11:144
• Automated sampling• Automated induction• Induction profiling• Synchronized process manipulation• pH profiling• Feeding profiling• Media preparation• Triggered process manipulation• Process characterization• High-throughput protein expression• Automated upstream processing with microbial cultures• Combination with automated downstream processing
Triggered controlled sampling
12
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-1]
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Automation | RoboLector®
Features
Fermentation Modes
• Biomass dependent sampling or dosing• Time dependent sampling or dosing• DO or time controlled feeding• Fed-batch with bolus feeding• Repeated fed-batch
Online Trigger Signals
• Biomass concentration• pH, DO (using optodes)• Fluorescent molecules (GFP, YFP, DsRed ...)• NAD(P)H and riboflavins• Process or induction time• Working volume
Access of pipetting tips to the shaking microtiter plate in the BioLector®
Operating Principle
Full Process Understanding
• Automated upstream processing of up to 48 parallel fermentations• Continuous operation 24 hours/day and 7 days/week• Plug & Play disposable technology• Design of experiments (DoE)• Detailed process understanding in short time• Excellent pipetting accuracy (< 5 %) and reproducibility (CV < 5 %) • Flexible tip configuration (1–8 tips)• Reliable scale up to lab-fermenters• Fast and easy data analysis• A valuable tool for PAT and QbD• Combination with HT-downstream • Processing units possible (for custom made solutions1)
Precision in Fermentations
Advantages
RoboLector® Agent Software for Fermentation Process Design
Process Design Software
Automation | RoboLector®
RoboLector® | m2p-labs
Technical SpecificationsRoboLector®
Robo S
Art.-No. G-RL-100
RoboLector® LArt.-No. G-RL-200
RoboLector® XL Art.-No. G-RL-800
dies
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ite k
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Sch
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!!!
The RoboLector® is a proprietary combination of a liquid handling robot and the BioLector®.
1 Optionally, the BioLector® can be integrated into other standard liquid handling systems.
BioLector® not integrated BioLector® integrated BioLector® integrated
Operation Conditions BioLector®
Plate format 48 48 48Working volume 800 – 2400 µL 800 – 2400 µL 800 – 2400 µL
Temperature, minimum 5 °C below RT (room temperature) 5 °C below RT (room temperature) 5 °C below RT (room temperature)
Temperature, maximum 50 °C 50 °C 50 °C
Gas atmosphere Various, see BioLector® Various, see BioLector® Various, see BioLector®
Humidity > 75 % rH > 75 % rH > 75 % rH
Orbital shaker 400 – 1500 rpm at 3 mm (diameter) 400 – 1500 rpm at 3 mm (diameter) 400 – 1500 rpm at 3 mm (diameter)
Liquid Handler
Robotic arms 1 1 1Arm type Liquid handling Liquid handling Liquid handling
Pipetting channels 1 2 or 4 8
Pipetting volume
with disposable tips 10 – 950 µl 10 – 950 µl 10 – 950 µl
with washable tips 10 – 1000 µl 10 – 1000 µl
Liquid level detection By capacity in conductive liquids By capacity in conductive liquids By capacity in conductive liquids
Type of tips Disposable Fixed, disposable and mixed Fixed, disposable and mixed
Max. deck positions (SBS footprint) 5 16 20
Modules
Dimensions (WxDxH) 566 × 460 × 649 mm 1788 × 825 × 920 mm 2009 × 825 × 920 mm
Weight (excl. BioLector®) 33.5 kg ca. 84 kg ca. 102 kg
Power source 100 – 240 V (50/60 Hz) 100 – 240 V (50/60 Hz) 100 – 240 V (50/60 Hz)
Optional modules Different racks Different racks, plate cooler 4 – 50 or –15 °C, orbital shaker (2 mm shaking diameter)
Different racks, plate cooler 4 – 50 or –15 °C, orbital shaker (2 mm shaking diameter)
Other Fits in most standard clean benches
Software Features
Media preparation (disposable tips)
DoE import
Signal triggered actions
Dependent trigger
DO-controlled feeding
EUROPE [email protected]
USA [email protected] ORDERING Leasing option available
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The Company
PRODUCT PORTFOLIOSystems The BioLector® microbioreactor is a unique high-throughput fermentation system. In up to 48 parallel cultures the es-sential fermentation parameters such as biomass concentration, pH and DO as well as fluorescent proteins or subst-rates can be all monitored online. The advanced BioLector® Pro technology is using proprietary microtiter plates with an integrated microfluidic chip. By using the microfluidic technology the system continuously controls the pH of each culture individually as well as the feeding for fed-batch cultivations. The BioLector® microbioreactors are established systems for bacterial, yeast, fungi, plant and insect cells. All systems are suitable for aerobic, microaerophilic and strict anaerobic cultivations.
Disposables m2p-labs provides worldwide unique microtiter plates with improved oxygen transfer and excellent mixing pro-perties. Due to its design, the FlowerPlate® supplies microbial cultures even with high oxygen demands with a sufficient amount of oxygen. In addition, the proprietary microfluidic plate uses 16 donor wells for online feeding and pH control. The round well plate delivers moderate oxygen transfer for organisms with lower demand in oxygen or organisms sensitive to shear stress. All plates are available with different optical sensors for different applications.
Automation The RoboLector® provides an unique automated cultivation platform combining the high-throughput fermentation and the online monitoring capability of the BioLector® with the very accurate and reproducible pipetting of a liquid handling robot. The system is used for media preparations, automated sampling and dosing steps, inductions and fed-batch processing.
EUROPE
m2p-labs GmbHArnold-Sommerfeld-Ring 252499 BaesweilerGermanyPhone +49-2401-805-330Fax [email protected]
USA
m2p-labs, Inc.400 Oser Ave, Suite 1650Hauppauge, NY 11788USAPhone +1-631-501-1878Fax [email protected]
m2p-labs is a worldwide leading supplier of microbioreactors.
The company focuses on microreaction and automated solutions for screening and bioprocess development. The microfermentation technology enables customers to conduct experiments with greater efficiency, better quality and lower cost than in any other cultivation platform. More knowledge from small scale leads to more rational and reliable decisions in the development of bioprocesses.
www.m2p-labs.com
Information is subject to change. m2p-labs, BioLector, FlowerPlate and RoboLector are registered trademarks of m2p-labs GmbH, Germany.
![BioLector I 48 Parallel Microbioreactors - m2p-labs · BioLector® I 48 Parallel Microbioreactors ... pH value [-] Multiparameter-Monitoring in the FlowerPlate ... and bioprocess](https://img.pdfslide.net/doc/110x75/5b3e03327f8b9a895a8e6bf3/biolector-i-48-parallel-microbioreactors-m2p-labs-biolector-i-48-parallel.jpg)
