Full Software Control. All parameters can be ... of reactors, a control unit and software. This can be ..... or analytic
BioReactors
HEL Xplorer Bioreactor System For Parallel Bioprocessing
www.helgroup.com
The Parallel Screening Platform for Rapid Bioprocess Development
The Xplorer HT
Built to Budget
Xplorer BioFRAME
The Xplorer HT is a total solution consisting of reactors, a control unit and software. This can be configured to suit the application and budget, with future expansion if required. A variety of layouts are available from a single bioreactor to 4 or 8 independently controlled reactors with working volumes of 20 ml to 2.6 L.
The BioFRAME houses all the resources needed by the bioreactors. This control unit has expansion slots, to allow the system to accommodate any ongoing developments and to protect investment.
Zone Compatibility The bioreactor zone is compatible with the 4 zone (Xplorer HT4) block, the 8 zone block (Xplorer HT8) and larger bioreactors to 3 L (Xplorer N).
Full Software Control ll parameters can be monitored/controlled A including: | Temperature | Gas feeds, flow and mix | pH | Dissolved oxygen | Stirrer speed | Torque (for viscosity indication) | Pressure | Liquid feed rates | Antifoam and level detection
Interchangeability All bioreactors are fully interchangeable and use the same BioFRAME.
Xplorer HT4
1
> 2
Vessels The Xplorer HT system offers a choice of interchangeable vessels with volumes of 100 ml, 300 ml and 500 ml. To address a range of processing requirements, vessels are available in autoclavable glass and stainless steel versions. The vessels can be configured with different impeller designs and include a stainless steel top plate with ports for: | Flexible stirring motor coupling | Dissolved oxygen sensor port | pH electrode port | Acid and base or antifoam agent addition port | Inoculation port | Inlet gas port – fitted with ring sparger, with a range of configurable options | Outlet gas port – with sterile exhaust gas condenser | Thermowell for PT100 sensor | Sterile sampler assembly | Reactor volumes above 500 ml (up to 3 L) can also be integrated into the same control system
Scalability The key feature of the mini bioreactor design is to ensure the replication of results obtained using larger scale vessels. This is achieved through careful design of vessel geometry, agitation, excellent control of pH and the reliable monitoring of DO.
100
5
80
4 DOT (%) ..
Biomass Concentration (g DCW.L-1)
6
1.5 L
3
60
1.5 L
40
100 mL
100 mL
2
20
1
A
0 0
100
200 Time (min)
300
400
B
0 0
100
200 Time (min)
Proven, scalable performance using 100 ml and 1.5 L reactors. Above panel demonstrates values across reactors for biomass (left) and oxygen transfer (right)
3
> 4
Stirring The XplorerHT offers a choice of stirring systems depending on the size of vessel and the application.
0.12
Magnetically suspended stirring
Agitation: Overhead stirring |O verhead stirring is offered on vessels from 300 ml upwards and is commonly used for larger bench-scale reactors
Liquid Feeds Highly linear peristaltic pump drives are integrated into standard heads, (choice of different sizes) which enable exceptional pH and dosing control as well as a wide operating range. Typically, two to four pumps per reactor are supplied but additional pumps can be added if needed.
A more compact peristaltic/syringe-based design is also available
5
> 6
Foam Level Detection Foam generated in each bioreactor can be controlled by dosing an anti-foam agent, using a peristaltic pump. This can be controlled automatically through feedback from a foam detector, or as a function of time. This is not normally required for reactors below 500 ml.
BioVIS: Real-Time Cell Density and Biomass Monitoring BioVIS allows the online monitoring of cell growth and biomass using optical density, which can reduce or replace the need for online sampling. This feature allows the user to track the growth and understand the processes without taking samples. Viable cell density probes can also be integrated.
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6
4
4
2
2
A
0 0
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200 300 Time (min)
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12 On-line Optical Density
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On-line Optical Density
Off-line Optical Density
14 8
10 8 6 4 2
B
0
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500
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4 6 8 10 Off-line Optical Density
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14
Proven batch to batch reproducibility across multiple reactors in parallel. The left hand graph demonstrates the comparison of offline and on-line growth kinetic profiles. The right hand graph demonstrates the results from 8 separate E.coli fermentations in 100 ml reactors
Online Off Gas Analysis and RQ Measurement As part of the Xplorer system, HEL offers a range of Tandem off-gas analysis units as on-line tools to monitor and control a process continuously. By monitoring the off-gas, the software can automatically calculate the oxygen uptake rate (OUR) of the cultivated cells and the carbon dioxide production rate (CPR) can be measured for micro-organisms. From this data, the respiration quotient (RQ) can be calculated automatically.
Case Studies: Escherichia Coli Process Development The example below shows how the Tandem gas analyzer was used to determine the point of phosphate depletion. There was a sharp fall in carbon dioxide and a rise in oxygen in the exhaust gas, corresponding to a metabolic event
The Tandem provides fine detail on the real-time activity of the organism: the first switch in feed is clearly visible while RQ changes may reflect metabolic changes in carbon and nitrogen substrates. Automating the feed profiles from this information has optimised the process.
O2 Value
CER (mmol L)
CO2 Value
OUR (mmol L) RQ = CER / OUR
60
1.2
1.0
40
0.8
30
0.6
20
0.4
10
0.2
Respiratory Quotient
CER/OUR mmol L -1h-1
CO2 % 50
Point of Phosphate depletion
O2 %
7.00
30.0
5.25
25.0
3.50
20.0
1.75
15.0
0
10.0
O2
CO2 0
0.0 0
1
2
3
Time/ hours
7
> 8
Configured to suit your Application HEL provides preconfigured application packs with a range of options for: | Microbial Cultures (bacteria or yeast) | Anaerobic Cultures | Mammalian Cell Cultures The packs are optimised for: | Vessel design | Agitation speeds and impellor design | Gas management options including multi-gas mixing | Variable gas and liquid flow rates | Sophisticated software control features It is possible to extend the standard packs so that more than one type of application is possible. Customized application packs can also be designed on request with options for: | CO2 sensors | NOx sensors | Fast response DO probes | Viable cell density | Bio-calorimetry
Integration with Automated Liquid-Handlers The Xplorer HT units can be accommodated with deck-based liquid handling systems, to give complete upstream and downstream bioprocessing solutions. Depending on deck size, up to 48 reactors can be integrated with seamless hardware and software integration. Robot-friendly vessel design means that samples can be taken automatically, from any reactor based on one or multiple events.
24 bioreactors integrated with Hamilton Star Liquid Handling Workstation 9
> 10
About HEL HEL is an international company that specialises in chemical reactors, bioreactors and related data logging/automation tools for process R&D in the pharmaceutical, fine chemical, biotechnology and petrochemical industries. Established in 1987 and with clients worldwide our key strengths are: Knowledgeable staff - highly qualified and experienced chemical engineers and chemists Quality - underpinned by ISO9001 certification for over 16 years Service - choice of service contracts backed by an established culture of unmatched client support Range of products - both off-the-shelf and custom designs, manual and fully automated controls, low and high pressure/temperature applications, single and parallel/multi-vessel products
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