Bioreactors

Bioreactor Systems
For Rapid Bioprocess Development

www.helgroup.com
 BioXplorer 100
Compact screening with high information content

Based on an 8 reactor block, with a maximum value of

100 ml or 200 ml, the BioXplorer 100 is a high throughput, Block for the 100 range reactors
bioprocess screening system. Designed for working volumes
from just ml in blocks of 8 individually controlled bioreactors.
Blocks can be combined to give even larger number of
parallel reactors.

|F  ully automated, high information content screening tool

ideal for DOE studies, with all the typical sensors and
controls
| Most compact system for optimised use of bench space
| Highly cost effective system for scalable, rapid, high
throughput bioprocessing
| Ideal for cell line/strain screening, media optimisation
and small scale process development
| Suitable for robotic integration

Typical BioXplorer 100 configuration

8 reactor block can also fit on liquid handling robots

for automated sampling and downstream processing

Bioreactors
compatible with
the BioXplorer
100 System

Bioreactor
100 ml 200 ml 200 ml
Volumes

Working 20 ml 20 ml 20 ml
8 parallel reactors totally independent in temperature, stirring and Volumes to 70 ml to 150 ml to 150 ml
all other process conditions. Multiple blocks can be combined

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BioXplorer 400
Flexible, high data content optimisation

Based on a 4 reactor block, the BioXplorer 400

provides the ideal platform for bioprocess Block for the 400 range reactors
development and optimisation using 4 or 8
reactors in parallel with fermentation working
volumes up to 400 ml.

|M  ost versatile bioprocessing platform for

development and optimisation
| High information content and excellent
scalability to large scale bioreactors
| Reduce media costs and optimise the use
of bench space

Typical BioXplorer 400 configuration

Four different size reactors interchangeable on the same

reactor block. Multiple blocks can be combined

Bioreactors
compatible with
the BioXplorer
400 System

Bioreactor
100 ml 200 ml 500 ml 200 ml 500 ml
Volumes

Working 20 ml 20 ml 60 ml 20 ml 60 ml
8 parallel reactors (using 2 blocks) totally independent in Volumes to 70 ml to 150 ml to 400 ml to 150 ml to 400 ml
temperature, stirring and all other process conditions

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 Elevated Press
BioXplorer 100P - 400P
Parallel high pressure mini bioreactors
200 ml to 1 L systems Bioreactors
compatible with
the BioXplorer
100P - 400P
System

Bioreactor
200 ml 500 ml 1000 ml
Volumes

4 x 500 ml high functionality reactors rated to 10 bar, on a Working 20 ml 60 ml 60 ml

linear (AutoMATE) platform. Simpler reactor configurations Volumes to 150 ml to 400 ml to 700 ml
can be fitted on compact reactor blocks

BioXplorer 5000P
Designs for larger 1 to 20 L systems
|F  loor standing frame
| Easy bioreactor manipulation
| Built in Steam in Place (SIP) operation

Easy to open top and Range of interchangeable 2 L Bioreactor rated to 10 bar with SIP,
change internals reactors available up to 20 L with custom configurations

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sure BioXplorer
Benefits Of Pressure
Elevated gas pressure increases the solubility of gases and can produce
commercial benefits in both bacterial and cell culture applications.
The BioXplorer P range can operate up to 10 bar providing benefits which include:
| Increased gas fermentation rate
| Enhanced gas transfer rate (beyond high KLa limits)
| Replication of pressure effects of large scale operations
| Reduced dependence on sparging/agitation for gas availability
Highly controlled pressure regulation and monitoring in each reactor is provided
additional to normal controls such as DO, pH, OD, liquid dosing etc.
A range of features dealing with operator safety are included as standard.

Gas Transfer Rate of Oxygen into Autotrophic Growth and Production of Isopropanol
Water at different Pressures Capriavidus Necator pEG7d at High Pressures

5
4.5

4
1.8 4
OD600 , Isopropanol (g/L)
Max. Oxygen Flux (g/l/min)

3.5
1.6
3 1.4

Pressure (bar)
3
2.5 1.2
1
2
2
0.8
1.5
0.6
1 1
0.4
0.5 0.2

0 0 0
0 1.5 2 2.5 3 3.5 4 0 5 10 15 20 25 30 35

Pressure (bar) Time (h)

500 ml reactor stirred at 1500 rpm, as pressure is Growth was sustained during the whole cultivation.
increased in steps from 1 bar to 4 bar Specific rate of isopropanol was maintained at a high level to
the end. Experiments in 500 ml stirred bioreactors with control
and monitoring of pH, DO and optical density.
(REF: Guillouet, LISPB, France, 2018)

Key Features P Range

| Independently controlled single or multiple parallel bioreactors
| Range of stainless steel pressure vessels available, rated up to 10 bar (145 psi) with
working volumes starting from 20 ml
| Automated pressure monitoring and control of each bioreactor
| Highly instrumented bioreactors with pressure rated probes, feeds and filters
| Option of complex automated gas feed strategies with feedback to off gas analysis
systems allowing real time response to changes in head-space gas composition
| Elevated pressure sampling system for convenient sampling throughout the process
| System capable of temperatures from ambient to 225 oC allowing higher temperature
applications, Steam in Place (SIP) option and downstream processing normally
requiring a dedicated chemical process development system
|F  ull suite of safety features

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 BioXplorer Accessories
Compact screening with high information content

Software Control
Class leading powerful software with a range of
add on modules. All BioXplorer parameters can be
monitored/controlled including:
|  emperature
T
| Gas feeds, flow and mix
| pH
| Dissolved oxygen
| Redox
| Stirrer speed
| Torque (for viscosity indication)
| Pressure
| Liquid feed rates
| Antifoam and level detection

Gas Feeds
|C  hoose from simple or more sophisticated gas
flow control regimes
| Each bioreactor can be configured with single or
multiple mass flow controllers
| For microbial fermentations, automatic oxygen
enrichment is possible if an air and oxygen (or
enriched oxygen) source is supplied – the controller
can be set to maintain a chosen dissolved oxygen
(DO) value by altering the amount of supplied gas
| For cell culture applications CO2 can be used for
pH control
|R atios of several gases can be mixed and regulated
with online feedback from off gas analytics

Liquid Feeds
|C  hoice of liquid feeds for standard and pressure applications
| Highly linear peristaltic pump drives are integrated into
standard heads 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 as needed
| Syringe pumps and high pressure pumps are also available

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Magnetically Suspended Stirring
|  EL’s proprietary design is recommended for reactors up to 500 ml
H
| Ideally suited to small bioreactors with proven performance
| No shaft seal or moving parts: no sterility issues
| Excellent magnetic coupling
| Range of stirrer designs (marine, rushton, etc)
| Speed 300 rpm to 1500 rpm or 30 rpm to 200 rpm

Overhead Stirring
|O  verhead stirring is offered on vessels from 300 ml upwards
and is commonly used for larger bench-scale reactors
| For pressure applications special magnetic drives are used

pH, Dissolved Oxygen and Redox

A complete range of bioprocess probes are available to cater for different
conditions, reactor sizes and applications. All probes are integrated into
software to allow automated monitoring and feedback loops.

Off Gas Analysis

Tandem off-gas analysis units as an on-line tool 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.

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.

Robot Integration
Robotic sampling and work-up as required.

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Specifications
BioXplorer 100 / P BioXplorer 400 / P BioXplorer 5000P
Parallel Bioreactors 8 or more 4 or more 2 or more
Vessels Glass Glass Glass
Stainless Steel Stainless Steel Stainless Steel
Working Volumes 20 ml to 150 ml 20 ml to 150 ml 20 ml to 15 L
60 ml to 700 ml
Stirring Speed 250 rpm to 1500 rpm* 250 rpm to 1500 rpm* 50 rpm to 1500 rpm*
Impellers Rushton Rushton Rushton
Marine Marine Marine
Pitched Pitched Pitched
Stirring Drive Magnetic drive Magnetic drive Overhead drive
Overhead drive
Temp. Range -20 oC to 200 oC** -20 oC to 200 oC** -20 oC to 225 oC**
Temp. Control Integrated, individual Integrated, individual Heated jacket
electrical heating in the block, electrical heating in the block, Circulator
software controlled software controlled
Applications Mammalian Mammalian Mammalian
Microbial Microbial Microbial
Gas Fermentation Gas Fermentation Gas Fermentation
pH Control Acid/base liquid feed; Acid/base liquid feed; Acid/base liquid feed
Gas addition Gas addition
Liquid Feeds Optional anti-foam; Optional anti-foam; Optional anti-foam;
substrate feeds substrate feeds substrate feeds
OD Measurement Optional Optional Optional
Gas Mixing Air, H2, N2, O2, CO, CH4 and CO2 Air, H2, N2, O2, CO, CH4 and CO2 Air, H2, N2, O2, CO, CH4 and CO2
Max Pressure Up to 10 bar with stainless Up to 10 bar with stainless Atmospheric - 10 bar
steel vessels steel vessels

*Speeds depend on stirrer drive, media properties and aeration rate.

**Sub-ambient cooling requires optional cooling module.

About HEL
HEL is an international company that specialises in chemical reactors, bioreactors and related data/
logging 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

HEL Ltd // UK e: [email protected] t: +44 20 8736 0640

HEL Inc // US e: [email protected] t: +1 609 912 1551
HEL China // Beijing e: [email protected] t: +86 10 8210 1033
HEL Germany // Hamburg e: [email protected] t: +44 20 8736 0640
HEL India // Thane e: [email protected] t: +91 22 4153 3317
HEL Italia // Milan e: [email protected] t: +44 20 8736 0640
HEL Russia // Moscow e: [email protected] t: +44 20 8736 0640

Design: www.hashtagprcompany.com www.helgroup.com