HEL Xplorer Bioreactor System - Tablazat.hu · transfer to an autoclave. The operating range of the...

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HEL Xplorer Bioreactor SystemFor Parallel Bioprocessing

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The Parallel Screening Platform for Rapid Bioprocess Development

The Xplorer HT

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.

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).

All bioreactors are fully interchangeable and use the same BioFRAME.

Xplorer BioFRAME

Zone Compatibility

InterchangeabilityFull Software Control All parameters can be monitored/controlled including:| Temperature | Gas feeds, flow and mix| pH | Dissolved oxygen| Stirrer speed | Torque (for viscosity indication) | Pressure| Liquid feed rates | Antifoam and level detection

Xplorer HT4

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.

Built to Budget

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Key Features| Bench top system (74(H) x 65(W) x 56(D) cm)| 4 or 8 stirred bioreactors with minimum working

volume of 20 ml (and maximum up to 2.6 L)| Independent pH, DO, stirring and temperature

control in each vessel| Minimal media consumption| Scaleable results| Batch, fed batch and continuous processing for

bacteria, cells and yeasts| Fully autoclavable bioreactors| Easy to use, requiring minimal training| Easy to service and maintain| Systems tailored to specific applications| Flexibility (system can be configured to

simultaneously run bio processes with very different parameters or even to host different types of vessel)

| Real time data analysis and logging

For process control probes including temperature, DO, pH, OD, cell density and viability.

Rotameters or mass flow controllers for gas supply and control.

Gas Flow Control

Multiple Sensors

Efficient Condenser Units

Precise Temperature Control

Peltier cooled exhaust condensers without liquid coolant.

Temperature control with integrated heating/cooling cells (-20 °C to +225 °C).

Precise variable speed pumps provide liquid addition options for automatic acid-base corrections, substrate addition, antifoam agent addition, etc., according to application.

Liquid Flow Control

Xplorer HT8

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Proven, scalable performance using 100 ml and 1.5 L reactors. Above panel demonstrates values across reactors for biomass (left) and oxygen transfer (right)


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

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.

Vessels

Scalability


These reactors also lend themselves to processes at elevated pressure, for example in biofuel synthesis. Probes and lids are interchangeable with glass reactors

The Xplorer HT unit has integrated steam in place options compatible with stainless steel Xplorer bioreactors. This allows a convenient and efficient way of sterilizing bioreactors without the need to transfer to an autoclave.

The operating range of the Xplorer HT is typically ambient to 225 °C (can be expanded to cool down to achieve sub-ambient temperatures). The individual temperature control in each reactor zone is accurate to 0.1 °C. Heating/cooling is applied uniformly around the complete bioreactor for fast and accurate control. The sub-ambient operation of each reactor is made possible through the optional circulation of chilled water or oil.

Long term sterility is important in all aspects of the design. All reactors are easy to disconnect and re-assemble. The top plates and fittings are made from 316 stainless steel and include self-sealing septa. Each complete bioreactor assembly can be autoclaved. Metal trays allow easier loading and transfer of multiple bioreactors to and from the autoclave. Stainless steel vessels can be sterilised in situ due to the Xplorer’s heating power up to 225 °C.

Steam in Place

Temperature Control

Sterility

Aluminium heating/cooling block adapter inside Xplorer HT8


Suspended stirrer design is effective in yielding higher KLa values which can be controlled by changing aeration rates and stirrer speeds (E.coli TOP 10 pQR239)

The XplorerHT offers a choice of stirring systems depending on the size of vessel and the application.

Magnetically suspended stirring| HEL’s proprietary design is recommended for

reactors up to 500 ml| 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 50 rpm to 1500 rpm| Custom designed, scaled stirrers | Range of impeller designs| Single motor/controller design allows:

- Easy to fit and vibration free - Baffles to ensure effective mixing

Agitation: Overhead stirring| Overhead stirring is offered on vessels from

300 ml upwards and is commonly used for larger bench-scale reactors

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.

Stirring

Liquid Feeds

Stirrer Speed (rpm)

500 1000 1500 2000 25000.02

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kLa

(s-1

)

A more compact peristaltic/syringe-based design is also available


For conventional microbial applications, peristaltic pumps are used to add acid/base, providing control to better than 0.05 pH units using an adaptive control method. Single or bidirectional control may be selected. The software records (and displays) the total amount of acid or base consumed. In other applications, such as cell cultures, pH is controlled by gas (CO2) blending.

The Xplorer HT offers a range of simple and more sophisticated gas flow control regimes, from simple gas addition, to gas blending and mixing. Each bioreactor can be configured with single or multiple rotameters and/or 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. In the case of cell culture applications, 2, 3 or 4 gases can be blended including CO2 for pH control. Gases suited to biofuel applications can also be blended using the same method. Different spargers are available to meet specific requirements.

pH Control

Aeration and DO Control

pH calibration with WinBIO software

Multiple mass flow controller unit (~ 23.4 (L) x 11.6 (W) x 7.2 (H) cm)

Example of recipe/step planning


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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

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.

Foam Level Detection

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.

BioVIS: Real-Time Cell Density and Biomass Monitoring

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

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.

Online Off Gas Analysis and RQ Measurement

Case Studies: Escherichia Coli Process DevelopmentThe 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.

Time/ hours

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RQ = CER / OUR

Point of Phosphate depletion

O2

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O2 Value

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CO2 %


Each Xplorer HT system comes with the state-of-the-art WinBIO software. In keeping with the flexibility of the hardware a number of control and data management options are possible, including DOE software integration and OPC client connectivity.Each reactor is displayed in its own window, showing real time process parameters and providing functions for sensor calibration, process control, experiment profiling, recipe, data logging and experiment review. New features can be easily added to include controls for specific needs or analytical process instrumentation.

Greater ControlKey Software Features| Control and monitoring of unlimited parameters in

each bioreactor| Quick overview of all bioreactors or focus on a

specific reactor for detailed analysis| Unlimited step recipe planning. The plan can be

changed online at any time without process interruption

| Start reactors individually or simultaneously| Decide on how the system should respond to

bioprocess conditions, including time or multiple event-based control

| Link and cascade any number of process variables to perform sophisticated control loops and event management strategies

| Manage which parameters are logged and recorded with customised tabular and graphical displays

| Develop, design and create process recipes anywhere with the “simulator” mode. Save and load onto the system when needed

The mimic screen gives an interactive graphic display of the entire system process.

Tabular and graphical displays of real time data

Unlimited step recipe planning. The plan can be changed online at any time without process interruption

Export data functions and integration with in-house electronic lab notebooks and record keeping systems

Decide on how the system should respond to bioprocess conditions, including time or multiple event-based control


24 bioreactors integrated with Hamilton Star Liquid Handling Workstation

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

Configured to suit your Application

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.

Integration with Automated Liquid-Handlers


Larger bench scale bioreactors up to 3 L volume can be operated from the same platform as the miniature type. The larger volumes can be selected in preference to or as well-as the miniature size.

Applications include:| High throughput screening| Media optimization and development| Process optimization and development| Process scale up and scale down| Batch, fed-batch, and continuous

cultivation experiments| Process analytical technology (PAT)| Microbial or cell culture cultivation

Reactors up to 3 L - Xplorer N

All the features described can equally be supplied in a single reactor platform, with the full range of reactors available, to use interchangeably. The control unit for a single reactor, has a wide choice of reactor sizes. All the features of the Xplorer HT are available on this platform, providing lower price entry solutions.

Single Reactor Platform

www.helgroup.comDesign: www.blitzbranding.co.uk

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

About HELHEL 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 chemistsQuality - underpinned by ISO9001 certification for over 16 yearsService - choice of service contracts backed by an established culture of unmatched client supportRange 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 Xplorer Bioreactor System - Tablazat.hu · transfer to an autoclave. The operating range of the...

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