Multiplate bioreactor for cell-based product manufacturing

Features and Benefits

• USP Class VI certified materials
• Designed for adherent cell culture applications
• Treatment for cells adherence
• Single-use closed bioreactor, from vessel to sensors, reduces risk of contamination
• 2-D multiplate design allows easy adaptation from traditional multitray systems
• Integrated,disposable pH DO probes
• Real-time control and monitoring ensures reproducibility and traceability
• Reduced operations results in process simplification, flexibility, and assurance

The Xpansion multiplate bioreactor is part of the Pall Life Sciences’ single-use bioreactor family, designed for shear-sensitive adherent cell applications, such as cultivation of stem cells.

The Xpansion multiplate bioreactor was developed for safe, large-scale production of traditional 2-D cell cultures.The multiplate structure is comprised of a large cell growth surface area (up to 122,400 cm²), while the compact design enables the elimination of the gas phase between the plates. This gas phase is replaced by an automatically controlled aeration system which provides advanced gas diffusion. Control is automatic via disposable pH and dissolved oxygen (DO) sensors. Temperature monitoring and agitation control are also included. Xpansion bioreactors offer the capability of monitoring cell morphology and density through the use of an optional digital holographic microscope.

Xpansion System Components

The Xpansion system includes a single-use bioreactor, docking station and a controller.

Single-Use Bioreactor with Stacked Multiplate Design

Comprised of stacked hydrophilized polystyrene radial plates, the Xpansion bioreactor is designed to promote cell growth on the top of each plate; each plate has a hole in the center. The stacking of these plates forms the central column which allows circulation of the medium in the bioreactor and gas exchange.

The plates are covered by an outer tube, a head plate on the top and a base plate on the bottom. On the head plate, there are:

• Six sensor connectors: pH, DO, and four optional sensors
• Three viewing windows for use with optional holographic microscope
• Two vent filters
• Two gas filters (in and out) for aeration system
• One thermowell port
• One sampling port

In the bottom side of the bioreactor, there are:

• Two fluid operation ports (e.g., inoculation, harvest, etc.)
• One magnetic impeller

An Xpansion Plate

  The Xpansion Multiplate Bioreactor

Materials

1	Gas lines (in & out)	C-Flex* tubing and silicone 3/16 in. ID, 0.2 μm hydrophobic filters (PTFE, polyester, polypropylene)
2	Vent.1	C-Flex 3/16 in. ID, 2 0.2 μm hydrophobic filters (PTFE,polyester, polypropylene)
3	Sampling port	C-Flex 3/16 in. ID with needleless connector for sampling with luer syringe + oneway valve
4	Top part	Clear polystyrene
5	Cell surface plates	Cell culture plasma-treated clear polystyrene
6	Aeration support	Polypropylene + polycarbonate
7	Aeration tubing	Silicone 0.58 in. ID x 0.77 in. OD
8	Outer tube	Polyvinyl chloride
9	Stirrer cover	Clear polystyrene
10	Impeller	Ultra-high-molecular-weight polyethylene
11	Bearing	Polyether ether ketone
12	Bottom part	Clear polystyrene
13	Liquid in/out tubing	C-Flex Clear 374 Tubing 3/8 in. ID, CPC MPC male connector, 0.2 μm hydrophobic filters
	Sealing material	Resin

Docking Station

The bioreactor docks to a station that includes a magnetic drive stirring unit powering the magnetic impeller.

Control of agitation speed is integrated in the controller. The setpoint is defined via the screen on the front side of the controller.

Controller

The controller has measurement/control hardware and a gassing system with a digital control.

Features of the Xpansion controller include:

• Graphic user interface with color display and touch screen operation with Administrator and Operator security levels
• Integrated transmitters for temperature, disposable DO and pH sensors
• Integrated control loops for DO and pH
• Agitation control (speed range from 5 to 250 rpm)
• Temperature monitoring
• DO and pH sensor patches arrive precalibrated; data are transferred via a USB key to the controller
• In-process DO and pH can be recalibrated
• Trend display for up to four process values (pH, DO, T, gas flow rate)

Controller Gas Module
The controller is connected to the user’s gas supply line. Its “gas outlet” is connected to the “gas in” filter of the bioreactor. Gas composition to be injected in the bioreactor is regulated by controller solenoid gas valves. The flow rate of the mixed gas is adjusted by a massflow controller (0-200 mL/min). The controller gas module contains:

• One gas diffuser outlet
• Four solenoid valves of Air, N₂, O₂, and CO₂
• One Mass Flow Controller for mixed gas flow control

Data Management

The Xpansion system has one ethernet port for data communication/ acquisition. It can be linked to egraph (optional software and computer provided by Pall Life Sciences). egraph is installed on a host PC and provides data acquisition for all process values.

Xpansion Controller and Docking Station

Controller

Height	50 cm (19.7 in.)
Depth	40 cm (15.7 in.)
Width	25 cm (9.8 in.)
Weight	15 kg (33 lbs.)
Power supply	100 – 240 VAC, 50 – 60 Hz
Interface	Ethernet USB host
Stirrer speed	5 – 250 rpm
Integrated measurement module	Disposable DO sensor Disposable pH sensor Temperature
One point recalibration function	Disposable DO sensor Disposable pH sensor
Gas options	O2 N2 CO2 Air
Temperature monitoring	0 – 50 ºC (32 – 122 ºF)

Gas Requirements

Gases	Application	Specification
Air	pH control	Compressed air – medical grade Outlet pressure between 1 and 2 bars (14.5 – 30 PSI) 6 mm Festo connectors
CO2	pH control	Pure CO2 Outlet pressure equivalent to air pressure 6 mm Festo connectors
Oxygen	DO control	Medical grade oxygen Outlet pressure equivalent to air pressure 6 mm Festo connectors
Nitrogen (optional)	DO control	Medical grade nitrogen Outlet pressure equivalent to air pressure 6 mm Festo connectors