Multi-axis robots achieve scale-up in cell culture production by mimicking human movements and automating bench scale processes, rather than using larger bioreactors
Automation of cell culture techniques in the life science industries is increasing as pharmaceutical and biotech companies realise the advantages achievable through the use of multi-axis robots to ensure precise control and reliable, consistent performance of many complex processes.
The Automation Partnership (TAP) designs, develops, manufactures, and integrates automation solutions for the life science industries; producing unique and technically advanced solutions to many demanding applications. Working together with Stäubli, the leading manufacture of precision industrial robots, many manual, laboratory based processes have been automated, reducing contamination and batch to batch variation as well as permitting the scaling-up of cell production volumes without problem.
TAP was formed in 1988 as the Automation Division of The Technology Partnership, a start-up venture drawing on the resources of nearby Cambridge University. In 1995 TAP became an independent company recognised as a specialist in automation solutions for sample management and handling, liquid handling, high throughput screening and cell culture systems.
TAP's involvement in cell culture started when an existing customer wanted to automate a manual laboratory-based process for the production of hormones.
TAP devised a solution, which was built around a Stäubli RX60 robot that replicated the smoothness of handling and dexterity of movement of the human arm.
Richard Archer, TAP's CEO, little thought at the time that this would be the start of a new ongoing activity.
"Our customer was very specific on the performance criteria of this automated system, we regarded our solution as being uniquely suited to these requirements and doubted that there could be a market for this type of dedicated automation." The system proved so successful that the customer installed four manufacturing lines.
Word spread across the scientific sector of the success of this automated cell growth system and soon TAP was receiving interest from other manufacturers.
One of the first enquirers was US pharmaceutical company Merck.
Merck wanted to automate the manufacture of its new Varicella (chicken pox) vaccine and scale-up production volumes in response to a rapidly growing demand.
Traditionally, scaling-up production meant transferring the process from small culture vessels into large bioreactors - a technically difficult and time-consuming development with no guarantee of success.
TAP believed that it would be possible to automate the bench-scale process, avoiding the need for risky technical changes while achieving the required production rate and consistent level of quality.
The end result was the robot based automated cell culture system now branded Cellmate.
Positioned at the centre of each Cellmate system in a clean (class 100) laminar flow cabinet, a Stäubli RX 60CR cleanroom robot replicates precisely every step of the previously manual process, mimicking exactly each movement just as it would be performed by the operator at the lab bench. The system automates all operations eg, cell seeding, media changes, bottle gassing, and cell sheet rinsing, and only requires the operator to load the infeed conveyor and unload the bottles or flasks after processing.
It is capable of handling cells in both roller bottles and T-flasks up to volumes of 1000 bottles per day.
Smoothness of movement is a vital factor when dealing with the fragile cells, any jerking or slightly rough handling can cause cell damage and halt the cell growth process. The RX range of robots is ideal for such demanding applications, the unique JCS gear reduction system provides zero backlash and precision torque control allowing power to be gradually applied to each joint as required.
The cleanroom characteristics of the robot fall well within the specified class100 range, achieving class 1 cleanroom levels.
A smooth wipeable outer sealed surface to the robot aids cleaning between processing different cell types.
The PC controlled RX60 arm can be easily reprogrammed or modified to suit any specific cell line or process.
All process variables are stored on the PC such as volumes, temperatures and timings as well as the specific robot movements.
Stäubli and TAP have jointly developed the simple control interface, which allows users to alter parameters after the minimum of training.
The robot arm picks up the vessel, bottle or flask, and smoothly moves to a succession of workstations within the cabinet in accordance with the processing instructions that have been selected on the PC.
On completion the vessel is placed on the output conveyor.
Robotic processing has also dramatically reduced contamination levels: a frequency level of 1 in 50 million is regularly achieved compared to typically 1 in 20 by manual handling.
The Cellmate system was developed from initial designs to a fully operational system in nine months.
Merck was impressed, and hase now installed 11 systems working on vaccine production and cell culture.
There are currently Cellmate systems operating in 65 locations around the world.
Demand for Cellmate is set to rise further as genetic engineering advancements and the possibility of using embryonic stem cells as the feedstock to grow many types of human cells call for precise and reliable automation production processes.
Both TAP with the Cellmate system and Stäubli with the RX range of robots are ready to respond to these challenges.
