Automated Protein Production Technologies


The automation of recombinant protein production enables the rapid and parallel processing of multiple products. Laboratory robotic systems have been developed that deliver a range of automated protein production technologies, including expression screening in both cell‐based and cell‐free systems. Liquid handling robotics are routinely used in the small‐scale purification of proteins in parallel based on affinity capture methods typically on metal chelating matrices. Multidimensional chromatography has also been automated enabling complex protein purification strategies to be carried out with little manual intervention. The increasing use of cell‐based assays in discovery projects has driven the development of dedicated robotic systems for handling the culture of mammalian cells. Critical to the successful implementation of laboratory automation is the development of an information management system to ensure the recording of data and tracking of samples generated during the process of protein production.

Key Concepts:

  • The automation of recombinant protein production enables the rapid and parallel processing of multiple products.

  • Automation can be beneficial in both cost and reproducibility.

  • The automation of liquid handling tasks involving either cells, nucleic acids or protein samples is central to all laboratory robotic systems.

  • Using modular robotics enables workflow changes to be introduced without the need to rebuild a complete system.

  • Managing the increased volume of data arising from automation can be a problem in its own right.

  • The biggest benefits come from integrating automated systems with electronic Laboratory Information Management Systems.

  • Analysis of the large datasets collected can lead to tools that predict how an untested protein will behave.

Keywords: automation; protein production; laboratory information management

Figure 1.

A streamlined protein production workflow.

Figure 2.

A plan layout of the Piccolo cell culture and purification robot showing the major system modules. A rail‐mounted 6‐axis robot transfers 24 micro‐well (CVB) between the liquid handling, incubator and centrifuge modules and retrieves reagents and labware from the storage carousels. E. coli expression strains are grown in CVBs in the incubator units (4 stacks of 16 vessels) and cell density monitored in situ by absorbance. At a pre‐defined cell density cultures are transferred to the liquid handling module and protein expression induced by the addition of IPTG. Following incubation for a user specified period (typically 4–8 h) cells are retrieved by the robot arm from the incubator and returned the liquid handling station for processing. Cells are lysed by the addition of detergent and the lysate cleared by centrifugation in the centrifuge module. Proteins are purified from the supernatant fraction by IMAC on the liquid handling module using a vacuum filtration. Reproduced from Wollerton et al. with permission from Elsevier.

Figure 3.

Schematic flow diagram of ÄKTAxpress automated chromatography system. The system consists of a pump and a series of five multiway valves that control liquid flow through the system. The inlet valve controls sample loading and the selection of chromatography buffers with an in‐line air sensor detecting the end of sample loading and directing the switch to the buffer loading step. Up to five columns can be accommodated in series with in‐line UV detection used to monitor the eluted protein which is automatically transferred to one of five holding loops between purification steps. The outlet valve controls outflow to either the fraction collector or flow through to waste. Reproduced from Bhikhabhai et al. with permission from Elsevier.

Figure 4.

Plan layout of the (PEPP) developed by the Joint Centre for Structural Genomics ( A centrally located articulating robotic arm transports culture flasks between the various modules of the system. SBS‐formatted culture flasks (up to 96 flasks) are seeded with cells grown in suspension in the bioreactors and transferred to the incubators. Transient transfection of cells for protein production is carried out at the transfection station and cells returned to the incubators. After 96 h, medium containing expressed proteins is recovered by low speed centrifugation of the cultures and proteins purified by IMAC using vacuum filtration on the protein purification station. Reproduced with permission from Gonzalez et al. .



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Web Links

Protein information Management System (PiMS); www.pims‐

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Owens, Raymond J, and Diprose, Jonathan(Mar 2011) Automated Protein Production Technologies. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023168]