October 28, 2019 PAP-Q3-19-CL-016
The accurate and reliable measurement of protein titer is essential for ensuring optimal cell culture performance for the production of many biologics. The ability to reliably monitor protein titer in real time throughout a bioprocess allows operators to rapidly adjust the process conditions for maximum protein output while minimizing the process time. Quick access to titer data also enables earlier decisions regarding preparation of downstream purification systems (e.g., protein A), further reducing the production timeline.
Real-time monitoring of protein titer facilitates the adoption of continuous bioprocessing.
IDEX Health & Science has developed the first fit-for-purpose chromatographic device for rapid, automated at-line measurement of antibody titers from stirred bioreactors using an aseptic sampling device. The Tridex™ Protein Analyzer is compact and easy to use. The unique trap-and-elute technique, which quantifies the amount of IgG in a cell-free sample, delivers accurate titer measurements over a dynamic range of 0.1–10 g/L with minimal sample manipulation. The sample flowpath is completely enclosed, lending itself to the requirements of single use.
As a result, the Tridex Analyzer is a complete solution for at-line titer monitoring in a bioprocess environment that provides actionable data quickly, enabling critical decisions to be made in real time.
High-performance liquid chromatography (HPLC) is the current standard technique for determining protein titer. Performance of the Tridex Protein Analyzer has been shown to provide at-line results that directly correlate to offline HPLC methodology. In-house1 and field testing2-–4 have shown that the system provides results within +10% of those obtained using offline HPLC over the full titer range. In one example, excellent intra-assay precision (CV <3%) was demonstrated for both off-line and at-line measurements obtained with the Tridex Analyzer and a commercial protein A HPLC system.1 Measurement data were also shown to be unaffected by changing BSA levels up to 2.5% (v/v).
Unlike HPLC, for which specialized chromatographic expertise and experience are necessary, no scientific background is required to operate the Tridex Protein Analyzer. No method development is required, nor are sample dilutions or other sample manipulation steps, such as centrifugation. Results are provided within five minutes of sample injection, and the system is immediately ready for the next sample following completion of an analysis
The Tridex Protein Analyzer is designed for simple operation and maintenance. Protein titer is determined in four easy steps: selection of a calibration curve and entry of sample information, sample loading, running the sample (push-button start) and review of the results. The software is easy to navigate and consists of four user-friendly screens.
The overall footprint is quite small — just slightly larger than a legal-sized piece of paper — and the system weighs only about 20 pounds, so it is quite portable and easy to maneuver. The Tridex Analyzer is also easy to install and typically can be up and running within one afternoon.
IDEX Health & Science, with extensive experience in the development of advanced optofluidic technologies for the life sciences, recognizes the increasing pressure that biopharma companies are facing to reduce cost and increase biomanufacturing productivity and the role that automation and process analytical technologies will play going forward.
We have applied our engineering expertise to the design of a real-time protein titer determination with the Industrial Internet of Things (IIoT) and Industry 4.0 in mind. The Tridex Analyzer incorporates key capabilities for interconnectivity with internal networks comprising commonly used software systems.
Commercial automated sampling systems that pull samples aseptically from bioreactors can also be connected to the Tridex Analyzer via a “trigger” that tells the system to initiate an analysis. While manual operation is available if required, this solution allows for real-time monitoring of protein titer without the need for any human intervention.
Kurt Pickle is the Business Line Leader for the Bioprocess Analytics group within IDEX Health & Science. He has worked at IDEX for over 14 years, where he has held several leadership roles including Business Line Director of Biotech and Vice President of RD&E. Kurt is able to combine technical expertise and deep market understanding to lead teams in developing novel solutions that meet challenging needs in bioprocessing.