In today’s biotechnology landscape, to be competitive, meet regulations, and achieve market demands, “we must apply Bioprocessing 4.0,” said Igor Fisch, PhD, CEO, Selexis. In fact, in the last decade, “Selexis has evolved from cloning by limiting dilution to automated cell selection to nanofluidic chips and from monoclonality assessment by statistical calculation to proprietary bioinformatic analysis,” he added.
Single-use processing systems are an expanding part of the biomanufacturing world; as such, they are a major component of Bioprocessing 4.0. “At Selexis, we use single use throughout our cell line development workflow. Currently, we have incorporated single-use automated bioprocessing systems such as ambr® and the Beacon® optofluidic platform for accelerated cell line development. By using these systems and optimizing our parameters, we were able to achieve high titers in shake flasks. Additionally, the Beacon systems integrate miniaturized cell culture with high-throughput liquid handling automation and cell imaging. This allows us to control, adjust, and monitor programs at the same time,” noted Fisch.
He argued that the company’s approach to innovation is a combination of pure science and technological advances (developed in-house and externally). As an example, “we can rescue a drug development program by manufacturing a cell line producing a difficult-to-express protein in as little as 14 weeks. Without the application of Bioprocessing 4.0, reaching Selexis targets in terms of cell line productivity, growth performances, and product quality, would have been much more challenging,” he said.
Indeed, manual-limiting dilution, cell counting, and SDS-PAGE are fastidious and subjected to additional cross-verification. The implementation of automated clone selection, automated cell growth tracking, and automated microcapillary electrophoresis-SDS ensures that the selection of high-producing clones meets product quality requirements and reduced timelines.
Selexis is now able to achieve an accelerated stable production-ready research cell bank program in eight to 14 weeks, pointed out Fisch.
“Central to this timeline are proprietary genetic elements that enable us to reduce the number of clones to screen and therefore the RCB development timeline. We have further developed cell secretion assays using a high-throughput imager system to predict the proportion of high-producing cells within a heterogeneous cell population at a very early stage, which is an important tool to make the best decision at the right time and more quickly,” he said. “Finally, automated clone selection based on fluorescence intensity followed by rapid ranking of the best clones using high-throughput technologies and cell growth tracking have been optimized. This allows us to identify high-producing and stable cell clones in a very short time.”