Accelerating biopharmaceutical discovery with single-cell analysis

This paid-for advertorial by Sphere Fluidics appeared in DDW Volume 25 – Issue 2, Spring 2024. Sphere Fluidics discusses how picodroplet microfluidic technology and automated single-cell analysis can help overcome barriers to accelerating biopharmaceutical discovery and cell line development workflows. Challenges in cell line development Biopharmaceutical development is a time-consuming and costly process. As a result, the pharmaceutical industry is increasingly under pressure to streamline therapeutic discovery and associated cell line development processes. The early selection of individual high-producing cells from a large cell population is critical to optimising the success and efficiency of biopharmaceutical production. However, generating suitable cell lines for production can be challenging due to numerous factors that influence cell line quality and performance, and growing regulatory requirements relating to evidence of monoclonality. Limiting dilution is a traditional method for single-cell cloning, where cells are diluted to a low concentration, plated out and allowed to proliferate. Whilst being a straightforward cloning method, limiting dilution is slow, low-throughput, prone to contamination and expensive. As such, there is an urgent need for high-throughput technologies that harness automation to optimise and streamline cell line development workflows, to ensure the most valuable cells can be found, analysed and isolated, with ease and speed. The automated solution using a picodroplet microfluidic platform Picodroplet technology is a unique and invaluable ultra-miniaturised approach to single-cell analysis, enabling high-throughput, rapid, yet gentle, cell processing. Each picodroplet is an aqueous droplet containing a single cell and assay reagents encapsulated in a biocompatible carrier oil, which acts as an independent picolitre sized reaction vessel. There are many benefits of working in picodroplets. Firstly, each picodroplet is a self-contained reaction vessel enabling detection of both secreted molecules from live cells and cell surface markers. Secondly, working at highly concentrated picolitre volumes increases detection sensitivity and significantly lowers operating costs. And, lastly, whilst cells are encapsulated within a droplet they are protected from the sheer forces that they would experience during processing if they were in free suspension, ensuring high viability of the cells at the end of the process. Sphere Fluidics has leveraged its microfluidics expertise and patented picodroplet technology to develop Cyto-Mine – an integrated single cell analysis and monoclonality assurance platform that facilitates high-throughput single-cell screening, sorting, dispensing, imaging and clone verification within one automated platform. Cyto-Mine eliminates the need for laborious and time-consuming approaches such as limiting dilution, and can automatically screen up to 40 million cells in a matter of hours, compared with 10,000 typically achieved using multi-step manual techniques. This powerful and sensitive approach provides a high-throughput workflow that enables screening of large starting populations of cells and direct dispensing of your chosen positive hits into individual wells of a microplate, dramatically shortening the time required to get to single clones whilst simultaneously reducing the cost of the cell line development process.