Cell line development with the Cyto-Mine®

Scientists at FUJIFILM Diosynth Biotechnologies have transformed their cell line development processes by incorporating Cyto-Mine®, the next-generation single-cell analysis system developed by Sphere Fluidics.

Compared to past workflows, the new procedures are simple and productive. Projects are now able to transition swiftly from the initial transfection phase through to the development of highly productive cell lines within around ten weeks.

Cell line development: Critical objectives and challenges

Specialist contract development and manufacturing organizations (CDMOs) offer technical expertise and capacity in cell line and process development to optimize the production of biological medicines for biotherapeutic manufacturers.

In this commercially competitive industry, CDMOs are under mounting pressure to provide robust and prolific stable cell lines in shorter durations to expedite the transfer of medicinal compounds to clinical research. This must be accomplished without compromising the quality of biological products.

Innovative antibody fragments and bispecific antibodies are challenging to manufacture in stable cell line expression systems at adequate titers for commercial drug research programs and large-scale production compared to conventional monoclonal antibody molecules.

Technologies that offer enhanced predictive screening capabilities and higher throughputs than those conventionally used in cell line development laboratories have been sought after to meet the growing urgency and demand for unique biotherapeutic molecules.

Traditional manual screening approaches, such as colony picking and restricting dilution cloning, are laborious, time-consuming, and limited in terms of the number of cells that can be treated or evaluated in a given time frame.

Industry regulators, such as the Food and Drug Administration (FDA), require evidence of monoclonality regarding cell lines used in the production of biological medicines.

To prevent expensive delays in market authorization and clinical trial programs, manufacturers must demonstrate that each cell line is produced from a single parent cell.

Conventional methods do not allow visualization of individual cells upon initial seeding, making the demonstration of monoclonality difficult or impossible in certain cases.

Cell line development with the Cyto-Mine®

Image Credit: Sphere Fluidics

Cyto-Mine® in practice: Improving efficiency and ensuring quality

Cyto-Mine® is a platform for the single-cell investigation that permits the encapsulation of individual cells inside picolitre-sized aqueous droplets in a biocompatible carrier oil (pico-droplets).

This technique has been used by FUJIFILM Diosynth Biotechnologies to produce a single-step cloning procedure that eliminates bottlenecks in the cell growth process and enhances accuracy and efficiency.

Each pico-droplet offers a regulated, delimited, and modifiable environment that preserves cell viability (Figure 1). Pico-droplets entrap secreted proteins, making them readily accessible for analysis and enabling rapid screening of single cells.

Multiple processes and tests throughout the cell line production pathway are downsized and integrated into Cyto-Mine®, enabling the completion of activities in a single day that would have otherwise taken weeks.

Utilizing this method, around 200,000 individual cells can be examined in a couple of hours, compared to approximately 10,000 cells using manual analytic approaches.

Screening is performed early on so that only cells expressing the desired protein and the best-performing cells within the pool are advanced in the development process, therefore enhancing the quality and quantity of molecular products.

Workflows have been drastically reduced from around 25 weeks to about ten weeks (Figure 2). Moreover, utilizing Cyto-Mine®, single cells can be viewed and correct monoclonality data can be supplied to assist regulatory applications.

Cyto-Mine® is built with user-friendly, integrated software that needs minimum specialized training to comprehend and use efficiently.

Cyto-Mine® has increased the overall effectiveness and productivity of the cell line and method development team at FUJIFILM DiosynthBiotechnologies. Scientists spend less time doing tedious manual methods and can accomplish more work within a given time frame.

This enables them to devote their specialized knowledge and talents to other crucial parts of their role. Scientists at FUJIFILM Diosynth Biotechnologies are already investigating further uses for this technological platform, inspired by the potential of Cyto-Mine® to improve or refine other facets of their study.

Cell line development with the Cyto-Mine®

Figure 1. Integration of productivity assay screening, sorting, isolation and verification using a fully automated picodroplet microfluidic process. Image Credit: Sphere Fluidics

Cell line development with the Cyto-Mine®

Figure 2. Example timeline highlighting the streamlining of workflows using mammalian cell line engineering technologies in combination with single-cell picodroplet innovations. Image Credit: Sphere Fluidics

Cell line development with the Cyto-Mine®

Figure 3. Accelerated cell line development workflow using Cyto-Mine®. Image Credit: Sphere Fluidics

The benefits of picodroplet technology

  • Streamlined and simplified processes
  • Miniaturization and integration of multiple processes/pathways
  • Accurately screening large cellular populations (200,000 individual cells)
  • Shortened timelines/workflows
  • Assured monoclonality
  • Increased efficiency
  • Automated processing and greater freedom from manual tasks

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About Sphere Fluidics

Our vision

Our philosophy is simple. We combine our knowledge and resources to help you find rare and valuable biological variants while helping you to save time, reduce costs and stay a step ahead of the competition.

Our novel single cell analysis systems offer the rapid screening and characterization of single cells. These systems are underpinned by our patented picodroplet technology, specifically designed to increase your chances of finding that rare ‘one-in-a-billion’ molecule or cell that could be an industry blockbuster.

We understand that time is of the essence. That’s why our technologies boost throughput and assay sensitivity across a range of applications. Most importantly, our flexible systems evolve alongside your changing research needs, providing an adaptable platform that helps you to meet your goals.

Our history

Founded in 2010, Sphere Fluidics is an established Life Sciences company, originally spun out from the University of Cambridge. We initially developed 25 patented products – biochips and specialist chemicals – which currently assist hundreds of customers globally with their research.

We initially focused on producing novel biochip systems and providing R&D services. We have since extended our expertise and are developing a technology platform that enables discovery in a range of growing markets through single cell analysis. Our systems make the development of new biopharmaceuticals faster and more cost-effective, improve monoclonal antibody screening, cell line development, and overall research efficiency in a number of other applications including synthetic biology, single cell diagnostics, prognostics and single cell genome editing.

The Cyto-Mine® Single Cell Analysis System is our flagship product – the first integrated, benchtop system to automatically analyze, sort and dispense millions of individual cells in just a single day.

Our partnerships

We value and are always open to discussing new collaborative, successful and innovative academic and industry partnerships to further develop and improve our single cell technologies.

Our Technology Access Programmes and Collaborative Services exist to enable academic researchers and companies alike to tap into our application-specific expertise through direct partnerships.

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Last updated: Apr 12, 2024 at 9:58 AM


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