Cyto-Mine® Next-Generation Single Cell Analysis

Existing processes used for developing stable cell lines for the production of biotherapeutics or identifying new antibody targets are not only time consuming but also inefficient. Regardless of whether individuals are screening CHO cells, hybridoma populations, whole B cell repertoires, or other cell types, methods like clone picking, cell sorting¸ or limiting dilutions have inherent disadvantages.

For example, some approaches are likely to be harsh on the individual cells and can have an impact on the viability and outgrowth of cells, while some methods do not enable cell secretion assays. Moreover, current methods are costly, suboptimal, and involve numerous individual steps, and hence may lead to problems like contamination and human error.

Cyto-Mine® is the next-generation single cell analysis system that enables users to simplify, automate, and speed up their antibody discovery as well as cell line development workflows.

The first integrated device to automatically perform selective screening, cell isolation and clone verification in a single compact system.

Targeted Discovery — Users can quickly detect and isolate their rare cells of interest

Monoclonality Assurance — Elegant proof of monoclonality for the development of cell lines

Considerably Reduce Costs and Timelines — Hundreds of thousands of cells individually or tens of millions of cells in pools are screened in one day

Flexibility — Antibody secretion can be quantitatively measured through easy and flexible fluorescent assays

Sterility — The whole process is sterile, automated, and Animal Origin Free. The Benchtop cell analysis system is adaptable for use in Class II biosafety cabinets

Cyto-Mine® — The Technology

Cyto-Mine® is the first integrated device to automatically perform selective screening, clone verification and cell isolation in a single compact system.

This high-throughput instrument utilizes microfluidics and picodroplet technology to process around 40 million heterogeneous mammalian cells (in pools), and all this is done in less than a day. Biocompatible oil and surfactant pinch a stream of cells, assay reagents and culture media to encapsulate cells into a picodroplet. The picodroplets serve as mini bioreactors for individual compartmentalize cells, as secreted proteins from single cells accumulate in the picodroplets they bind to assay reagents, enabling the identification of valuable proteins (e.g. antibodies) to find rare cells of interest or cells with high productivity.

Thanks to the unique workflow, single cells can be selectively screened for detecting rare lead candidates. Although the platform was mainly developed for antibody discovery and cell line development, its flexibility makes it appropriate for a wide range of application areas.

There is a strong assurance of monoclonality when single cells are compartmentalized in separate picodroplets. This allows users to carry out new assays and thus establish antigen-specificity, titre, and protein secretion rates. In addition, capturing single cells in picodroplets facilitates smooth processing all through the workflow.

Since each run occurs on a disposable single-use Cyto-Cartridge®, users can be confident of sterility and this translates to reduced crossover risks. System automation reduces the requirements for human resources, and the simple “load-and-go” format is effortlessly used by everyone in the laboratory.

Cyto-Cartridge®, Cyto-Mine®, and Sphere Fluidics’ bioreagents and specialist chemicals are all GLP-compliant and Animal Origin Free.

Watch Cyto-Mine® in Action

Benefits

Flexible Assay Design for Antibody Screening

Cyto-Mine® technology is designed to facilitate fast, miniaturized assays of target proteins released from encapsulated cells. Furthermore, assay format can be customized to suit users’ requirements.

Whether it is antigen-specific assays for B cell mining, IgG secretion assays for productivity screens, customized assays to measure functionality, hybridoma fusion screens, reporter assays or post-translational modifications, Sphere Fluidics has a solution for everyone.

Evidence of Monoclonality

Undoubtedly, there is a growing requirement for proof of monoclonality in single cell analysis. In this context, Cyto-Mine® provides evidence of a single cell status in several ways. At first, cells are encapsulated into picodroplets at extreme dilution so that the chances of two or more cells per picodroplet are drastically low (approximately 0.1%). Exclusively, ultra-high speed, multi-frame optical imaging provides visual proof of monoclonality before dispensing.

Single Cell Assays

The advanced Cyto-Mine® picodroplet technology offers a new, robust method for screening huge amounts of cells for secreted proteins. Flexible assay set up combined with the picodroplet method means that the unique platform can be configured to suit individuals’ requirements. Whether users are working in synthetic biology, antibody discovery, cell line development, cell therapy development, genome editing or any other fields, the platform is highly flexible.

Applications

Primary B Cell Analysis

New advances in antibody discovery, via single cell gene sequencing and recombinant immunoglobulin expression, have allowed direct screening of B lymphocytes or native B cells. This provides the possibility to deep-mine the mammalian immune system repertoire more thoroughly. Being an exclusive platform, Cyto-Mine® enables users to quickly screen a huge number of native B cells to detect rare cells of interest.

Hybridoma Screening

In antibody drug discovery, hybridoma generation and screening is considered a robust tool. Present methods employed in the field are limited by the number of hybridomas that can be screened per day, slowing down pipelines. However, these challenges are resolved by Cyto-Mine®, which enables users to speed up their hybridoma screening.

Cell Line Development

The Cyto-Mine® single cell analysis enables users to quickly screen an unlimited number of mammalian clones and simultaneously dispense user-defined candidate clones, for example, highest producers. In addition, clone screening becomes gentler and faster, considerably reducing costs related to workflows. Proof of monoclonality is also offered with a range of images before dispensing single cells to individual wells of a 384- or 96-well plate.