Single-Cell Droplet Microfluidic Screening for Antibodies Specifically Binding to Target Cells

Area of Science:

• Biotechnology
• Immunology
• Microfluidics

Background:

• Monoclonal antibodies are crucial in drug discovery, with cell-surface receptors being key targets.
• Existing antibody screening methods face limitations in detecting binding to cell-surface receptors or whole cells.

Purpose of the Study:

• To develop a high-throughput droplet microfluidics assay for screening antibody binding to target cells.
• To enable quantitative analysis of antibody-mediated cell recognition with minimal sample input.

Main Methods:

• Utilized droplet microfluidics with dual-color normalized fluorescence readout for antibody detection.
• Co-encapsulated hybridoma cells and target cells within droplets for single-cell screening.
• Employed a high-throughput sorting system to enrich specific antibody-secreting clones.

Main Results:

• Achieved quantitative data on target cell recognition using as little as 33 fg of IgG.
• Enriched specific antibody binders 220-fold by sorting 80,000 hybridoma clones in one experiment.
• Demonstrated the potential for screening antibodies against cell-surface targets and whole cells.

Conclusions:

• The droplet microfluidics approach offers a powerful tool for therapeutic antibody discovery.
• This single-cell method is adaptable for screening antibodies from primary human plasma cells.
• The assay facilitates efficient enrichment of specific antibody binders for drug development.