ValveCCI-seq: An Advanced Microfluidic Approach for Deciphering Cell-Cell Interactions

Area of Science:

• Biotechnology
• Immunology
• Genomics

Background:

• Immunotherapy efficacy relies on precise immune cell interaction modulation.
• Current cell-cell interaction analysis methods have limitations in throughput, efficiency, and preserving cell identity.

Purpose of the Study:

• To develop a high-resolution platform for profiling cell-cell interactions while preserving cell identities.
• To overcome the limitations of existing transcriptome-based methods for analyzing cell-cell interactions.

Main Methods:

• Developed ValveCCI-seq, a microfluidic platform integrating deterministic cell-pairing and in situ sequencing.
• Achieved high throughput (32,000 cell pairs/hour) and efficiency (>86%) with broad cell compatibility.
• Enabled direct transcriptome profiling of co-encapsulated cell pairs within droplets, preserving cell-pair identities.

Main Results:

• ValveCCI-seq revealed gene expression signatures linked to T-cell activation using Jurkat and T2 cells.
• Demonstrated precise identification of tumor antigens and cognate T-cell receptor (TCR) sequences.
• Preserved interacting cell identities and enabled high-throughput analysis.

Conclusions:

• ValveCCI-seq offers a robust framework for advancing cell therapy development.
• Facilitates systematic studies of cellular interactions in clinical samples.
• Supports parallel TCR screening across multiple antigens.