MULTI-MODAL, SAME-CELL ASSAY FOR SEQUENCING AND PROTEIN DETECTION

Researchers at UC Berkeley have developed a platform that enables unified proteomic and nucleic acid-based omics analysis from the same cell. 

Current multiplex assays, such as those relying on commercial systems like 10XGenomics, are limited in their ability to detect surface or intra-nuclear proteins and they require prior knowledge of target proteins to design specific antibody-oligo conjugates. They also typically require nuclei fixation which may limit subsequent analyses. This presents a particular challenge when an unexpected finding arises from next-generation sequencing, as there is no way to retrospectively assess corresponding protein expression. 

Stage of Research

The inventors have developed Blot-seq, a platform that isolates single cells in polyacrylamide gel microwells and separates cellular compartments for nucleic acid sequencing and protein detection, while also spatially preserving proteins for future analysis. 

Applications

• Organelle-biology and subcellular omics. 
• Single-nucleus isolation using microwell-isolated mammalian cells. 

Advantages

• Blot-seq enables a “target-discover-target” workflow where nucleic acid assay results guide subsequent protein assays, eliminating the need for prior knowledge about the proteins of interest. 
• Blot-seq enables unified proteomic and nucleic acid-based omics analysis from the same cell. 
• Blot-seq preserves the proteome for repeated post-sequencing interrogation and facilitates hypothesis-driven investigation of single-cell heterogeneity. 
• Blot-seq overcomes the limitations of existing multimodal assays, which require nucleic acid fixation and do not address protein isoforms. 

Stage of Development

Research – in vitro

Keywords

Sequencing, single cell, multiplex, protein, nucleic acid

Technology Reference: 

CZ Biohub SF ref. no. CZB-322B

Berkeley ref. no. BK2025-052