Spatially Tunable Multiomic Sequencing Using Light-Driven Combinatorial Barcoding of Molecules in Tissues

Why It Matters

BALI removes key barriers—limited multiplexing, high expense, and rigid spatial designs—making large‑scale, multi‑omic tissue mapping feasible for both academic labs and biotech pipelines.

Key Takeaways

• BALI uses light-driven combinatorial barcoding for spatial multiomics.
• Users can define number, size, shape, resolution of regions.
• Demonstrated transcriptome and chromatin accessibility profiling in mouse brain.
• Integrated instrument automates barcode writing for high‑throughput runs.
• BALI compatible with standard histology pipelines, enabling scalable studies.

Pulse Analysis

Spatial omics has reshaped how scientists interrogate tissue architecture, but most platforms trade off resolution, depth, or cost. Traditional methods either focus on a single molecular layer—such as RNA or proteins—or require expensive, custom microarrays that limit sample throughput. Researchers have long sought a flexible, affordable solution that can capture multiple biomolecule classes while preserving spatial context, especially for large‑scale studies in disease models and drug development.

Enter BALI, a light‑activated combinatorial indexing system that writes DNA barcodes directly onto target molecules in situ. By projecting patterned illumination, the method sequentially ligates index oligos, building a unique spatial code for each defined region. Users can program the number, size, shape and resolution of these regions, from whole‑tissue zones down to subcellular compartments, potentially generating millions of distinct barcodes. In mouse brain sections, BALI simultaneously captured transcriptomic and chromatin‑accessibility signals, matching public reference atlases and demonstrating the platform’s accuracy across modalities.

The broader impact of BALI lies in its scalability and compatibility with existing histology workflows. The automated instrument reduces hands‑on time, lowering per‑sample costs and opening spatial multi‑omics to larger cohorts and clinical specimens. As biotech firms and academic consortia aim to build comprehensive tissue atlases, BALI’s tunable design could accelerate biomarker discovery, improve patient stratification, and enable new therapeutic insights. Continued integration with downstream analysis pipelines and expansion to protein or epigenetic marks will further cement its role as a cornerstone technology in next‑generation spatial biology.