Combinatorial indexing, often called split-pool barcoding, is a method for tagging DNA or RNA from many individual cells or nuclei with unique combinations of short index sequences across multiple rounds of pooling and splitting, so that reads can later be traced back to their cell of origin without isolating each cell physically. It allows a single sequencing run to process far more cells than droplet-based methods at a lower cost per cell. The patent literature in this space, 359 records as of mid-2026, covers the core barcoding method along with practical problems like index hopping, nuclei integrity, and protocol complexity.

The assignee ranking for this dataset covers 69 companies and research institutions, but it is heavily front-loaded: the leading assignee holds 236 of the 359 records in scope, while the fifth-ranked entity holds 24 and the tenth holds 7. Several university and research-institute names also appear near the top of the ranking, often as co-assignees alongside the leading commercial filer. This pattern indicates the foundational method was developed and patented through a small number of academic-commercial partnerships rather than broadly across the industry.

Filing activity peaked at 96 records in 2019 and had fallen to 14 by 2024, a -79% decline over that three-year span, which is the most recent period that can be read reliably given an approximately 18-month gap between filing and publication. Figures for 2025 and 2026 in the raw data appear near zero, but that reflects publications still working through the pipeline rather than an actual stop in R&D. The safer read is that the core method is now well-established and heavily claimed, which naturally slows the pace of new foundational filings even as application-specific work continues.

US20260201460A1, filed by Chapter Diagnostics, Inc. and published 2026-07-16, describes quadruple combinatorial indexing methods to reduce index hopping when many samples share a sequencing run, including the addition of unique index sequences to each DNA fragment during library preparation. It is one of the most recent filings in this dataset and targets a specific failure mode — misassignment of reads during demultiplexing — rather than the base split-pool method itself. Anyone building a competing index-hopping mitigation approach should review its claim scope closely, particularly around the specific indexing scheme and sample-multiplexing thresholds it describes.

The IPC composition shows claims concentrated in C12Q and C12N, covering 76.9% and 47.9% of the 359 records respectively, while combinatorial chemistry library claims (C40B) sit at just 12.0% and bioinformatics-specific claims (G16B) at only 1.1%. That gap suggests narrower opportunities in areas like demultiplexing algorithms, instrument-free protocol variants, and nuclei-integrity-specific chemistries, where fewer records compete for claim space even though the underlying application is well established. A first claim in these areas would likely need to tie a specific chemistry or algorithmic step to a measurable outcome, such as reduced collision rate or improved cost per cell, rather than claiming the split-pool concept broadly.