Spatially resolved single-cell DNA sequencing: a general spatial genomics platform with application to HIV reservoir mapping

The National Institute of Allergy and Infectious Diseases awarded Vivid Bioinnovations, PBC $299,991 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a spatially resolved single-cell DNA sequencing platform for spatial genomics with application to HIV reservoir mapping.

The recipient will develop the first commercially viable spatial genomics platform integrating hydrogel-based spatial barcoding, droplet microfluidics, and Bayesian reconstruction algorithms to simultaneously capture DNA, RNA, and protein from individual cells while preserving spatial context. The system is designed to analyze tissue sections containing hundreds of thousands to up to one million cells per run at a cost comparable to existing spatial genomic technologies. The work addresses a critical gap in current spatial genomics platforms, which lack the ability to sequence genomic DNA in situ—a capability with broad applications in cancer, infectious diseases, and neurodegeneration research. In Phase 1, the recipient will adapt and integrate proven academic methods into a robust commercial prototype and validate performance using HIV-positive spike-ins and primary specimens. Phase 2 will optimize hardware and software integration for enhanced reproducibility and scalability.

Work is performed in San Francisco, California. The period of performance runs from September 1, 2026, through August 31, 2027.

Abstract

Spatial genomics has emerged as a transformative approach over the past five years, with numerous platforms now enabling high-resolution mapping of cellular transcripts and proteins. However, these instruments all share a critical limitation: the inability to sequence genomic DNA in situ. Genomic DNA is inherently challenging to assay because IT is embedded in chromatin and bound by nuclear proteins, rendering IT less accessible to probes. Moreover, being present as a single copy per cell, its detection requires extremely sensitive methods. This GAP is significant given that genomic DNA is fundamental to understanding basic biology and has broad applications in areas such as cancer, infectious diseases, and neurodegeneration, where somatic mutations play a pivotal role. This proposal will develop the first commercially viable spatial genomics platform that integrates hydrogel-based spatial barcoding, advanced droplet microfluidics, and innovative bayesian reconstruction algorithms to simultaneously capture DNA, RNA, and protein from individual cells while preserving their native spatial context. The system is designed to analyze tissue sections containing from hundreds of thousands to up to one million cells per run at a cost comparable to existing spatial genomic technologies, making IT feasible for large-scale tissue mapping. Building on extensive academic research, published protocols, and collaborations with world-class institutions, our approach will be demonstrated through a focused application in HIV reservoir mapping. In phase 1, we will adapt and integrate these proven methods into a robust commercial prototype and rigorously validate its performance using HIV-positive spike-INS and primary specimens. In phase 2, we will optimize hardware and software integration for enhanced reproducibility and scalability, expand validation to additional specimen types, and develop a comprehensive target product profile through beta testing with academic and industry partners.