Multimodal single-cell and whole-genome sequencing from small amounts of frozen tissue

This technology is a method for generating single-cell profiles from small tissue samples of clinical grade or research specimens.

Unmet Need: Improved single-cell sequencing efficiency and compatibility with frozen tissue

Single-cell sequencing has revolutionized biological and translational research, including in fields like oncology, by enabling the analysis of individual cells. This technology provides a higher resolution of cellular differences and a deeper understanding of cells in their microenvironments. However, its application in large-scale, clinical-grade research has been hindered by challenges such as the need for sample optimization, large input volumes, complex workflows, and variable data quality, especially when working with precious fresh tissue. To overcome these limitations, simpler methods of single-cell sequencing that require less input material are needed. Additionally, the ability to use frozen tissue would facilitate both retrospective and prospective studies, while also reducing variability in data quality that can compromise tissue samples.

The Technology: Multimodal single-cell sequencing method from small input volumes and frozen samples

This technology is a method for generating single-cell profiles from smaller input volumes, capable of producing multiple readouts, including transcriptomics, T-cell repertoires, spatial sequencing, CNV-sequencing, DNA sequencing, and more. This approach reduces the amount of optimal-cutting temperature (OCT) compound required for embedded tissue and minimizes sample weight requirements while improving efficiency. The technology also maintains tissue integrity, enabling multi-modal studies of samples and facilitating both retrospective and prospective studies using fresh and snap-frozen samples. This technology will extend the applications of single-cell sequencing across various research and clinical settings.

This technology has been validated through integrated clinical and single-cell profiling analyses in patients with pancreatic ductal adenocarcinoma and non-small cell lung cancer, as well as by the Human Immune Monitoring Core (HIMC) across diverse sample types.

Applications:

• Single-cell profiling of clinical-grade specimens for diagnostic, prognostic, and treatment purposes
• Research tool for analysis of frozen specimens in oncology studies such as assessing cellular and disease states (e.g., tumor microenvironments)
• Retroactive and prospective single-cell studies across research disciplines
• Multi-modal studies of the same sample fractions
• Assessment of previously preserved frozen samples

Advantages:

• High efficiency
• Allows preservation of tissue and frozen specimens and tissue integrity
• Cost-effective
• Enables multimodal analysis: single-cell transcriptomics, T-cell repertoires, spatial sequencing, DNA, SNP, and CNV sequencing
• Simplified workflow
• Improved data quality and reduced variability due to the ability to work with frozen tissue
• Reduced interference with RNA processing

Lead Inventor:

Benjamin Izar, M.D., Ph.D.

Patent Information:

Patent Pending (WO/2023/154732)

Related Publications:

• Luthria K, Shah P, Caldwell B, Melms JC, Abuzaid S, Jakubikova V, Brodtman DZ, Bose S, Amin AD, Ho P, Biermann J, Tagore S, Ingham M, Schwartz GK, Izar B. “Single-cell profiling of sarcomas from archival tissue reveals programs associated with resistance to immune checkpoint blockade.” Clin Cancer Res. 2024 Oct 1; 30(19):4530-4541.

Tech Ventures Reference:

• IR CU21047

• Licensing Contact: Joan Martinez