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A Uniquely Scalable Approach to Sequence Tens of Millions of Single Cells Without Compromising Performance

一种独特的可扩展方法，可在不影响性能的情况下对数千万个单细胞进行测序

基本信息

批准号：
10700398
负责人：
Philipp Stefan Spuhler
金额：
$ 27.56万
依托单位：
SANSIMEON, INC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10700398
关键词：
Acceleration Adoption Aftercare Antibodies Authorization documentation Bar Codes Barbering CAR T cell therapy CRISPR screen CRISPR/Cas technology Cell Size Cell Survival Cell Therapy Cells Cellular immunotherapy Clonal Expansion Clustered Regularly Interspaced Short Palindromic Repeats DNA sequencing Development Disease Disease remission Doctor of Philosophy Drops Encapsulated Engineering Evaluation Funding Generations Genes Genome Genome engineering Goals Government Grant Immune Immune response Immunologic Receptors Immunotherapy Individual Jurkat Cells K562 Cells Label Marketing Methods Microfluidics Noise Oils Pathogenesis Pathway interactions Patient Monitoring Patients Performance Persons Pharmaceutical Preparations Phenotype Population Price Property Research Personnel Role Sampling Signal Transduction Small Business Innovation Research Grant Speed System T-Cell Receptor Testing Translational Research Variant Water Work adaptive immune response authority cellular engineering combinatorial commercial launch cost droplet sequencing experimental study expiration genome-wide improved indexing innovation meter nanoDroplet next generation operation prototype response scale up sequencing platform single cell analysis single cell sequencing success technology development tool development treatment response

项目摘要

Immunotherapies (including CAR-T cell therapies) are wonder drugs when they work, but the response rates of today’s immunotherapies are only 15-20% and therapy costs remain prohibitively high for mass adoption. Recent advances in single cell sequencing make it a critical tool for the development of next generation cell therapies through high impact applications such as TCR immune profiling and pooled CRISPR screening. Unlocking the value of these applications requires interrogation of >10 million cells per experiment. Expiration of Illumina’s core IP in 2023 re-ignited competition in US & EU markets and re-accelerated the drop in DNA sequencing costs to make sequencing of ~10 million cells affordable in 1-2 years, but existing methods for single cell barcoding do not support throughput beyond 1 million cells per experiment. Proposed alternatives are scalable, but trade-offs in performance and ease-of-use make them unsuitable for translational research. Sansimeon’s approach uniquely enables scaled single cell sequencing with throughput to 100M cells, while retaining high ease-of-use and necessary cell capture efficiency for high-throughput applications in translational research. The platform overcomes throughput limitations common to other drop-seq approaches by leveraging rapid deterministic pairing of single cells with single beads in a microchannel prior to emulsification, without the need for multi-step labeling workflows such as cell-hashing or combinatorial indexing.

免疫疗法（包括CAR-T细胞疗法）在起作用时是神奇的药物，但当今免疫疗法的反应率仅为15-20%，高得让人望而却步单细胞测序的最新进展使其成为关键的通过高影响力应用开发下一代细胞疗法的工具，作为TCR免疫分析和合并的CRISPR筛选。释放这些价值应用要求每次实验询问> 1000万个细胞。Illumina的核心 2023年的知识产权重新点燃了美国和欧盟市场的竞争，并重新加速了DNA的下降在1-2年内使~ 1000万个细胞的测序负担得起的测序成本，但现有的用于单细胞条形码化的方法不支持每个实验超过1百万个细胞的通量。建议的替代方案是可扩展的，但性能和易用性的权衡使它们不适合翻译研究。Sansimeon的方法独特地使规模化的单细胞测序通量可达1亿个细胞，同时保留高易用性和必要的细胞转化研究中高通量应用的捕获效率。平台克服了其他drop-seq方法常见的通量限制，乳化前微通道中单细胞与单珠的确定性配对，而不需要多步骤标记工作流程，例如单元散列或组合索引。