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. Single-cell sequencing (SC-seq) is becoming the preferred tool for immune profiling to map a patient’s adaptive immune response, and to readout phenotypic changes that result from CRISPR based gene edits at the single cell level. However, the full potential of SC-seq based CRISPR screens and immune repertoire profiling for the development of next generation therapeutics requires a 10-fold to 100-fold increase in cell throughput relative to current platforms. Upcoming expiration of Illumina’s core IP re-ignited competition in US & EU markets. The resulting re-acceleration in the drop of DNA sequencing costs (6-fold price reduction in 2023 vs. Illumina’s 2022 pricing) makes SC-seq of 10 million cells affordable today (20-30 million cells in ~3 years and 100 million cells in 6 years), but existing methods for SC-seq 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 scales SC-seq with throughput >100M cells, while retaining the ease-of-use and necessary cell capture efficiency for high-throughput applications in translational research. Our platform incorporates a technology for in-line sample debulking, which was previously commercialized for applications in cell therapy manufacturing and rare cell isolation. Sansimeon’s ability to sequence >100 million single cells directly from crude & complex samples (such as whole blood or bone marrow aspirates), with a single-step automated workflow, makes the platform ideally suited for high-throughput applications in translational research.