Personalized cancer therapies currently rely on profiling tissue biopsies from primary or metastatic lesions to identify therapeutic targets. However, these conventional approaches are limited by their invasive nature, precluding repeated sampling, and often failing to capture complex intratumoral heterogeneity. Circulating tumor cells (CTCs), the biological drivers of metastasis, offer a minimally invasive liquid-biopsy alternative to overcome the static limitations of tissue biopsies. Moreover, CTC profiling offers an accurate strategy for assessing tumor heterogeneity, monitoring longitudinal disease evolution, and guiding targeted interventions. Despite their clinical potential, robust methods to collect and analyze the molecular profile of CTCs with sufficient resolution for clinical utility are lacking, largely because of the small sampling volumes used in standard liquid biopsy approaches (~ 7.5 mL).

The TzuPlus® platform provides an integrated, end-to-end workflow for CTC isolation and multi-omic molecular characterization. First, TzuFETCH® technology enriches and captures CTCs from large blood volumes (~ 2–5 L) derived from leukapheresis products. Next, the BD FACSDiscover™ S8 cell sorter is used to profile surface markers and isolate CTCs. Single cells are then processed using proprietary in-house protocols to generate unique, full-length long-read transcriptomic and whole-genome sequencing libraries, followed by sequencing. Finally, dedicated bioinformatic pipelines analyze and integrate these multi-omic profiles to report actionable genomic alterations and druggable targets expressed in individual CTCs.

TzuFETCH® technology has been validated on dozens of clinical samples and proven effective at increasing CTC capture sensitivity through leukapheresis, which can achieve up to a 200-fold greater enrichment over standard methods and enables CTC isolation even in patients with low CTC numbers. Validation using healthy donor blood spiked with prostate (LNCaP) and gastric (KATO III) cancer cell lines, followed by single-cell genome and transcriptome profiling, produced high-quality genomic data reproducible across replicates and preserved transcriptomic signatures across the entire TZUPlus® workflow. Applying the same pipeline to four CTCs from a prostate cancer patient showed that robust, high-resolution molecular profiles can be routinely generated from individual CTCs.

TzuPlus® enables routine, minimally invasive monitoring of tumor heterogeneity through marker analysis of CTCs combined with deep single-cell genomic and/or transcriptomic profiling from large blood volumes. Integrating CTC-derived multi-omics profiles into a patient-specific circulating cancer catalog supports identification of clone-specific therapeutic targets and patient stratification for personalized decision-making in precision oncology.