Abstract Background: Circulating tumor cells (CTCs) have great potential as biomarkers for the diagnosis and prognosis of many cancers. The CapioCyteTM chip isolates live CTCs through a unique combination of biomimetic cell rolling and nanoparticle-mediated multivalent immunorecognition. Recently-published work reported the highly sensitive and specific CTC capture from 24 patients in a pilot study [Myung et al., Clinical Cancer Research 2018, 24(11):2439-2547]. Here, we report results from additional cohorts of patients and demonstrate downstream analysis of captured CTCs. Methods: Peripheral blood samples were collected from patients undergoing radiotherapy (RT) (n=12; oligometastic n = 5, head and neck cancer n = 1, non small cell lung cancer n = 2, prostate cancer n = 3, cervical cancer n = 1) or immunotherapy (n=4). Samples were processed the next day by CapioCyteTM chips designed for the immunoisolation cells expressing epithelial cell adhesion molecule (EpCAM), human epidermal growth factor-2 (HER-2), and epidermal growth factor receptor (EGFR). Captured CTCs were identified by immunocytochemistry as containing round nuclei, positive expression of cytokeratin, and negative expression of CD45. Select samples were recovered from the capture surface and submitted for single cell gene expression assays (RNASeq) using 10X Genomics Chromium barcoding and Illumina next-generation sequencing. Results: Immunocytochemical staining identified CTCs in all pre-treatment blood samples from patients undergoing RT (mean 95 CTC/ml whole blood, SE 54, range 4-680) and immunotherapy (mean 70 CTC/ml whole blood, SE 16, range 39-104). CTC counts decreased with time points collected during and post-treatment, consistent with other measures of treatment progress. Single cell RNASeq confirmed the presence of tumor-derived cells in select samples and, importantly, demonstrated the ability to conduct downstream analysis of CTCs isolated on the CapioCyteTM chip. Conclusions: The CapioCyteTM chip effectively captures CTCs for quantification and downstream analysis requiring viable cells such as RNASeq. The liquid biopsy technology has great potential to contribute to diagnosis and personalized treatment of cancer. Citation Format: Michael J. Poellmann, Jiyoon Bu, Dominic Moon, Kyle Wagner, Andrew Z. Wang, Seungpyo Hong. Quantification and downstream analysis of circulating tumor cells isolated using CapioCyteTM liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 410.