Abstract

Circulating tumor cells (CTCs) have become an established biomarker for prognosis in patients with various carcinomas. However, current ex vivo CTC isolation technologies rely on small blood volumes from a single venipuncture limiting the number of captured CTCs. This produces statistical variability and inaccurate reflection of tumor cell heterogeneity. Here, we describe an in vivo indwelling intravascular aphaeretic CTC isolation system to continuously collect CTCs directly from a peripheral vein. The system returns the remaining blood products after CTC enrichment, permitting interrogation of larger blood volumes than classic phlebotomy specimens over a prolonged period of time. The system is validated in canine models showing capability to screen 1–2% of the entire blood over 2 h. Our result shows substantial increase in CTC capture, compared with serial blood draws. This technology could potentially be used to analyze large number of CTCs to facilitate translation of analytical information into future clinical decisions.

Ex vivo methods of circulating tumor cell (CTC) isolation use small blood volumes, limiting sensitivity and introducing analytical inaccuracies. The authors describe a proof-of-concept study of an in vivo aphaeresis system that continuously collects CTCs from a peripheral vein over several hours.

Details

Title
A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells
Author
Kim, Tae Hyun 1   VIAFID ORCID Logo  ; Wang, Yang 2 ; Ryan, Oliver C 3 ; Thamm, Douglas H 4 ; Cooling, Laura 5 ; Paoletti Costanza 6 ; Smith, Kaylee J 7 ; Nagrath Sunitha 2   VIAFID ORCID Logo  ; Hayes, Daniel F 6   VIAFID ORCID Logo 

1  University of Michigan, Department of Chemical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Electrical Engineering and Computer Science, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Biointerfaces Institute, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Biomedical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
2  University of Michigan, Department of Chemical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Biointerfaces Institute, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
3  University of Michigan, Biomedical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
4  Colorado State University, Flint Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, USA (GRID:grid.47894.36) (ISNI:0000 0004 1936 8083) 
5  University of Michigan, Department of Pathology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
6  University of Michigan Rogel Cancer Center, Department of Internal Medicine, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
7  University of Michigan, Department of Chemical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-09439-9
ProQuest document ID
2201701112
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.