Negative enrichment of circulating tumor cells from unmanipulated whole blood with a 3D printed device

• Published in: Scientific reports Vol. 11; no. 1; p. 20583
• Main Authors: Chu, Chia-Heng, Liu, Ruxiu, Ozkaya-Ahmadov, Tevhide, Swain, Brandi E., Boya, Mert, El-Rayes, Bassel, Akce, Mehmet, Bilen, Mehmet Asim, Kucuk, Omer, Sarioglu, A. Fatih
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-10-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/277; 631/67; 631/67/2322; Adult; Aged; Antigens; Biopsy; Blood; Cell Count; Cell differentiation; Cell Line, Tumor; Cell Separation - methods; Cell size; Female; Humanities and Social Sciences; Humans; Lab-On-A-Chip Devices; Leukocytes; Leukocytes - cytology; Male; Microfluidic Analytical Techniques - instrumentation; Microfluidics; Middle Aged; multidisciplinary; Neoplastic Cells, Circulating - metabolism; Neoplastic Cells, Circulating - pathology; Pancreatic cancer; Peripheral blood; Pilot Projects; Printing, Three-Dimensional; Prostate; Science; Science (multidisciplinary); Surface antigens; Tumor cells; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-99951-0

Reliable and routine isolation of circulating tumor cells (CTCs) from peripheral blood would allow effective monitoring of the disease and guide the development of personalized treatments. Negative enrichment of CTCs by depleting normal blood cells ensures against a biased selection of a subpopulation and allows the assay to be applied on different tumor types. Here, we report an additively manufactured microfluidic device that can negatively enrich viable CTCs from clinically-relevant volumes of unmanipulated whole blood samples. Our device depletes nucleated blood cells based on their surface antigens and the smaller anucleated cells based on their size. Enriched CTCs are made available off the device in suspension making our technique compatible with standard immunocytochemical, molecular and functional assays. Our device could achieve a ~ 2.34-log depletion by capturing > 99.5% of white blood cells from 10 mL of whole blood while recovering > 90% of spiked tumor cells. Furthermore, we demonstrated the capability of the device to isolate CTCs from blood samples collected from patients (n = 15) with prostate and pancreatic cancers in a pilot study. A universal CTC assay that can differentiate tumor cells from normal blood cells with the specificity of clinically established membrane antigens yet require no label has the potential to enable routine blood-based tumor biopsies at the point-of-care.