High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells

• Type of Material: Article
• Authors: Mert Boya, Georgia Institute of Technology; Tevhide Ozkaya-Ahmadov, Georgia Institute of Technology; Brandi E. Swain, Georgia Institute of Technology; Chia-Heng Chu, Georgia Institute of Technology; Norh Asmare, Georgia Institute of Technology; Ozgun Civelekoglu, Georgia Institute of Technology; Ruxiu Liu, Georgia Institute of Technology; Dohwan Lee, Georgia Institute of Technology; Sherry Tobia, University Gynecologic Oncology; Shweta Biliya, Georgia Institute of Technology; L. DeEtte McDonald, Georgia Institute of Technology; Bassel Nazha, Emory University; Omer Kucuk, Emory University; Martin Sanda, Emory University; Benedict B. Benigno, Georgia Institute of Technology; Carlos Moreno, Emory University; Mehmet Bilen, Emory University; John F. McDonald, Georgia Institute of Technology; A. Faith Sarioglu, Georgia Institute of Technology
• Language: English
• Date: 2022-06-13
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-022-31009-9
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 13
• Issue: 1
• Start Page: 3385
• End Page: 3385
• Grant/Funding Information: This work was supported by the start-up funds provided to A.F.S. by Georgia Institute of Technology. The research was also supported in part by the Office of the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program under Award No. W81XWH-20-1-0649 (A.F.S.), Georgia Tech Petit Institute Seed Grant (A.F.S. and J.F.M.), the Dunwoody Golf Club Prostate Cancer Research Award, and Winship Invest$ Pilot Grant from the Winship Cancer Institute of Emory University (A.F.S. and M.A.B.).
• Keywords: PROGNOSTIC-SIGNIFICANCE; Science & Technology; CANCER-PATIENTS; MALIGNANT ASCITES; CAPTURE; Science & Technology - Other Topics; Multidisciplinary Sciences; METASTASIS; COLORECTAL-CANCER; BLOOD
• Research Categories: Health Sciences, Oncology; Biology, Cell

Abstract

Extremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The >100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of >25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2 to 100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.