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

Mert Boya, Tevhide Ozkaya-Ahmadov, Brandi E. Swain, Chia-Heng Chu, Norh Asmare, Ozgun Civelekoglu, Ruxiu Liu, Dohwan Lee, Sherry Tobia, Shweta Biliya, L. DeEtte McDonald, Bassel Nazha, Omer Kucuk, Martin G. Sanda, Benedict B. Benigno, Carlos S. Moreno, Mehmet A. Bilen, John F. McDonald and A. Fatih Sarioglu ()
Additional contact information
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 G. Sanda: Emory University School of Medicine
Benedict B. Benigno: Georgia Institute of Technology
Carlos S. Moreno: Emory University
Mehmet A. Bilen: Emory University
John F. McDonald: Georgia Institute of Technology
A. Fatih Sarioglu: Georgia Institute of Technology

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31009-9

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