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

Author

Listed:
  • 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
    Georgia Institute of Technology)

  • Bassel Nazha

    (Emory University
    Emory University School of Medicine)

  • Omer Kucuk

    (Emory University
    Emory University School of Medicine)

  • Martin G. Sanda

    (Emory University School of Medicine)

  • Benedict B. Benigno

    (Georgia Institute of Technology
    Ovarian Cancer Institute)

  • Carlos S. Moreno

    (Emory University
    Emory University School of Medicine)

  • Mehmet A. Bilen

    (Emory University
    Emory University School of Medicine)

  • John F. McDonald

    (Georgia Institute of Technology
    Georgia Institute of Technology
    Georgia Institute of Technology
    Ovarian Cancer Institute)

  • A. Fatih Sarioglu

    (Georgia Institute of Technology
    Georgia Institute of Technology
    Emory University
    Georgia Institute of Technology)

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.

Suggested Citation

  • 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 & Ome, 2022. "High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31009-9
    DOI: 10.1038/s41467-022-31009-9
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    References listed on IDEAS

    as
    1. Sunitha Nagrath & Lecia V. Sequist & Shyamala Maheswaran & Daphne W. Bell & Daniel Irimia & Lindsey Ulkus & Matthew R. Smith & Eunice L. Kwak & Subba Digumarthy & Alona Muzikansky & Paula Ryan & Ulyss, 2007. "Isolation of rare circulating tumour cells in cancer patients by microchip technology," Nature, Nature, vol. 450(7173), pages 1235-1239, December.
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    Cited by:

    1. Xiaoxu Guo & Fanghe Lin & Chuanyou Yi & Juan Song & Di Sun & Li Lin & Zhixing Zhong & Zhaorun Wu & Xiaoyu Wang & Yingkun Zhang & Jin Li & Huimin Zhang & Feng Liu & Chaoyong Yang & Jia Song, 2022. "Deep transfer learning enables lesion tracing of circulating tumor cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Yiming Ma & Jun Zhang & Yunqing Tian & Yihao Fu & Shu Tian & Qingsi Li & Jing Yang & Lei Zhang, 2023. "Zwitterionic microgel preservation platform for circulating tumor cells in whole blood specimen," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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