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

Author:

Boya Mert,Ozkaya-Ahmadov Tevhide,Swain Brandi E.,Chu Chia-Heng,Asmare Norh,Civelekoglu OzgunORCID,Liu RuxiuORCID,Lee DohwanORCID,Tobia Sherry,Biliya Shweta,McDonald L. DeEtte,Nazha Bassel,Kucuk Omer,Sanda Martin G.,Benigno Benedict B.,Moreno Carlos S.ORCID,Bilen Mehmet A.,McDonald John F.,Sarioglu A. FatihORCID

Abstract

AbstractExtremely 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.

Funder

Georgia Institute of Technology

U.S. Department of Defense

Georgia Tech | Parker H. Petit Institute for Bioengineering and Bioscience

Emory University | Winship Cancer Institute

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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