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High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
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High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
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Journal Article
High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
2022
Overview
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.
Metastatic CTC clusters remain relatively unexplored due to the lack of optimized and practical technologies for their detection. Here the authors report Cluster-Wells to isolate CTC clusters in whole blood; they show this allows viable cluster retrieval for further molecular and functional analysis.
