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Updated: Sep 8, 2025
Clinical Microfluidic Chip Platform for the Isolation of Versatile Circulating Tumor Cells
Published on: October 13, 2023
High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
Mert Boya1, Tevhide Ozkaya-Ahmadov1, Brandi E Swain1
1School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
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.
Insights
New Cluster-Wells technology efficiently isolates rare circulating tumor cell (CTC) clusters from blood. This breakthrough enables better research into CTC clusters as cancer metastasis precursors.
Area of Science:
- Oncology
- Biotechnology
- Medical Diagnostics
Background:
- Circulating tumor cell (CTC) clusters are rare but highly metastatic precursors.
- Existing technologies struggle to detect fragile CTC clusters or lack scalability.
- Current methods often focus on single CTCs, overlooking the significance of clusters.
Purpose of the Study:
- To introduce a novel technology, Cluster-Wells, for efficient and sensitive isolation of CTC clusters.
- To overcome the limitations of existing technologies in capturing and analyzing CTC clusters.
- To enable routine isolation and research of CTC clusters for cancer management.
Main Methods:
- Developed Cluster-Wells combining membrane filtration and microfluidic chip technology.
- Physically arrested CTC clusters in >100,000 microwells using unprocessed whole blood.
- Achieved high throughput isolation (>25 mL/h) and retrieval of viable CTC clusters.
Main Results:
- Successfully isolated CTC clusters (2-100+ cells) from prostate and ovarian cancer patients.
- Demonstrated the technology's ability to capture virtually all clusters present.
- Analyzed a subset of isolated CTC clusters using RNA sequencing.
Conclusions:
- Cluster-Wells technology provides a scalable and practical solution for CTC cluster isolation.
- This method facilitates the study of CTC clusters' role in cancer metastasis.
- Routine isolation of CTC clusters will advance research and potentially improve cancer patient management.
