High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 13, 2022
- Source ID
- 10.1038/s41467-022-31009-9
Entities
People
- A Fatih Sarioglu
- Bassel Nazha
- Benedict B. Benigno
- Brandi E. Swain
- Carlos S Moreno
- Chia-heng Chu
- Jeong Hoon Lee
- John F. Mcdonald
- L. Deette Mcdonald
- Martin G. Sanda
- Mehmet A. Bilen
- Mert Boya
- Norh Asmare
- Omer Kucuk
- Ozgun Civelekoglu
- Ruxiu Liu
- Sherry Tobia
- Shweta Biliya
- Tevhide Ozkaya-ahmadov
Organizations
- Emory University
- Georgia Tech
- Parker H. Petit Institute for Bioengineering & Bioscience
- United States Department of Defense