Fast enrichment and detection of circulating tumor cells from large volumes of whole blood of breast cancer patients utilizing a functionalized bioaffinity <scp>CTC</scp> filtration membrane

Circulating tumor cells (CTCs) are valuable liquid biopsy analytes as they facilitate an in-depth characterization of disseminated tumors by a simple blood draw. Most CTC assays can only process limited blood volumes, potentially hampering the detection of cells of very low frequency, such as CTCs. Here, we introduce a novel, functionalized nickel filtration membrane, facilitating rapid enrichment of CTCs from various volumes of blood up to 40 mL and leukapheresis products. We validated this assay with different cancer cell lines and compared the performance of our new assay with that of the FDA-cleared CellSearch® system. Performing a comparative analysis of 20 blood samples from patients with metastatic breast cancer, CTCs were found in 19/20 patients (95%), combining the results of both CTC enrichment assays. CTC counts/7.5 mL of blood ranged from 0 to 7280 (CTC filtration membrane) and 0 to 17,190 (CellSearch®). Applying the clinically relevant cut-off of ≥5 CTCs/7.5 mL of blood, 19/20 samples processed with our CTC filter were categorized identically to those analyzed with the CellSearch® system. Furthermore, the filtration time of 40 s for 7.5 mL of blood represents an important advantage of our system, compared to other systems. Importantly, we also demonstrated the feasibility of processing blood samples of up to 40 mL or 2 × 10<sup>8</sup> nucleated blood cells in 2.5 min. Overall, our new system provides the advantage of performing ultra-rapid enrichment of CTCs and upscaling the volume of blood that can be analyzed, which opens a new avenue for studies on CTC biology.

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Publication Details

Journal
International Journal of Cancer
Published
2025-10-27
DOI
https://doi.org/10.1002/ijc.70216
Primary Topic
Cancer Cells and Metastasis
Type
article
Field-Weighted Citation Impact
0.00

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article

Fast enrichment and detection of circulating tumor cells from large volumes of whole blood of breast cancer patients utilizing a functionalized bioaffinity CTC filtration membrane

M. Netkova-Heintzen, Anne Pradines, René Werner, Parinaz Mossahebi Mohammadi et al.
International Journal of Cancer
Cancer Cells and Metastasis
article

Fast enrichment and detection of circulating tumor cells from large volumes of whole blood of breast cancer patients utilizing a functionalized bioaffinity CTC filtration membrane

M. Netkova-Heintzen, Anne Pradines, René Werner, Parinaz Mossahebi Mohammadi, Laura L. Michel, Andreas Schneeweiss, Leonie Ott, Maria Geffken, Sven Peine, Cornelia Coith, Marc Zinggeler, Nikolas Hendrik Stoecklein, Klaus Pantel, Thomas Maximilian Deutsch, Nathan Bentley, Verena Thewes, Laura Keller, Sabine Riethdorf, Andreas Trumpp, Volkmar Mueller, Elena Laakmann, Corinna Güsmer, Jürgen Rühe, Hümeyra Husseini‐Wüsthoff, Malte Löptien, Thomas Brandtstetter, Jakoba Heidler
article en

Abstract

Circulating tumor cells (CTCs) are valuable liquid biopsy analytes as they facilitate an in-depth characterization of disseminated tumors by a simple blood draw. Most CTC assays can only process limited blood volumes, potentially hampering the detection of cells of very low frequency, such as CTCs. Here, we introduce a novel, functionalized nickel filtration membrane, facilitating rapid enrichment of CTCs from various volumes of blood up to 40 mL and leukapheresis products. We validated this assay with different cancer cell lines and compared the performance of our new assay with that of the FDA-cleared CellSearch® system. Performing a comparative analysis of 20 blood samples from patients with metastatic breast cancer, CTCs were found in 19/20 patients (95%), combining the results of both CTC enrichment assays. CTC counts/7.5 mL of blood ranged from 0 to 7280 (CTC filtration membrane) and 0 to 17,190 (CellSearch®). Applying the clinically relevant cut-off of ≥5 CTCs/7.5 mL of blood, 19/20 samples processed with our CTC filter were categorized identically to those analyzed with the CellSearch® system. Furthermore, the filtration time of 40 s for 7.5 mL of blood represents an important advantage of our system, compared to other systems. Importantly, we also demonstrated the feasibility of processing blood samples of up to 40 mL or 2 × 10<sup>8</sup> nucleated blood cells in 2.5 min. Overall, our new system provides the advantage of performing ultra-rapid enrichment of CTCs and upscaling the volume of blood that can be analyzed, which opens a new avenue for studies on CTC biology.

International Journal of CancerVol. 158(6)
Swiss Center for Electronics and Microtechnology (Switzerland) (CH), Universität Hamburg (DE), University of Freiburg (DE), German Cancer Research Center (DE), Heidelberg University (DE), University Hospital Heidelberg (DE), Düsseldorf University Hospital (DE), University Medical Center Hamburg-Eppendorf (DE), National Center for Tumor Diseases (DE), Institut Claudius Regaud (FR), DKFZ-ZMBH Alliance (DE), Heinrich Heine University Düsseldorf (DE)
Erich und Gertrud Roggenbuck-Stiftung, Bundesministerium für Bildung und Forschung, Deutsche Krebshilfe
Openalex Percentile: Top 58%
Cancer Cells and Metastasis
DOIOpen Access PDFOpenAlex
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