Abstract 2389: A microfluidic system for the selection of circulating tumor cells that utilizes both affinity and size capture technologies

Author(s):  
Denis Smirnov ◽  
Keith Merdek ◽  
Kam Sprott ◽  
Alison Skelley ◽  
Richard Huang ◽  
...  
2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.


2018 ◽  
Vol 115 (40) ◽  
pp. 9986-9991 ◽  
Author(s):  
Manjima Dhar ◽  
Jeffrey Nam Lam ◽  
Tonya Walser ◽  
Steven M. Dubinett ◽  
Matthew B. Rettig ◽  
...  

Tumor cells are hypothesized to use proteolytic enzymes to facilitate invasion. Whether circulating tumor cells (CTCs) secrete these enzymes to aid metastasis is unknown. A quantitative and high-throughput approach to assay CTC secretion is needed to address this question. We developed an integrated microfluidic system that concentrates rare cancer cells >100,000-fold from 1 mL of whole blood into ∼50,000 2-nL drops composed of assay reagents within 15 min. The system isolates CTCs by size, exchanges fluid around CTCs to remove contaminants, introduces a matrix metalloprotease (MMP) substrate, and encapsulates CTCs into microdroplets. We found CTCs from prostate cancer patients possessed above baseline levels of MMP activity (1.7- to 200-fold). Activity of CTCs was generally higher than leukocytes from the same patient (average CTC/leukocyte MMP activity ratio, 2.6 ± 1.5). Higher MMP activity of CTCs suggests active proteolytic processes that may facilitate invasion or immune evasion and be relevant phenotypic biomarkers enabling companion diagnostics for anti-MMP therapies.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yoon Seok Suh ◽  
Jae Young Joung ◽  
Sung Han Kim ◽  
Ho Kyung Seo ◽  
Jinsoo Chung ◽  
...  

Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC. Liquid biopsy using CTCs has been gaining attention as a minimal invasive tool for investigation of biomarkers and for prognosis and assessment of response to therapies in patients with PC. Because of the lower invasiveness of liquid biopsy using CTCs, it can be performed more frequently; accordingly, personalized disease status can be successively determined at serial time points. CTC analysis enables detection of genomic alterations, which is drug-targetable, and it is a potential tool for monitoring response to therapeutic agents in patients with PC. This review focuses on the characteristics, technologies for analysis, and advantages and disadvantages of CTCs as a liquid biopsy tool and their application in PC. Finally, we propose future directions of CTCs.


2012 ◽  
Vol 319 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Bianca Mostert ◽  
Jaco Kraan ◽  
Anieta M. Sieuwerts ◽  
Petra van der Spoel ◽  
Joan Bolt-de Vries ◽  
...  

2020 ◽  
Vol 9 (4) ◽  
pp. 1206 ◽  
Author(s):  
Arvind Iyer ◽  
Krishan Gupta ◽  
Shreya Sharma ◽  
Kishore Hari ◽  
Yi Fang Lee ◽  
...  

We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e22023-e22023
Author(s):  
Sohan Lal Punia ◽  
LIntao Bi ◽  
Mehmet Akif Turker ◽  
Jin Sung Jang ◽  
Michael B Campion ◽  
...  

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