scholarly journals An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 560
Author(s):  
Chaithanya Chelakkot ◽  
Jiyeon Ryu ◽  
Mi Young Kim ◽  
Jin-Soo Kim ◽  
Dohyeong Kim ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Nsclc Patient ◽  
Clinical Progression ◽  
Mcf7 Cells ◽  
Cytokeratin 18 ◽  
Multiple Biomarkers ◽  
Tyrosine Protein Kinase ◽  
Nsclc Patients

Here, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating tumor cells at a 90 μL/min flow rate when tested on blood spiked with epithelial cell adhesion molecule (EpCAM)-positive Michigan Cancer Foundation-7 (MCF7) cells. Clinical studies were performed using blood samples from non-small cell lung cancer (NSCLC) patients. Varying numbers (2 to 114) of CTCs were found in each NSCLC patient, and serial assessment of CTCs showed that the CTC count correlated with the clinical progression of the disease. The applicability of GenoCTC to different cell surface biomarkers was also validated in a cholangiocarcinoma patient using anti-EPCAM, anti-vimentin, or anti-tyrosine protein kinase MET (c-MET) antibodies. After EPCAM-, vimentin-, or c-MET-positive cells were isolated, CTCs were identified and enumerated by immunocytochemistry using anti-cytokeratin 18 (CK18) and anti-CD45 antibodies. Furthermore, we checked the protein expression of PDL1 and c-MET in CTCs. A study in a cholangiocarcinoma patient showed that the number of CTCs varied depending on the biomarker used, indicating the importance of using multiple biomarkers for CTC isolation and enumeration.

A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells

2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Automated Image Analysis ◽  
Rare Cancer ◽  
On Chip ◽  
Chip Analysis ◽  
Selection Of

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.

Ex VivoDetection of Circulating Tumor Cells from Whole Blood by Direct Nanoparticle Visualization

ACS Nano ◽  
2018 ◽  
Vol 12 (2) ◽  
pp. 1902-1909 ◽  
Author(s):  
Regivaldo G. Sobral-Filho ◽  
Lindsay DeVorkin ◽  
Sarah Macpherson ◽  
Andrew Jirasek ◽  
Julian J. Lum ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood

scholarly journals Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

Lab on a Chip ◽  
2019 ◽  
Vol 19 (20) ◽  
pp. 3427-3437 ◽  
Author(s):  
Chia-Heng Chu ◽  
Ruxiu Liu ◽  
Tevhide Ozkaya-Ahmadov ◽  
Mert Boya ◽  
Brandi E. Swain ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
3D Printed

A monolithic 3D-printed microfluidic device integrated with stacked layers of functionalized leukodepletion channels and microfiltration for the negative enrichment of circulating tumor cells directly from clinically relevant volumes of whole blood.

scholarly journals Nanostructured Surfaces to Target and Kill Circulating Tumor Cells While Repelling Leukocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Michael J. Mitchell ◽  
Carlos A. Castellanos ◽  
Michael R. King
Keyword(s):  
Cell Adhesion ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Halloysite Nanotubes ◽  
Breast Adenocarcinoma ◽  
Hematogenous Metastasis ◽  
Mcf7 Cells ◽  
Nanostructured Surfaces ◽  
Cancer Cell Death

Hematogenous metastasis, the process of cancer cell migration from a primary to distal location via the bloodstream, typically leads to a poor patient prognosis. Selectin proteins hold promise in delivering drug-containing nanocarriers to circulating tumor cells (CTCs) in the bloodstream, due to their rapid, force-dependent binding kinetics. However, it is challenging to deliver such nanocarriers while avoiding toxic effects on healthy blood cells, as many possess ligands that adhesively interact with selectins. Herein, we describe a nanostructured surface to capture flowing cancer cells, while preventing human neutrophil adhesion. Microtube surfaces with immobilized halloysite nanotubes (HNTs) and E-selectin functionalized liposomal doxorubicin (ES-PEG L-DXR) significantly increased the number of breast adenocarcinoma MCF7 cells captured from flow, yet also significantly reduced the number of captured neutrophils. Neutrophils firmly adhered and projected pseudopods on surfaces coated only with liposomes, while neutrophils adherent to HNT-liposome surfaces maintained a round morphology. Perfusion of both MCF7 cells and neutrophils resulted in primarily cancer cell adhesion to the HNT-liposome surface, and induced significant cancer cell death. This work demonstrates that nanostructured surfaces consisting of HNTs and ES-PEG L-DXR can increase CTC recruitment for chemotherapeutic delivery, while also preventing healthy cell adhesion and uptake of therapeutic intended for CTCs.

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