Mitigation of Channel Clogging in a Microfluidic Device for Capturing Circulating Tumor Cells

2020 ◽  
Vol 14 (1) ◽  
pp. 109-116
Author(s):  
Tomoki Konishi ◽  
Yuki Jingu ◽  
Tatsuya Yoshizawa ◽  
Masaru Irita ◽  
Toshihiro Suzuki ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Propidium Iodide ◽  
Peripheral Blood ◽  
Lateral Displacement ◽  
Microfluidic Devices ◽  
Cell Detachment ◽  
Deterministic Lateral Displacement ◽  
Blood Specimen

Deterministic lateral displacement (DLD) based microfluidic devices have been developed for capturing circulating tumor cells (CTCs) from the peripheral blood. There was frequent and problematic channel clogging around the micro-post array formed on a microchannel of the device. In this study, various agents were dispersed into the blood specimen to avoid clogging. At first, platelet aggregation was considered to be the cause of the clogging, but even plasmin, which was assumed to decompose platelet aggregations, did not show obvious inhibition of the clogging. Then, enzymes used for cell detachment from tissue were examined and decomposition of the clogging residue was observed. Finally, dispersion of deoxyribonuclease into a blood specimen was found to be effective for the inhibition of clogging. The existence of DNA in the clogging residue was also confirmed by propidium iodide (PI) staining, suggesting DNA adhering to the micro-post.

scholarly journals Numerical Simulation of Separation of Circulating Tumor Cells from Blood Stream in Deterministic Lateral Displacement (DLD) Microfluidic Channel

2015 ◽  
Vol 32 (4) ◽  
pp. 463-471 ◽  
Author(s):  
F. Khodaee ◽  
S. Movahed ◽  
N. Fatouraee ◽  
F. Daneshmand
Keyword(s):  
Fluid Flow ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Flow Condition ◽  
Lateral Displacement ◽  
Microfluidic Devices ◽  
Blood Stream ◽  
Deterministic Lateral Displacement ◽  
Effective Design

AbstractDeterministic Lateral Displacement (DLD) microfluidic devices provide a reliable label-free separation method for detection of circulating tumor cells (CTCs) in blood samples based on their biophysical properties. In this paper, we proposed an effective design of the DLD microfluidic device for the CTC separation in the blood stream. A typical DLD array is designed and numerical simulations are performed to separate the CTC and leukocyte (white blood cells) in different fluid flow conditions. Fluid-Solid Interaction method is used to investigate the behaviour of these deformable cells in fluid flow. In this study, the effects of critical parameters affecting cell separation in the DLD microfluidic devices (e.g.flow condition, cell deformability, and stress) have been investigated. The obtained results show that unlike leukocytes, the CTC’s motion is independent of the flow condition and is laterally displaced even in higher Reynolds number. Larger cells (CTCs) cannot intercept the low-velocity fluid near the wall of the posts; thus, they move faster and become separated from leukocytes. To reduce the cellular stress during separation process, which causes increase of cell viability and more effective design of microfluidic device, the results obtained here may be used as a significant design parameter for the DLD fabrication.

Enhancing the Cell Viability in High Throughput Deterministic Lateral Displacement Separation of Circulating Tumor Cells

2019 ◽  
Author(s):  
Arian Aghilinejad ◽  
Christopher Landry ◽  
George Cha ◽  
Xiaolin Chen
Keyword(s):  
Reynolds Number ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
High Throughput ◽  
Cancer Metastasis ◽  
Lateral Displacement ◽  
Shear Stresses ◽  
Label Free ◽  
Deterministic Lateral Displacement ◽  
Reynolds Number Flow

Abstract Cancer is among a major health concerns all over the world. Cancer metastasis, which defines as the migration of malignant cells from original sites to distant organs, is the main reason of death due to cancer and there is growing evidence that Circulating Tumor Cells (CTCs) are responsible for initiating the metastasis. Due to the importance of these bioparticles in biotechnology and medicine, there is a growing interest to study and separate them through different techniques especially microfluidic label-free technologies. One such technology, termed Deterministic Lateral Displacement (DLD) has recently shown promising abilities to separate cells and particles of different sizes. However, DLD is a separation method that takes advantages of the predictable flow laminae of low Reynolds number (Re) fluid flow. In order to achieve higher device throughput, effects of higher Reynolds number flow on DLD device should be studied. Additionally, the higher flow rates would apply higher forces and shear stresses on the cells which threaten the cell’s viability. In this study, employing numerical simulation, the effect of high Re number on DLD device for separating cancer cells has been investigated. Specifically, we conducted force analysis and by focusing on the downstream gap distance between the posts, we improved the device which results in less cell deformation. Our developed numerical model and presented results lay the groundwork for design and fabrication of high-throughput DLD microchips for enhanced separation of CTCs.

Cascaded filter deterministic lateral displacement microchips for isolation and molecular analysis of circulating tumor cells and fusion cells

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Zongbin Liu ◽  
Yuqing Huang ◽  
Wenli Liang ◽  
Jing Bai ◽  
Hongtao Feng ◽  
...  
Keyword(s):  
Cancer Research ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Molecular Analysis ◽  
Lateral Displacement ◽  
Personalized Treatment ◽  
Blood Samples ◽  
Deterministic Lateral Displacement ◽  
Considerable Potential ◽  
Cascaded Filter

Precise isolation and analysis of circulating tumor cells (CTCs) from blood samples offer considerable potential for cancer research and personalized treatment. Currently, available CTCs isolation approaches remain challenging in the...

scholarly journals Molecular Detection of Peripheral Blood Breast Cancer mRNA Transcripts as a Surrogate Biomarker for Circulating Tumor Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74079 ◽  
Author(s):  
Adriana Lasa ◽  
Arnal Garcia ◽  
Carmen Alonso ◽  
Pilar Millet ◽  
Mónica Cornet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Molecular Detection ◽  
Mrna Transcripts

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.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

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