Interactions Between Circulating Tumor Cells and Aptamer-Functionalized Microposts in a Flow

2017 ◽  
Author(s):  
Kangfu Chen ◽  
Teodor Georgiev ◽  
Z. Hugh Fan
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Blood Cells ◽  
Volume Ratio ◽  
Microfluidic Devices ◽  
Cancer Prognosis ◽  
Device Performance ◽  
Simulation Methodology ◽  
Geometry Design

Circulating Tumor Cells (CTCs) have been considered as important biomarkers for cancer prognosis and treatment. However, there are only tens of CTCs in one billion of healthy blood cells. This CTC rarity challenge has been addressed by microfluidics technology that sheds light on efficient CTC detection and isolation. Using antibodies or aptamers to capture CTCs is one of the strategies for CTC isolation. A lot of work has been carried out to improve CTC capture efficiency and purity (i.e., specificity). The main consideration to optimize microfluidic device performance includes increasing surface-area-to-volume ratio and reducing shear stress, both of which are closely related to the interaction between CTCs and the microfluidic device. Here we report a detailed study on the interactions between CTCs and aptamer-functionalized microposts in a microfluidic device. We have evaluated the distribution of captured CTCs around a micropost. In addition, simulation was conducted to model CTC capture patterns around microposts. We found the simulated CTC capture pattern largely agree with the experimental results. The simulation methodology could be applicable for other affinity-based CTC isolation devices and approaches. The goal of the study is to improve the microfluidic device performance and provide a rapid and economical way to optimize the geometry design of the microfluidic devices for CTC isolation.

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.

scholarly journals Enrichment of Circulating Tumor Cells from Whole Blood Using a Microfluidic Device for Sequential Physical and Magnetophoretic Separations

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 481 ◽  
Author(s):  
Jusin Lee ◽  
Onejae Sul ◽  
Seung-Beck Lee
Keyword(s):  
Specific Surface ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
Blood Cells ◽  
Magnetic Beads ◽  
Separation Efficiency ◽  
White Blood Cells

Based on their high clinical potential, the isolation and enrichment of rare circulating tumor cells (CTCs) from peripheral blood cells has been widely investigated. There have been technical challenges with CTC separation methods using solely cancer-specific surface molecules or just using physical properties of CTCs, as they may suffer from heterogeneity or lack of specificity from overlapping physical characteristics with leukocytes. Here, we integrated an immunomagnetic-based negative enrichment method that utilizes magnetic beads attached to leukocyte-specific surface antigens, with a physical separation method that utilizes the distinct size and deformability of CTCs. By manipulating the pressure distribution throughout the device and balancing the drag and magnetic forces acting on the magnetically labeled white blood cells (WBCs), the sequential physical and magnetophoretic separations were optimized to isolate intact cancer cells, regardless of heterogeneity from whole blood. Using a breast cancer cell line in whole blood, we achieved 100% separation efficiency for cancer cells and an average of 97.2% for WBCs, which resulted in a 93.3% average separation purity. The experimental results demonstrated that our microfluidic device can be a promising candidate for liquid biopsy and can be a vital tool for aiding future cancer research.

A PLGA nanofiber microfluidic device for highly efficient isolation and release of different phenotypic circulating tumor cells based on dual aptamers

2021 ◽  
Author(s):  
Zeen Wu ◽  
Yue Pan ◽  
Zhili Wang ◽  
Pi Ding ◽  
Tian Gao ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Microfluidic Devices ◽  
Highly Efficient

Dual aptamer-modified PLGA nanofiber-based microfluidic devices were fabricated to achieve the highly efficient isolation and specific release of epithelial and mesenchymal CTCs.

Emerging Microfluidic Technologies for the Detection of Circulating Tumor Cells and Fetal Nucleated Red Blood Cells

2021 ◽  
Vol 4 (2) ◽  
pp. 1140-1155
Author(s):  
Xiaoyun Wei ◽  
Keke Chen ◽  
Shishang Guo ◽  
Wei Liu ◽  
Xing-Zhong Zhao
Keyword(s):  
Red Blood Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Blood Cells ◽  
Nucleated Red Blood Cells

scholarly journals Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1385
Author(s):  
Hyeon-Yeol Cho ◽  
Jin-Ha Choi ◽  
Joungpyo Lim ◽  
Sang-Nam Lee ◽  
Jeong-Woo Choi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Cancer ◽  
Cancer Prognosis ◽  
Optical Biosensors ◽  
Diagnosis And Prognosis ◽  
Noise Factors ◽  
Prediction Of Relapse

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

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 Cancer Diagnostics: Visual Quantitative Detection of Circulating Tumor Cells with Single‐Cell Sensitivity Using a Portable Microfluidic Device (Small 14/2019)

Small ◽  
2019 ◽  
Vol 15 (14) ◽  
pp. 1970075
Author(s):  
Mahlet Fasil Abate ◽  
Shasha Jia ◽  
Metages Gashaw Ahmed ◽  
Xingrui Li ◽  
Li Lin ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Cancer Diagnostics ◽  
Quantitative Detection ◽  
Cell Sensitivity

scholarly journals Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Micromachines ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 774 ◽  
Author(s):  
Jie Cheng ◽  
Yang Liu ◽  
Yang Zhao ◽  
Lina Zhang ◽  
Lingqian Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Human Peripheral Blood ◽  
Microfluidic Devices ◽  
Detection Sensitivity ◽  
Cell Capture ◽  
Primary Tumors ◽  
Downstream Analysis

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

scholarly journals Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1659 ◽  
Author(s):  
Verena Martini ◽  
Sylvia Timme-Bronsert ◽  
Stefan Fichtner-Feigl ◽  
Jens Hoeppner ◽  
Birte Kulemann
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Markers ◽  
Cancer Prognosis ◽  
Detection Methods ◽  
Ductal Adenocarcinoma ◽  
Detection Tool ◽  
The Usa ◽  
New Biomarkers

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

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