Technologies for label-free separation of circulating tumor cells: from historical foundations to recent developments

Jin, Chao; McFaul, Sarah M.; Duffy, Simon P.; Deng, Xiaoyan; Tavassoli, Peyman; Black, Peter C.; Ma, Hongshen

doi:10.1039/c3lc50625h

Cited by 178 publications

(158 citation statements)

References 109 publications

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“…We can deduce that, thanks to thick C-PDMS electrodes, DEP capture throughput can be increased while keeping a large capture yield. This yield is in the same order of magnitude as previously published works 42 where yield ranges from 60 to 96% and flow rates ranges from 6 ll/h to 1 ml/h.…”

Section: -9supporting

confidence: 74%

Dielectrophoretic capture of low abundance cell population using thick electrodes

et al. 2015

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Enrichment of rare cell populations such as Circulating Tumor Cells (CTCs) is a critical step before performing analysis. This paper presents a polymeric microfluidic device with integrated thick Carbon-PolyDimethylSiloxane composite (C-PDMS) electrodes designed to carry out dielectrophoretic (DEP) trapping of low abundance biological cells. Such conductive composite material presents advantages over metallic structures. Indeed, as it combines properties of both the matrix and doping particles, C-PDMS allows the easy and fast integration of conductive microstructures using a soft-lithography approach while preserving O 2 plasma bonding properties of PDMS substrate and avoiding a cumbersome alignment procedure. Here, we first performed numerical simulations to demonstrate the advantage of such thick C-PDMS electrodes over a coplanar electrode configuration. It is well established that dielectrophoretic force (F DEP ) decreases quickly as the distance from the electrode surface increases resulting in coplanar configuration to a low trapping efficiency at high flow rate. Here, we showed quantitatively that by using electrodes as thick as a microchannel height, it is possible to extend the DEP force influence in the whole volume of the channel compared to coplanar electrode configuration and maintaining high trapping efficiency while increasing the throughput. This model was then used to numerically optimize a thick C-PDMS electrode configuration in terms of trapping efficiency. Then, optimized microfluidic configurations were fabricated and tested at various flow rates for the trapping of MDA-MB-231 breast cancer cell line. We reached trapping efficiencies of 97% at 20 ll/h and 78.7% at 80 ll/h, for 100 lm thick electrodes. Finally, we applied our device to the separation and localized trapping of CTCs (MDA-MB-231) from a red blood cells sample (concentration ratio of 1:10). V C 2015 AIP Publishing LLC.

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Section: -9supporting

confidence: 74%

Dielectrophoretic capture of low abundance cell population using thick electrodes

et al. 2015

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“…Several reviews have discussed the various CTC enrichment and detection technologies (7,(9)(10)(11)(12). Table 1 presents an updated list of CTC assays that have been used to test patient samples within the past 5 years, along with their commercialization status.…”

Section: Ctc Enrichment and Detection Technologiesmentioning

confidence: 99%

Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility

Ignatiadis

Lee

Jeffrey

2015

Clinical Cancer Research

316

252

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Recent technological advances have enabled the detection and detailed characterization of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) in blood samples from patients with cancer. Often referred to as a "liquid biopsy," CTCs and ctDNA are expected to provide real-time monitoring of tumor evolution and therapeutic efficacy, with the potential for improved cancer diagnosis and treatment. In this review, we focus on these opportunities as well as the challenges that should be addressed so that these tools may eventually be implemented into routine clinical care.

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“…[22][23][24] The capture, isolation and enrichment of non-adherent abnormal CTC are based on their difference from hematologic cells in size and biophysical deformities such as such as shape, stiffness and electrical polarizability. [13][14][15][16][17][18][25][26][27][28][29] Many studies have reported that tumor cells are larger in size as compared to hematologic cells and this difference accounts for the…”

Section: Introductionmentioning

confidence: 99%

Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software

Shashni

Ariyasu

Takeda

et al. 2018

Biological & Pharmaceutical Bulletin

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SummaryDetection of anomalous cells such as cancer cells from normal blood cells has the potential to contribute greatly to cancer diagnosis and therapy. Conventional methods for the detection of cancer cells are usually tedious and cumbersome. Herein, we report on the use of a particle size analyzer for the convenient size-based differentiation of cancer cells from normal cells. Measurements made using a particle size analyzer revealed that size parameters for cancer cells are significantly greater (e.g., inner diameter and width) than the corresponding values for normal cells (white blood cells (WBC), lymphocytes and splenocytes), with no significant difference in shape parameters (e.g., circularity and convexity). The inner diameter of many cancer cell lines is greater than 10 μm, in contrast to normal cells. For the detection of WBC having similar size to that of cancer cells, we developed a PC software "Cancer Cell Finder" that differentiates them from cancer cells based on brightness inflection points on a cell surface. Furthermore, the aforementioned method was validated for cancer cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse xenograft model) and circulating tumor cell cluster-like particles in the cat and dog (diagnosed with cancer) blood samples. These results provide insights into the possible applicability of the use of a particle size analyzer in conjunction with PC software for the convenient detection of cancer cells in experimental and clinical samples for theranostics.

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Technologies for label-free separation of circulating tumor cells: from historical foundations to recent developments

Cited by 178 publications

References 109 publications

Dielectrophoretic capture of low abundance cell population using thick electrodes

Dielectrophoretic capture of low abundance cell population using thick electrodes

Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility

Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software

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