Benchtop Technologies for Circulating Tumor Cells Separation Based on Biophysical Properties

Low, Wan Shi; Abas, Wan Abu Bakar Wan

doi:10.1155/2015/239362

Cited by 68 publications

(52 citation statements)

References 101 publications

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“…The cytoskeletal stiffness of CTCs is dynamically modified. This flexibility may facilitate their invasion to distal sites from the primary tumor and may confer their resistance to damage from fluid shear stress within the blood vessels during the metastatic process (21 ). These modifications in the stiffness alter the conservation of the membrane structure, which in turn affects their surface charge and electrical properties (21 ).…”

Section: Methods Based On Physical Propertiesmentioning

confidence: 99%

“…This flexibility may facilitate their invasion to distal sites from the primary tumor and may confer their resistance to damage from fluid shear stress within the blood vessels during the metastatic process (21 ). These modifications in the stiffness alter the conservation of the membrane structure, which in turn affects their surface charge and electrical properties (21 ). Various approaches have been used to exploit the differences in physical properties between tumor cells and blood cells as a means of enriching and separating CTCs from blood samples (Fig.…”

Section: Methods Based On Physical Propertiesmentioning

confidence: 99%

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Circulating Tumor Cells: A Review of Non–EpCAM-Based Approaches for Cell Enrichment and Isolation

et al. 2016

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International audienceBackground: Circulating tumor cells (CTCs) are biomarkers for non-invasively measuring the evolution of tumor genotypes during treatment and disease progression. Recent technical progress has made it possible to detect and characterize CTCs at the single-cell level in blood. Content: Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection since it fails to detect both carcinoma cells that undergo epithelial-mesenchymal transition (EMT), and CTCs of mesenchymal origin. Moreover, EpCAM expression has been found in patients with benign diseases. A large proportion of the current studies and reviews about CTCs describe EpCAM based methods, but there are evidences that not all tumor cells can be detected using this marker. Here we describe the most recent EpCAM-independent methods for enriching, isolating and characterizing CTCs, based on physical and biological characteristics, and point out their main advantages and disadvantages.Summary: CTCs offer an opportunity to obtain key biological information required for the development of personalized medicine. However there is no universal marker of these cells. To strengthen the clinical utility of CTCs, it is important to improve existing technologies and develop new, non-EpCAM based systems to enrich and isolate CTCs

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Section: Methods Based On Physical Propertiesmentioning

confidence: 99%

Section: Methods Based On Physical Propertiesmentioning

confidence: 99%

Circulating Tumor Cells: A Review of Non–EpCAM-Based Approaches for Cell Enrichment and Isolation

et al. 2016

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“…However, methods that rely on the assumption that CTCs are larger than nucleated blood cells are flawed, as tumor cells in different stages of the cell cycle, undergoing apoptosis, or in EMT may be smaller in size (59). In addition, the issue of CTC deformability is controversial, being difficult to characterize and lacking precision (61). Thus, the performance in clinical settings of current physical isolation methods is likely to be lower than predicted from model studies with tumor cell lines.…”

Section: New Techniques For Ctc Enrichment and Identificationmentioning

confidence: 99%

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

Hardingham

Grover

Winter

et al. 2015

Mol Med

124

104

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Circulating tumor cells (CTC) may be defined as tumor-or metastasis-derived cells that are present in the bloodstream. The CTC pool in colorectal cancer (CRC) patients may include not only epithelial tumor cells, but also tumor cells undergoing epithelial-mesenchymal transition (EMT) and tumor stem cells. A significant number of patients diagnosed with early stage CRC subsequently relapse with recurrent or metastatic disease despite undergoing "curative" resection of their primary tumor. This suggests that an occult metastatic disease process was already underway, with viable tumor cells being shed from the primary tumor site, at least some of which have proliferative and metastatic potential and the ability to survive in the bloodstream. Such tumor cells are considered to be responsible for disease relapse in these patients. Their detection in peripheral blood at the time of diagnosis or after resection of the primary tumor may identify those early-stage patients who are at risk of developing recurrent or metastatic disease and who would benefit from adjuvant therapy. CTC may also be a useful adjunct to radiological assessment of tumor response to therapy. Over the last 20 years many approaches have been developed for the isolation and characterization of CTC. However, none of these methods can be considered the gold standard for detection of the entire pool of CTC. Recently our group has developed novel unbiased inertial microfluidics to enrich for CTC, followed by identification of CTC by imaging flow cytometry. Here, we provide a review of progress on CTC detection and clinical significance over the last 20 years.

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“…8,9 Many emerging microfluidic technologies take advantage of cell size as a means for isolating CTCs, 10 which tend to be larger than their blood cell counterparts. 11 Strategies include the use of pores 12 or narrow channel constrictions 13 for microfiltration, micropillar arrays for deterministic lateral displacement, 14 or dean flow fractionation 15 in which inertial fluidic forces scale strongly with cell size. 16 Depending on the specific downstream applications, certain technologies may be favored over others since many have limitations with capture efficiency, sample purity, throughput, scalability, dilute output volume, cell damage, manually intensive procedures, or other impeding factors.…”

Section: Introductionmentioning

confidence: 99%

“…20 Although capture of CTCs in filter structures can depend on cell deformability and size, 11,13 there has been no conclusive study evaluating the mechanical properties of circulating tumor cells as they appear within the blood, in a manner independent of differences in size. In fact, because of cell deformability, many filtration reports require cell fixation prior to processing, preventing characterization of the in vivo biophysical state of CTCs.…”

Section: Introductionmentioning

confidence: 99%

Biophysical isolation and identification of circulating tumor cells

Che

Garon

et al. 2017

Lab Chip

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Isolation and enumeration of circulating tumor cells (CTCs) from blood is important for determining patient prognosis and monitoring treatment. Methods based on affinity to cell surface markers have been applied to both purify (via immunoseparation) and identify (via immunofluorescence) CTCs. However, variability of cell biomarker expression associated with tumor heterogeneity and evolution and cross-reactivity of antibody probes have long complicated CTC enrichment and immunostaining. Here we report a truly label-free high-throughput microfluidic approach to isolate, enumerate, and characterize the biophysical properties of CTCs on an integrated microfluidic device. Vortex-mediated Deformability Cytometry (VDC) consists of an initial vortex region which enriches for large CTCs, followed by release into a downstream hydrodynamic stretching region which deforms the cells. Visualization and quantification of cell deformation with a high-speed camera revealed populations of large (>15 μm diameter) and deformable (aspect ratio >1.2) CTCs from 16 stage IV lung cancer samples, that are clearly distinguished by increased deformability compared to contaminating blood cells and rare large cells isolated from healthy patients. VDC technology demonstrated a comparable positive detection rate of putative CTCs above healthy baseline (93.8%) with respect to standard immunofluorescence (71.4%). Automation allows full enumeration of CTCs from a 10mL vial of blood within <1 hr after sample acquisition, compared with 4+ hours with standard approaches. Moreover, cells are released into any collection vessel for further downstream analysis. VDC shows potential for accurate CTC enumeration without labels and confirms the unique highly deformable biophysical properties of large CTCs circulating in blood.

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Benchtop Technologies for Circulating Tumor Cells Separation Based on Biophysical Properties

Cited by 68 publications

References 101 publications

Circulating Tumor Cells: A Review of Non–EpCAM-Based Approaches for Cell Enrichment and Isolation

Circulating Tumor Cells: A Review of Non–EpCAM-Based Approaches for Cell Enrichment and Isolation

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

Biophysical isolation and identification of circulating tumor cells

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