Circulating Tumor Cell Enrichment Based on Physical Properties

Harouaka, Ramdane; Nisic, Merisa; Zheng, Shan

doi:10.1177/2211068213494391

Cited by 133 publications

(95 citation statements)

References 151 publications

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“…(2) leads to a transfilter pressure of 24 , 32 (10 , 14) Pa, which means that the transfilter pressure of conical holes is one order of magnitude lower than that of 30 mm thick cylindrical-holes. Such a decrease of transfilter pressure can lead to a significant increase of the cell viability [46][47][48][49] , proving again the advantage of conical-hole filters. Moreover, such a small transfilter pressure will remain the same during filtration if the clearance of the filter is efficient.…”

Section: Dp~3mentioning

confidence: 95%

Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells

Tang

Shi

et al. 2014

Sci Rep

136

104

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Capture of circulating tumor cells (CTCs) from peripheral blood of cancer patients has major implications for metastatic detection and therapy analyses. Here we demonstrated a microfluidic device for high efficiency and high purity capture of CTCs. The key novelty of this approach lies on the integration of a microfilter with conical-shaped holes and a micro-injector with cross-flow components for size dependent capture of tumor cells without significant retention of non-tumor cells. Under conditions of constant flow rate, tumor cells spiked into phosphate buffered saline could be recovered and then cultured for further analyses. When tumor cells were spiked in blood of healthy donors, they could also be recovered at high efficiency and high clearance efficiency of white blood cells. When the same device was used for clinical validation, CTCs could be detected in blood samples of cancer patients but not in that of healthy donors. Finally, the capture efficiency of tumor cells is cell-type dependent but the hole size of the filter should be more closely correlated to the nuclei size of the tumor cells. Together with the advantage of easy operation, low-cost and high potential of integration, this approach offers unprecedented opportunities for metastatic detection and cancer treatment monitoring.C irculating tumor cells (CTCs) in peripheral blood of cancer patients are reliable biomarkers for metastatic detection and treatment monitoring. The challenge is to capture them with a high efficiency and high purity, despite their extreme rarity and high phenotype heterogeneity [1][2][3][4][5][6][7][8][9][10] . Currently, two approaches are in competition, depending on whether or not the capture is affinity-based. The affinity-based capture relies on immunochemical interaction between magnetic beads [11][12][13][14][15][16] or patterned structures [17][18][19][20] and tumor cells that express special surface markers such as EpCAM, an epithelial cell adhesion molecule over expressed by majority of tumor cells. These methods are efficient for capturing CTCs of epithelial phenotypes but not applicable to those with down-regulated or lost epithelial markers. Indeed, it is known that tumor cells of epithelial origin may undergo epithelial to mesenchymal transition 21,22 . In contrast, the non-affinity methods, including centrifuging deflection [23][24][25][26][27] , dielectrophoretic separation [28][29][30] and size-based filtration 12,[31][32][33][34][35][36][37][38][39][40][41][42][43][44] , are able to isolate both epithelial and mesenchymal phenotypes, which are more appropriate for analyses of tumor heterogeneity, tumor drug resistance, etc. However, these approaches are technologically biased and it is often difficult to reach a trade-off between capture efficiency, purity and cell viability which are all important criteria for both fundamental and clinical studies. For example, the size-based filtration has been developed for more than several decades but the most of reported results were obtained by using track-etche...

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Section: Dp~3mentioning

confidence: 95%

Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells

Tang

Shi

et al. 2014

Sci Rep

136

104

View full text Add to dashboard Cite

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“…Size-based CTC enrichment technologies function on the precedent that CTCs generally exhibit a larger morphology than leukocytes. Multiple texts have reported sizes for leukocytes and other blood cells, and Harouaka et al provide a detailed summary of reported sizes for tumor cells and blood cells in their review (Harouaka et al, 2013). CTCs and white blood cells collected using a label-free microfluidic technology ranged from 12e25 mm and 8e14 mm in diameter, respectively (Sollier et al, 2014).…”

Section: Size Of Tumor Cellsmentioning

confidence: 99%

Circulating tumor cell technologies

2016

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Cancer CTC capture CTC clustersImmunoaffinity enrichment A B S T R A C TCirculating tumor cells, a component of the "liquid biopsy", hold great potential to transform the current landscape of cancer therapy. A key challenge to unlocking the clinical utility of CTCs lies in the ability to detect and isolate these rare cells using methods amenable to downstream characterization and other applications. In this review, we will provide an overview of current technologies used to detect and capture CTCs with brief insights into the workings of individual technologies. We focus on the strategies employed by different platforms and discuss the advantages of each. As our understanding of CTC biology matures, CTC technologies will need to evolve, and we discuss some of the present challenges facing the field in light of recent data encompassing epithelial-to-mesenchymal transition, tumor-initiating cells, and CTC clusters.

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“…small cell lung carcinoma of 7.2-10 microns) and blood type cancers (e.g. leukemia cells of 8.9-15.3 microns) [10,11]. Furthermore, blood type cancer cells don't express the EpCAM markers, and in cancer cells undergoing normal morphogenetic processes, also known as epithelial mesenchymal transition (EMT), which can lead to loss or gain of tumour markers including EpCAM markers [12].…”

Section: Introductionmentioning

confidence: 99%

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

2017

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IntroductionCirculating Tumour Cells (CTC) provide a biomarker for cancer prognosis and treatment effectiveness, whereby an increase in CTC count is associated with cancer progression, shorter progression free survival, and shorter overall survival compared to a decrease in CTC count [1,2]. In a group of 177 women with metastatic breast cancer, CTC count was directly related to disease progression and survival, whereby a CTC count of less than 0.7 CTC/ml (5 CTC in 7.5 ml of whole blood) had a longer progression free survival and overall survival compared to a CTC count of more than 0.7 CTC/ml (median progression-free survival 2.7 months versus 7.0 months, p<0.001), and median overall survival (10.1 months versus >18 months, p<0.001) [1]. Furthermore, the type of CTC cells, either single cells or CTC clusters, are a prognostic predictor of metastasizing potential and overall survival, with a hazard ratio of 14.5 (p<0.001) for ≥ 3-cell CTC clusters compared to no CTC [3].Presence of CTC has also been associated with early carcinogenesis and risk of cancer [4]. In a study of cancer-free patients with chronic obstructive pulmonary disease (COPD), CTC were detected in 3% of the patients, who developed lung cancer within 1-4 years after CTC screening.Several technologies have been developed to identify CTC, including the Isolation-by-Size-of-Epithelial-Tumour (ISET) technique (Rarecells, France) [5], which involves blood filtration, and analysis by microscopy using standard histo-pathological/ cyto-morphological criteria [6,7]. Blood is treated to lyse red blood cells, and remaining rare cells, including CTC and inflammatory (white blood) cells, are then enriched on a filter, stained and analysed by standard cytological microscopy. The ISET technology allows direct identification of CTC, independent of the presence of tumour markers [7]. AbstractBackground: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria.

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Circulating Tumor Cell Enrichment Based on Physical Properties

Cited by 133 publications

References 151 publications

Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells

Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells

Circulating tumor cell technologies

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

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