Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells

Harouaka, Ramdane; Zhou, Ming; Yeh, Yu‐Yan; Khan, Waleed J.; Das, Avisnata; Liu, Xin; Christ, Christine C.; Dicker, David T.; Baney, Tara; Kaifi, Jussuf T.; Belani, Chandra P.; Truica, Cristina I.; El‐Deiry, Wafik S.; Allerton, Jeffrey P.; Zheng, Shan

doi:10.1373/clinchem.2013.206805

Cited by 129 publications

(111 citation statements)

References 40 publications

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“…In contrast, the membrane filtration can provide size filtration by controlling pore size on the membrane. However, strong shear stress which is applied to cells during the filtration sometimes gives serious damage to cells, or it might give some clotting of cells on the membrane surface222324. Upon comparison of these methods, we can regard our method as an advanced MACS method which can cover size filtration function with maintaining all advantages of conventional MACS method, and our method can overcome all existing problems in conventional membrane filtration method.…”

Section: Discussionmentioning

confidence: 97%

Cup-Shaped Superparamagnetic Hemispheres for Size-Selective Cell Filtration

Kim

Terazono

2014

Sci Rep

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We propose a new method of size separation of cells exploiting precisely size-controlled hemispherical superparamagnetic microparticles. A three-layered structure of a 2-nm nickel layer inserted between 15-nm silicon dioxide layers was formed on polystyrene cast spheres by vapor deposition. The polystyrene was then removed by burning and the hemispherical superparamagnetic microparticles, “magcups”, were obtained. The standard target cells (CCRF-CEM, 12 ± 2 μm) were mixed with a set of different sizes of the fabricated magcups, and we confirmed that the cells were captured in the magcups having cavities larger than 15 μm in diameter, and then gathered by magnetic force. The collected cells were grown in a culture medium without any damage. The results suggest that this method is quick, simple and non-invasive size separation of target cells.

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Section: Discussionmentioning

confidence: 97%

Cup-Shaped Superparamagnetic Hemispheres for Size-Selective Cell Filtration

Kim

Terazono

2014

Sci Rep

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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: 94%

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

139

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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“…Multiple studies using microfiltration for CTC isolation have reported capturing CTC clusters (aka microemboli) (Desitter et al, 2011;Harouaka et al, 2014;Ilie et al, 2014;Vona et al, 2000). These reports indicate that CTC clusters stay intact when isolated with microfiltration methods, whereas other enrichment strategies may either fail to capture clusters or break them apart.…”

Section: Three-dimensional Microfiltration Systemsmentioning

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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Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells

Cited by 129 publications

References 40 publications

Cup-Shaped Superparamagnetic Hemispheres for Size-Selective Cell Filtration

Cup-Shaped Superparamagnetic Hemispheres for Size-Selective Cell Filtration

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

Circulating tumor cell technologies

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