Size-Selective Microcavity Array for Rapid and Efficient Detection of Circulating Tumor Cells

Hosokawa, Masahito; Hayata, Taishi; Fukuda, Yorikane; Arakaki, Atsushi; Yoshino, Tomoko; Tanaka, Tsuyoshi; Matsunaga, Tadashi

doi:10.1021/ac101222x

Cited by 315 publications

(341 citation statements)

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“…Furthermore, the randomly distributed holes are prone to significant coalescence of two or more holes allowing tumor cells to escape from the filter. More recent studies have shown that a variety of microfabrication techniques could be used to manufacture filters of different hole-types and densities [36][37][38][39][40][41][42][43][44][45] , but none of them were able to meet the critical requirements for both clinical application and fundamental studies. …”

mentioning

confidence: 99%

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

137

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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mentioning

confidence: 99%

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

137

104

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“…These authors successfully achieved a significant correlation between the numbers of CACs and the presence of cancer. In order to improve efficient detection of tumor cells from peripheral blood of patients with cancer, Hosokawa et al [99] have developed a microfluidic device equipped with a size-selective microcavity array which can specifically separate tumor cells from in the bloodstream on the basis of differences in the size and deformability between tumor and hematologic cells. The cells recovered on the microcavity array were further processed for image-based immunophenotypic analysis using a fluorescence microscope.…”

Section: Circulating Dna Versus Circulating Tumor Cells Techniquementioning

confidence: 99%

Circulating DNA as a Biomarker for Early Detection of Cancer: A Brief Update with an Emphasis on Lung Cancer~!2010-06-09~!2010-08-03~!2010-09-06~!

Cabral¹

2010

TOLCJ

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Abstract:In most cases, early detection and treatment of cancer are prerequisites for full recovery. However, its early detection continues to be extremely difficult since its characteristic symptoms rarely manifest at the onset of disease. The development of highly sensitive, specific biomarkers also capable of reflecting pathological changes is, therefore, of the upmost importance. Lung cancer, for example, is most frequently diagnosed during the late metastatic stage so that, as a result, malignant neoplasms in the lung are among the leading causes of cancer-related deaths worldwide. Circulating DNA is a non-invasive diagnostic assay that has been greatly improved for the purposes of diagnosis, prognosis, and treatment of cancer. In the current review, we discuss recent data concerning circulating tumor-derived DNA as a tool for early detection, diagnosis, and follow-up. Given the scope of this review, the focus will be on lung cancer, one of the most prolific and lethal cancers affecting humanity today.

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Section: Introductionmentioning

confidence: 99%

Rational Design of Materials Interface for Efficient Capture of Circulating Tumor Cells

Chandran

Lim

et al. 2015

Advanced Science

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Originating from primary tumors and penetrating into blood circulation, circulating tumor cells (CTCs) play a vital role in understanding the biology of metastasis and have great potential for early cancer diagnosis, prognosis and personalized therapy. By exploiting the specific biophysical and biochemical properties of CTCs, various material interfaces have been developed for the capture and detection of CTCs from blood. However, due to the extremely low number of CTCs in peripheral blood, there exists a need to improve the efficiency and specificity of the CTC capture and detection. In this regard, a critical review of the numerous reports of advanced platforms for highly efficient and selective capture of CTCs, which have been spurred by recent advances in nanotechnology and microfabrication, is essential. This review gives an overview of unique biophysical and biochemical properties of CTCs, followed by a summary of the key material interfaces recently developed for improved CTC capture and detection, with focus on the use of microfluidics, nanostructured substrates, and miniaturized nuclear magnetic resonance‐based systems. Challenges and future perspectives in the design of material interfaces for capture and detection of CTCs in clinical applications are also discussed.

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Size-Selective Microcavity Array for Rapid and Efficient Detection of Circulating Tumor Cells

Cited by 315 publications

References 32 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 DNA as a Biomarker for Early Detection of Cancer: A Brief Update with an Emphasis on Lung Cancer~!2010-06-09~!2010-08-03~!2010-09-06~!

Rational Design of Materials Interface for Efficient Capture of Circulating Tumor Cells

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