Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells

Lin, Hsien-Chung; Zheng, Siyang; Williams, Anthony; Balić, Marija; Groshen, Susan; Scher, Howard I.; Fleisher, Martin; Stadler, Walter M.; Datar, Ram H.; Ye, Tai; Côté, Richard J.

doi:10.1158/1078-0432.ccr-10-1105

Cited by 419 publications

(395 citation statements)

References 17 publications

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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

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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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

139

104

View full text Add to dashboard Cite

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“…Thus, different devices based on cell filtration and centrifugal force have been recently developed. [9][10][11] Membrane-based filter systems, such as isolation by size of epithelial tumor cells (ISET), have demonstrated to be an efficient, inexpensive, and quick method for enriching CTCs. 12 A direct comparison of CellSearch and ISET for CTCs isolation demonstrated that ISET performed better than CellSearch in detecting CTCs in patients with metastatic prostate carcinoma and metastatic lung carcinoma.…”

Section: Detection and Enrichment Techniquesmentioning

confidence: 99%

Progress of Circulating Tumor Cells in Cancer Management

Zhang

Wang

Guan

et al. 2015

Technol Cancer Res Treat

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Circulating tumor cells are low-frequency cells that are shed into the peripheral bloodstream from a primary solid tumor and/or metastasis. Although these cells were recognized initially in 1869, it is only in the past 2 decades that they have been isolated for use as a surrogate biomarker to monitor response to therapy, evaluate prognosis, detect tumor mutations, assist in selecting personalized medicine, and enable earlier cancer diagnosis.

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“…2 Furthermore, circulating pancreatic cells exist in a subset of patients without cancer but with potentially cancerous pancreatic cystic lesions. 4 To obtain this information, CTCs have been successfully captured from blood samples through mechanical, 7 electromechanical 8 and immunoaffinity methods, 9-11 the last being the most common. However, challenges exist capturing subsets of CTCs that have reduced antigen expression, often associated with the epithelial to mesenchymal transition (EMT) 12 or acquired resistance to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Automated electrorotation shows electrokinetic separation of pancreatic cancer cells is robust to acquired chemotherapy resistance, serum starvation, and EMT

Lannin

Gruber

et al. 2016

Biomicrofluidics

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We used automated electrorotation to measure the cytoplasmic permittivity, cytoplasmic conductivity, and specific membrane capacitance of pancreatic cancer cells under environmental perturbation to evaluate the effects of serum starvation, epithelial-to-mesenchymal transition, and evolution of chemotherapy resistance which may be associated with the development and dissemination of cancer. First, we compared gemcitabine-resistant BxPC3 subclones with gemcitabine-naive parental cells. Second, we serum-starved BxPC3 and PANC-1 cells and compared them to untreated counterparts. Third, we induced the epithelial-to-mesenchymal transition in PANC-1 cells and compared them to untreated PANC-1 cells. We also measured the electrorotation spectra of white blood cells isolated from a healthy donor. The properties from fit electrorotation spectra were used to compute dielectrophoresis (DEP) spectra and crossover frequencies. For all three experiments, the median crossover frequency for both treated and untreated pancreatic cancer cells remained significantly lower than the median crossover frequency for white blood cells. The robustness of the crossover frequency to these treatments indicates that DEP is a promising technique for enhancing capture of circulating cancer cells. Published by AIP Publishing. [http://dx

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Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells

Cited by 419 publications

References 17 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

Progress of Circulating Tumor Cells in Cancer Management

Automated electrorotation shows electrokinetic separation of pancreatic cancer cells is robust to acquired chemotherapy resistance, serum starvation, and EMT

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