Advances and critical concerns with the microfluidic enrichments of circulating tumor cells

Hyun, Kyung A.; Jung, Hyo Il

doi:10.1039/c3lc50582k

Cited by 108 publications

(93 citation statements)

References 56 publications

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“…Integration of microfluidic approaches with selective body fluid sampling could not only remove the need for sample processing operations on these devices, but could also help to address the challenge of rare event analysis. In the case of circulating tumor cell analysis, there is already a significant number of microfluidic devices available to isolate these cells from blood samples; 178,179 if they could be used to isolate these very rare cells from the entire blood volume of a patient, in a minimally invasive manner, this could significantly improve the clinical utility of these devices. Ferguson's study shows that microfluidic systems can indeed be integrated into body fluid sampling for real-time and continuous monitoring approaches, and we hope to see more demonstrations of this in the future, for a range of different classes of biomarkers.…”

Section: Emerging Trends and Future Opportunitiesmentioning

confidence: 99%

Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis

Corrie

Coffey

Islam

et al. 2015

Analyst

175

144

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Biosensors are being developed to provide rapid, quantitative, diagnostic information to clinicians in order to help guide patient treatment, without the need for centralised laboratory assays. The success of glucose monitoring is a key example of where technology innovation has met a clinical need at multiple levelsfrom the pathology laboratory all the way to the patient's home. However, few other biosensor devices are currently in routine use. Here we review the challenges and opportunities regarding the integration of biosensor techniques into body fluid sampling approaches, with emphasis on the point-of-care setting.

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Section: Emerging Trends and Future Opportunitiesmentioning

confidence: 99%

Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis

Corrie

Coffey

Islam

et al. 2015

Analyst

175

144

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“…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.…”

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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“…Many common methods for the enrichment of these rare cells have been previously reviewed, and a summary of these select techniques is shown in the Table. 102,103 Because many of these techniques have been reviewed elsewhere, [103][104][105][106][107][108] we will focus on novel CTC isolation techniques primarily using microfluidics that decrease CTC cell loss, increase recovery rates, use small volumes of blood, and enable the molecular analysis of individual CTCs. 109 Their current advantages and disadvantages are also reviewed.…”

Section: Novel Isolation Techniquesmentioning

confidence: 99%

“…In addition, size filtration-based approaches similar to the 2 reviewed here can have significant red and white blood cell contamination if the pores are plugged with CTCs. 109 This could hinder downstream genetic analysis by increasing the DNA background contamination.…”

Section: Novel Isolation Techniquesmentioning

confidence: 99%

Circulating Tumor Cells: A Window into Tumor Development and Therapeutic Effectiveness

2015

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Background Circulating tumor cells (CTCs) are an important diagnostic tool for understanding the metastatic process and the development of cancer. Methods This review covers the background, relevance, and potential limitations of CTCs as a measurement of cancer progression and how information derived from CTCs may affect treatment efficacy. It also highlights the difficulties of characterizing these rare cells due to the limited cell surface molecules unique to CTCs and each particular type of cancer. Results The analysis of cancer in real time, through the measure of the number of CTCs in a “liquid” biopsy specimen, gives us the ability to monitor the therapeutic efficacy of treatments and possibly the metastatic potential of a tumor. Conclusions Through novel and innovative techniques yielding encouraging results, including microfluidic techniques, isolating and molecularly analyzing CTCs are becoming a reality. CTCs hold promise for understanding how tumors work and potentially aiding in their demise.

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Advances and critical concerns with the microfluidic enrichments of circulating tumor cells

Cited by 108 publications

References 56 publications

Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis

Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis

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

Circulating Tumor Cells: A Window into Tumor Development and Therapeutic Effectiveness

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