Capture and Release of Cancer Cells by Combining On-Chip Purification and Off-Chip Enzymatic Treatment

Yu, Xiaolei; Wang, Bingrui; Zhang, Nangang; Yin, Changqing; Chen, Hao; Zhang, Lingling; Cai, Bo; He, Zhaobo; Rao, Lang; Liu, Wei; Wang, Xinghuan; Guo, Shishang; Zhao, Xingzhong

doi:10.1021/acsami.5b06791

Cited by 54 publications

(58 citation statements)

References 53 publications

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“…Another important part of the platform is sLeX-AP; its use significantly improved the capture efficiency of HCC CTCs through this platform. Notablely, our group 19 as well as other groups 23, 37-41 previously applied aptamers as functional molecules to achieve excellent CTCs detection in many types of cancers, which indicated that aptamers were applicable for rare CTCs detection. Especially, epithelial-mesenchymal transition (EMT) have been observed in CTCs, the main characteristic of EMT-CTCs was that the epithelial markers (EpCAM, E-cadherin etc.)…”

Section: Discussionmentioning

confidence: 97%

“…Notably, DNA aptamers were single-stranded oligonucleotides had unique secondary or tertiary structures, and showed highly specific affinity to recognize surface molecules on targeted cells. Aptamers had been used as functional molecules in several kinds of solid tumors and realized efficient and sensitive capture of CTCs 19, 23, 37-41. Furthermore, compared with antibodies, DNA aptamers could be easily and reproducibly synthesized, they had low immunogenicity and high stability.…”

Section: Introductionmentioning

confidence: 99%

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Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepatocellular Circulating Tumor Cells Enrichment

Wang¹,

Zhang²,

Wang³

et al. 2016

Theranostics

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Circulating tumor cells (CTCs) have been considered as the origin of cancer metastasis. Thus, detection of CTCs in peripheral blood is of great value in different types of solid tumors. However, owing to extremely low abundance of CTCs, detection of them has been technically challenging. To establish a simple and efficient method for CTCs detection in patients with hepatocellular carcinoma (HCC), we applied biocompatible and transparent HA/CTS (Hydroxyapatite/chitosan) nanofilm to achieve enhanced topographic interactions with nanoscale cellular surface components, and we used sLex-AP (aptamer for carbohydrate sialyl Lewis X) to coat onto HA/CTS nanofilm for efficient capture of HCC CTCs, these two functional components combined to form our CTC-BioTChip platform. Using this platform, we realized HCC CTCs' capture and identification, the average recovery rate was 61.6% or more at each spiking level. Importantly, our platform identified CTCs (2±2 per 2 mL) in 25 of 42 (59.5%) HCC patients. Moreover, both the positivity rate and the number of detected CTCs were significantly correlated with tumor size, portal vein tumor thrombus, and the TNM (tumor-node-metastasis) stage. In summary, our CTC-BioTChip platform provides a new method allowing for simple but efficient detection of CTCs in HCC patients, and it holds potential of clinically usefulness in monitoring HCC prognosis and guiding individualized treatment in the future.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepatocellular Circulating Tumor Cells Enrichment

Wang¹,

Zhang²,

Wang³

et al. 2016

Theranostics

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“…In recent years, many different CTC-isolation technologies have emerged to improve CTC-enrichment rates from other blood components [109, 165–171]. Based on diverse CTC-features, most approaches relied on 1) physical properties, 2) presence of specific cell markers and 3) combination of both.…”

Section: Boxmentioning

confidence: 99%

“…This third group allows precise control of tiny volumes of fluids under flow through antibody-coated microspots providing a functionalized surface and dynamic flows that exclude nonspecific binding [171]. Although such platforms have increased the sensitivity of CTC-detection and capture, their low flow rates don't allow to process sufficient volume sample for a high CTC-yield.…”

Section: Boxmentioning

confidence: 99%

Stem-like plasticity and heterogeneity of circulating tumor cells: current status and prospect challenges in liver cancer

Correnti

Raggi

2016

Oncotarget

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Poor prognosis and high recurrence remain leading causes of primary liver cancerassociated mortality. The spread of circulating tumor cells (CTCs) in the blood plays a major role in the initiation of metastasis and tumor recurrence after surgery. Nevertheless, only a subset of CTCs can survive, migrate to distant sites and establish secondary tumors. Consistent with cancer stem cell (CSC) hypothesis, stem-like CTCs might represent a potential source for cancer relapse and distant metastasis. Thus, identification of stem-like metastasis-initiating CTC-subset may provide useful clinically prognostic information. This review will emphasize the most relevant findings of CTCs in the context of stem-like biology associated to liver carcinogenesis. In this view, the emerging field of stem-like CTCs may deliver substantial contribution in liver cancer field in order to move to personalized approaches for diagnosis, prognosis and therapy.

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“…The average recovery of HCT116 and MDA cells was shown to be 61% (6) and 96% (5), respectively. Most microdevices demonstrate similar CTC recovery, greater purity, and superior sensitivity compared to technologies like Cellsearch ® (10). Thus, alternate devices have been developed to circumvent the need for centrifugation and reduce the sample processing time, while attempting to maintain or improve sensitivity and specificity.…”

mentioning

confidence: 99%

Microfluidic Immiscible Phase Filtration System for the Isolation of Small Numbers of Cells from Whole Blood

et al. 2019

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Isolation of circulating tumor cells (CTCs) has generated clinical and academic interest due to the important role that CTCs play in cancer metastasis and diagnosis. Here, we present a PDMS and glass prototype of a microfluidic device for the immunomagnetic, immiscible phase filtration based capture, and isolation of MCF-7 breast cancer cells, from various sample matrices including PBS-based buffer, blood plasma, and unprocessed whole blood. Following optimization of surface energy of an oil-water interface, microfluidic geometry, and bead-binding kinematics, our microfluidic device achieved 95 AE 4% recovery of target cells from PBS-based buffer with 95% purity, 90 AE 3% recovery of target cells from blood plasma and recovery of~70 AE 5% from unprocessed whole blood with purity >99% with 1 ml blood samples with 1,000 spiked target cells. From quantitative studies to assess the nonspecific carryover of contaminants from whole blood, we found that our system accomplishes a >175 fold depletion in platelets, >900 fold depletion in erythrocytes, and >1,700 fold depletion in leukocytes with respect to unprocessed whole blood, enabling us to avoid sample pre-processing. In addition, we found that~95% of the isolated target cells were viable, making them suitable for subsequent molecular and cellular studies. We quantify and propose mechanisms for the carryover of platelet, erythrocyte, and leukocyte contamination in purified samples, rather than relying on sample pre-processing. These results validate the continued study of our platform for extraction of CTCs from patient samples and other rare cell isolation applications.

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Capture and Release of Cancer Cells by Combining On-Chip Purification and Off-Chip Enzymatic Treatment

Cited by 54 publications

References 53 publications

Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepatocellular Circulating Tumor Cells Enrichment

Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepatocellular Circulating Tumor Cells Enrichment

Stem-like plasticity and heterogeneity of circulating tumor cells: current status and prospect challenges in liver cancer

Microfluidic Immiscible Phase Filtration System for the Isolation of Small Numbers of Cells from Whole Blood

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