Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cho, Hyeon-Yeol; Choi, Jin‐Ha; Lim, Joungpyo; Lee, Sang-Nam; Choi, Jeong‐Woo

doi:10.3390/cancers13061385

Cited by 23 publications

(18 citation statements)

References 99 publications

(128 reference statements)

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“…In the more widespread case of in vitro CTC capture, microfluidics-based approaches offer an attractive alternative to macroscale techniques, such as bulk magnetic sorting, since they are operator-independent and have the potential to provide precise sorting conditions and continuous sample processing, minimizing rare cell loss. Thus, many efforts have been devoted to the development of microfluidic systems based on magnetism to isolate CTCs in the past decade [110,177,[232][233][234], as recently reviewed by Chen et al [235]. The IsoFlux System (Fluxion Biosciences Inc, South San Francisco, CA) is an example of microfluidics-based technology using IMS and dedicated to CTC isolation brought to the market.…”

Section: Microfluidics-based Approachesmentioning

confidence: 99%

Basic Principles and Recent Advances in Magnetic Cell Separation

Frénéa‐Robin

Marchalot

2022

Magnetochemistry

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Magnetic cell separation has become a key methodology for the isolation of target cell populations from biological suspensions, covering a wide spectrum of applications from diagnosis and therapy in biomedicine to environmental applications or fundamental research in biology. There now exists a great variety of commercially available separation instruments and reagents, which has permitted rapid dissemination of the technology. However, there is still an increasing demand for new tools and protocols which provide improved selectivity, yield and sensitivity of the separation process while reducing cost and providing a faster response. This review aims to introduce basic principles of magnetic cell separation for the neophyte, while giving an overview of recent research in the field, from the development of new cell labeling strategies to the design of integrated microfluidic cell sorters and of point-of-care platforms combining cell selection, capture, and downstream detection. Finally, we focus on clinical, industrial and environmental applications where magnetic cell separation strategies are amongst the most promising techniques to address the challenges of isolating rare cells.

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Section: Microfluidics-based Approachesmentioning

confidence: 99%

Basic Principles and Recent Advances in Magnetic Cell Separation

Frénéa‐Robin

Marchalot

2022

Magnetochemistry

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“…CCSCs express several cancer stem cell markers, such as DCLK1, LGR5, ALDH, CD24, CD166, CD90, CD133 (Figure 3A) and CD44. [32,33,[36][37][38] Kantara et al used multiple CCSCs markers to detect CCSCs in blood, and found that almost all the CCSCs isolated, expressed CK19, [33] suggesting these CCSCs are all epithelial origin. Morphologically, CCSCs have greater cytoskeletal and nucleoskeletal deformability and motility than CTCs, [39] which may be used to distinguish CCSCs from surrounding CTCs.…”

Section: Circulating Cancer Stem Cells (Ccscs): a Small Subpopulation...mentioning

confidence: 99%

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

Huang

Zhou

et al. 2022

Small Methods

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cells (CTCs) are precursors of metastasis in various cancers. They are detached cells slough off the edges of a solid tumor, and then enter the bloodstream or lymphatic system, moving from the primary site to distal organs via the lymphatic channels or the circulation. Although an estimated number of 3.2 × 10 6 tumor cells detach from one gram of tumor tissues per day, [2] CTCs have a relatively short life span that most of them begin to apoptosis within 24 h due to the loss of adhesion to the extracellular matrix, the shear forces of blood flow, or attacks from the immune cells. [3,4] Only a tiny fraction of CTCs that have undergone epithelial-mesenchymal transition (EMT) or CTC clusters formation survive in the bloodstream. [5] After EMT, epithelial CTCs acquire a mesenchymal phenotype, and become invasive and motile. CTCs hold the genetic information of the primary tumor, due to their same origin, thus can act as the surrogate of primary tumor for the monitoring of tumor phenotype/genotype. [6] CTCs counts have been reported correlate to overall survival and/or metastatic relapse, and suggested as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. [7] However, CTCs detection and analysis have two major challenges: their rarity in a typically sampled blood volume (10-50 mL), as well as genetical and phenotypical heterogeneity. [8] Thus, enrichment and detection procedures are the foundation for developing the technologies of CTCs detection. Microfluidic chip is a promising technology for CTCs isolation, identification, and characterization by using their biological and physical properties. It owes unique advantages, such as low-cost, simplicity, reduction in reagent consumption, miniaturization, fast and precise control.The substantial heterogeneity of CTCs determines their variability in expression patterns, [9] which causes difficulties to define a CTC by using specific markers. The most widely used markers to identify CTCs are EpCAM and cytokeratins (CKs). Thus, a long time in the early days, CTCs are defined as EpCAM or CKs positive and CD45 negative. But only epithelial CTCs express these two proteins. CTCs undergoing EMT gradually lose their epithelial features, having no or very low expression of epithelial markers (e.g., EpCAM, CKs, Circulating tumor cells (CTCs) enumeration has been widely used as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. Microfluidic technologies for CTCs enrichment and detection have been developed and commercialized as automation platforms. Currently, in addition to CTCs, some new types of circulating cancer-related cells (e.g., CCSCs, CTECs, CAMLs, and heterotypic CTC clusters) in circulation are also reported to be correlated to cancer diagnosis, metastasis, or prognosis. And they widely differ from the conventional CTCs in positive markers, cellular morphology, or size, which presents a new technological challenge to microfluidic devices that use ...

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“…Today, many papers have reported the integration of microfluidics with electronic sensors. Sensor-integrated microfluidic devices were reported for applications such as DNA hybridization [ 28 , 29 ], polymerase chain reaction (PCR) on-chip [ 30 , 31 ], virus detection [ 32 , 33 ], cancer detection [ 34 , 35 ], circulating tumor cells (CTC) analysis [ 36 , 37 ], exosomes analysis [ 38 , 39 ], nucleic acids analysis [ 40 , 41 ], liquid biopsy-based assays for cancer detection [ 42 ]. CMOS-based sensors integration with microfluidic is put forward for cell analysis [ 43 , 44 ], chemical sensing [ 45 ], optical biosensing [ 46 ], ultraprecise micro pumping [ 47 ], 2D nanomaterial detection [ 48 ], optofluidics biomedical devices [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

A Hybrid Microfluidic Electronic Sensing Platform for Life Science Applications

Panahi

Ghafar-Zadeh

2022

Micromachines

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This paper presents a novel hybrid microfluidic electronic sensing platform, featuring an electronic sensor incorporated with a microfluidic structure for life science applications. This sensor with a large sensing area of 0.7 mm2 is implemented through a foundry process called Open-Gate Junction FET (OG-JFET). The proposed OG-JFET sensor with a back gate enables the charge by directly introducing the biological and chemical samples on the top of the device. This paper puts forward the design and implementation of a PDMS microfluidic structure integrated with an OG-JFET chip to direct the samples toward the sensing site. At the same time, the sensor’s gain is controlled with a back gate electrical voltage. Herein, we demonstrate and discuss the functionality and applicability of the proposed sensing platform using a chemical solution with different pH values. Additionally, we introduce a mathematical model to describe the charge sensitivity of the OG-JFET sensor. Based on the results, the maximum value of transconductance gain of the sensor is ~1 mA/V at Vgs = 0, which is decreased to ~0.42 mA/V at Vgs = 1, all in Vds = 5. Furthermore, the variation of the back-gate voltage from 1.0 V to 0.0 V increases the sensitivity from ~40 mV/pH to ~55 mV/pH. As per the experimental and simulation results and discussions in this paper, the proposed hybrid microfluidic OG-JFET sensor is a reliable and high-precision measurement platform for various life science and industrial applications.

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Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cited by 23 publications

References 99 publications

Basic Principles and Recent Advances in Magnetic Cell Separation

Basic Principles and Recent Advances in Magnetic Cell Separation

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

A Hybrid Microfluidic Electronic Sensing Platform for Life Science Applications

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