Microfluidic devices to enrich and isolate circulating tumor cells

Myung, Ja Hye; Hong, Seungpyo

doi:10.1039/c5lc00947b

Cited by 94 publications

(49 citation statements)

References 81 publications

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“…Isolation of CTCs from blood is critical owing to the fact that metastatic CTCs may hold different genomic and phenotypic properties which may provide insights for prognosis and effective treatment. Focusing biological particles and cells using microfluidic systems have been implemented as an efficient CTCs enumeration and enrichment method for clinical diagnostics applications89. Focusing particles and cells into a narrow stream is a requirement for these emerging applications and for understanding the underlying physics of particle/cell focusing in microfluidics10.…”

mentioning

confidence: 99%

Inertial Focusing of Microparticles in Curvilinear Microchannels

Özbey

Karimzadehkhouei

Akgönül

et al. 2016

Sci Rep

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A passive, continuous and size-dependent focusing technique enabled by “inertial microfluidics”, which takes advantage of hydrodynamic forces, is implemented in this study to focus microparticles. The objective is to analyse the decoupling effects of inertial forces and Dean drag forces on microparticles of different sizes in curvilinear microchannels with inner radius of 800 μm and curvature angle of 280°, which have not been considered in the literature related to inertial microfluidics. This fundamental approach gives insight into the underlying physics of particle dynamics and offers continuous, high-throughput, label-free and parallelizable size-based particle separation. Our design allows the same footprint to be occupied as straight channels, which makes parallelization possible with optical detection integration. This feature is also useful for ultrahigh-throughput applications such as flow cytometers with the advantages of reduced cost and size. The focusing behaviour of 20, 15 and 10 μm fluorescent polystyrene microparticles was examined for different channel Reynolds numbers. Lateral and vertical particle migrations and the equilibrium positions of these particles were investigated in detail, which may lead to the design of novel microfluidic devices with high efficiency and high throughput for particle separation, rapid detection and diagnosis of circulating tumour cells with reduced cost.

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mentioning

confidence: 99%

Inertial Focusing of Microparticles in Curvilinear Microchannels

Özbey

Karimzadehkhouei

Akgönül

et al. 2016

Sci Rep

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“…Still the CellSearch system remains the gold standard for CTC enumeration and has set the bar quite high (Bidard et al, 2014;Mehra et al, 2015). Over the years several alternative technologies have been developed reviewed extensively elsewhere (Alix-Panabi eres and Pantel, 2014; Barradas and Terstappen, 2013;Krebs et al, 2014;Myung and Hong, 2015) and demonstrated to detect CTC both by targeting EpCAM and not targeting EpCAM but using Figure 6 e What is and what isn't a CTC. Left part of the figure shows seven areas with objects in which the CellTracks software identified cytokeratin (CK) as well as DNA staining.…”

Section: Discussionmentioning

confidence: 99%

Challenges in circulating tumor cell detection by the CellSearch system

2015

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Enumeration and characterization of circulating tumor cells (CTC) hold the promise of a real time liquid biopsy. They are however present in a large background of hematopoietic cells making their isolation technically challenging. In 2004, the CellSearch system was introduced as the first and only FDA cleared method designed for the enumeration of circulating tumor cells in 7.5 mL of blood. Presence of CTC detected by CellSearch is associated with poor prognosis in metastatic carcinomas. CTC remaining in patients after the first cycles of therapy indicates a futile therapy. Here we review challenges faced during the development of the CellSearch system and the difficulties in assigning objects as CTC. The large heterogeneity of CTC and the different approaches introduced in recent years to isolate, enumerate and characterize CTC results in a large variation of the number of CTC reported urging the need for uniform definitions and at least a clear definition of what the criteria are for assigning an object as a CTC.

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“…Most research has been conducted on devices fabricated using the classical soft lithography process for fast prototyping. This process, however, has some drawbacks regarding reproducibility and scalability . Manual alignment of a cast polydimethylsiloxane (PDMS) channel structure to electrodes defined on a glass substrate typically requires a high level of manual skill .…”

Section: Critical Challenges In Dep Enrichment Of Ctcsmentioning

confidence: 99%

“…Manual alignment of a cast polydimethylsiloxane (PDMS) channel structure to electrodes defined on a glass substrate typically requires a high level of manual skill . Non‐specific binding of cells to the PDMS structure is another possible impediment to the yield and the general functionality of a device . On the other hand, glass‐ and silicon‐based fabrication techniques have the advantages of robustness and scalability, although the fabrication process requires advanced knowledge and skills, and specialized cleanroom equipment.…”

Section: Critical Challenges In Dep Enrichment Of Ctcsmentioning

confidence: 99%

Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells

et al. 2019

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Circulating tumor cells (CTCs) play an essential role in the metastasis of tumors, and thus can serve as a valuable prognostic factor for malignant diseases. As a result, the ability to isolate and characterize CTCs is essential. This review underlines the potential of dielectrophoresis for CTCs enrichment. It begins by summarizing the key performance parameters and challenges of CTCs isolation using microfluidics. The two main categories of CTCs enrichment—affinity‐based and label‐free methods—are analysed, emphasising the advantages and disadvantages of each as well as their clinical potential. While the main argument in favour of affinity‐based methods is the strong specificity of CTCs isolation, the major advantage of the label‐free technologies is in preserving the integrity of the cellular membrane, an essential requirement for downstream characterization. Moving forward, we try to answer the main question: “What makes dielectrophoresis a method of choice in CTCs isolation?” The uniqueness of dielectrophoretic CTCs enrichment resides in coupling the specificity of the isolation process with the conservation of the membrane surface. The specificity of the dielectrophoretic method stems from the differences in the dielectric properties between CTCs and other cells in the blood: the capacitances of the malignantly transformed cellular membranes of CTCs differ from those of other cells. Examples of dielectrophoretic devices are described and their performance evaluated. Critical requirements for using dielectrophoresis to isolate CTCs are highlighted. Finally, we consider that DEP has the potential of becoming a cytometric method for large‐scale sorting and characterization of cells.

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Microfluidic devices to enrich and isolate circulating tumor cells

Cited by 94 publications

References 81 publications

Inertial Focusing of Microparticles in Curvilinear Microchannels

Inertial Focusing of Microparticles in Curvilinear Microchannels

Challenges in circulating tumor cell detection by the CellSearch system

Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells

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