Continual collection and re-separation of circulating tumor cells from blood using multi-stage multi-orifice flow fractionation

Moon, Heui Soo; Kwon, Kee Woong; Hyun, Kyung A.; Sim, Tae Seok; Park, Jae Chan; Lee, Jeong Gun; Jung, Hyo Il

doi:10.1063/1.4788914

Cited by 67 publications

(61 citation statements)

References 30 publications

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“…Recently, there have been many attempts to develop a reliable, rapid and sensitive method for the isolation and detection of CTCs, including immunomagnetic separation, 2,3 affinity chromatography separation, 4,5 and label-free separation. [6][7][8][9][10][11][12] Despite the detection and analysis of CTCs offer a promising non-invasive diagnostic approach for the diagnosis and prognosis of cancer, its use in clinical practice remains limited because of the rarity of CTCs in blood, the difficulty of isolating CTCs and the complexity of CTCs identification and enumeration. In contrast to the isolation and detection of CTCs, the protein-based biomarker tests are easier and more convenient which do not need labor-intensive cell capture and identification and has the potential to allow rapid point-of-care use.…”

Section: Introductionmentioning

confidence: 99%

Direct detection of cancer biomarkers in blood using a “place n play” modular polydimethylsiloxane pump

Zhang

Liao

et al. 2013

Biomicrofluidics

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Cancer biomarkers have significant potential as reliable tools for the early detection of the disease and for monitoring its recurrence. However, most current methods for biomarker detection have technical difficulties (such as sample preparation and specific detector requirements) which limit their application in point of care diagnostics. We developed an extremely simple, power-free microfluidic system for direct detection of cancer biomarkers in microliter volumes of whole blood. CEA and CYFRA21-1 were chosen as model cancer biomarkers. The system automatically extracted blood plasma from less than 3 ll of whole blood and performed a multiplex sample-to-answer assay (nano-ELISA (enzyme-linked immunosorbent assay) technique) without the use of external power or extra components. By taking advantage of the nano-ELISA technique, this microfluidic system detected CEA at a concentration of 50 pg/ml and CYFRA21-1 at a concentration of 60 pg/ml within 60 min. The combination of PnP polydimethylsiloxane (PDMS) pump and nano-ELISA technique in a single microchip system shows great promise for the detection of cancer biomarkers in a drop of blood. V C 2013 AIP Publishing LLC. [http://dx

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Section: Introductionmentioning

confidence: 99%

Direct detection of cancer biomarkers in blood using a “place n play” modular polydimethylsiloxane pump

Zhang

Liao

et al. 2013

Biomicrofluidics

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“…[4][5][6][7] In a microfluidic system, flow features, which in a large part determine the manipulation functions of the system, [8][9][10][11] can be obtained by regulating the structure of the microchannels. The microvortex, a special fluid effect generated in sudden expansion or curved microchannels, is of great importance for particle manipulation.…”

Section: Introductionmentioning

confidence: 99%

Lattice Boltzmann numerical simulation and experimental research of dynamic flow in an expansion-contraction microchannel

et al. 2013

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This paper applies the lattice Boltzmann method (LBM) to a 3D simulation of micro flows in an expansion-contraction microchannel. We investigate the flow field under various inlet flow rates and cavity structures, and then systematically study the flow features of the vortex and Dean flow in this channel. Vortex formation analysis demonstrates that there is no observable vortex generated when the inlet flow rate is low enough. As the inlet flow rate increases, a small vortex first appears near the inlet, and then this vortex region will keep expanding until it fully occupies the cavity. A smaller cavity width may result in a larger vortex but the vortex is less influenced by cavity length. The Dean flow features at the outlet become more apparent with increasing inlet flow rate and more recirculation regions can be observed in the cross-section under over high inlet flow rate. In order to support the simulation results, some experimental processes are conducted successfully. It validates that the applied model can accurately characterize the flow in the microchannel. Results of simulations and experiments in this paper provide insights into the design and operation of microfluidic systems for particle/cell manipulation.

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“…11,12 For example, the experiments of sorting, separation, and trapping of CTCs have been performed using microfluidic systems with similar hydrodynamically engineered configurations. [13][14][15] To optimize the functionalities of these systems, one needs to understand the hydrodynamic behavior of the particles so as to manipulate them in a controlled manner. Karimi et al briefly reviewed the hydrodynamic mechanisms of cell and particle trapping.…”

Section: Introductionmentioning

confidence: 99%

Finite element simulations of hydrodynamic trapping in microfluidic particle-trap array systems

Nehorai

2013

Biomicrofluidics

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Computational fluid dynamic (CFD) simulation is a powerful tool in the design and implementation of microfluidic systems, especially for systems that involve hydrodynamic behavior of objects such as functionalized microspheres, biological cells, or biopolymers in complex structures. In this work, we investigate hydrodynamic trapping of microspheres in a novel microfluidic particle-trap array device by finite element simulations. The accuracy of the time-dependent simulation of a microsphere's motion towards the traps is validated by our experimental results. Based on the simulation, we study the fluid velocity field, pressure field, and force and stress on the microsphere in the device. We further explore the trap array's geometric parameters and critical fluid velocity, which affect the microsphere's hydrodynamic trapping. The information is valuable for designing microfluidic devices and guiding experimental operation. Besides, we provide guidelines on the simulation set-up and release an openly available implementation of our simulation in one of the popular FEM softwares, COMSOL Multiphysics. Researchers may tailor the model to simulate similar microfluidic systems that may accommodate a variety of structured particles. Therefore, the simulation will be of particular interest to biomedical research involving cell or bead transport and migration, blood flow within microvessels, and drug delivery.

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Continual collection and re-separation of circulating tumor cells from blood using multi-stage multi-orifice flow fractionation

Cited by 67 publications

References 30 publications

Direct detection of cancer biomarkers in blood using a “place n play” modular polydimethylsiloxane pump

Direct detection of cancer biomarkers in blood using a “place n play” modular polydimethylsiloxane pump

Lattice Boltzmann numerical simulation and experimental research of dynamic flow in an expansion-contraction microchannel

Finite element simulations of hydrodynamic trapping in microfluidic particle-trap array systems

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