A nonlinear two-degree-of-freedom mass–damper–spring model to predict the isolation of circulating tumor cells in microfluidic-elasto-filtration devices

Huahuang Luo, Cong Zhao, Kui Song, Dayu Liu, Wenjuan Ma, Xingsu Yu, Huifang Su, Zhenfeng Zhang, Yitshak Zohar, Yi Kuen Lee

Research output: Contribution to journalArticle

Abstract

Circulating tumor cell (CTC) isolation has made positive impacts on metastatic detection and therapy analysis for cancer patients. Microfluidic-elasto-filtration (MEF) device based on the critical elasto-capillary number (Ca e * ) has been proposed to utilize the optimal multi-parameter conditions, including cell diameter (d c ), the diameter of cylindrical filter pores (d p ), nonlinear cell elasticity and hydrodynamic drag force, for selectively capturing CTCs and depleting white blood cells (WBCs). In this paper, we propose a novel two-degree-of-freedom nonlinear mass–damper–spring (m–c–k) model to predict the dynamic behaviors of CTCs and WBCs in a generic MEF device. This model enables the optimization of the device design to achieve extremely high CTC capture efficiency and WBC depletion efficiency. In particular, the function of nonlinear cell stiffness specific to different cell types and MEF’s pore diameters is first determined by finite element method with neo-Hookean hyperelastic model, based on which the mechanical behaviors of CTCs and WBCs in MEF devices are systematically studied. Herein, the predicted normalized deformations of a CTC and WBC as a function of Ca e are used to determine the optimized Ca e of 0.043, consistent with the experimental results from the fabricated MEF devices using MCF-7 cells (0.04 ± 0.006). In addition, the normalized cell diameter versus Ca e phase diagram is proposed for the first time as a useful tool for design optimization of MEF devices and other microfiltration devices.

Original languageEnglish (US)
Article number72
JournalMicrofluidics and Nanofluidics
Volume23
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Microfluidics
leukocytes
Tumors
isolation
Blood
tumors
degrees of freedom
Cells
cells
Microfiltration
porosity
Phase diagrams
Drag
Elasticity
design optimization
Hydrodynamics
Stiffness
Finite element method
drag
therapy

Keywords

  • Capture efficiency
  • Circulating tumor cells
  • Elasto-capillary number
  • Mass–damper–spring model
  • Microfluidic-elasto-filtration
  • WBC depletion

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Materials Chemistry

Cite this

A nonlinear two-degree-of-freedom mass–damper–spring model to predict the isolation of circulating tumor cells in microfluidic-elasto-filtration devices. / Luo, Huahuang; Zhao, Cong; Song, Kui; Liu, Dayu; Ma, Wenjuan; Yu, Xingsu; Su, Huifang; Zhang, Zhenfeng; Zohar, Yitshak; Lee, Yi Kuen.

In: Microfluidics and Nanofluidics, Vol. 23, No. 5, 72, 01.05.2019.

Research output: Contribution to journalArticle

Luo, Huahuang ; Zhao, Cong ; Song, Kui ; Liu, Dayu ; Ma, Wenjuan ; Yu, Xingsu ; Su, Huifang ; Zhang, Zhenfeng ; Zohar, Yitshak ; Lee, Yi Kuen. / A nonlinear two-degree-of-freedom mass–damper–spring model to predict the isolation of circulating tumor cells in microfluidic-elasto-filtration devices. In: Microfluidics and Nanofluidics. 2019 ; Vol. 23, No. 5.
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abstract = "Circulating tumor cell (CTC) isolation has made positive impacts on metastatic detection and therapy analysis for cancer patients. Microfluidic-elasto-filtration (MEF) device based on the critical elasto-capillary number (Ca e * ) has been proposed to utilize the optimal multi-parameter conditions, including cell diameter (d c ), the diameter of cylindrical filter pores (d p ), nonlinear cell elasticity and hydrodynamic drag force, for selectively capturing CTCs and depleting white blood cells (WBCs). In this paper, we propose a novel two-degree-of-freedom nonlinear mass–damper–spring (m–c–k) model to predict the dynamic behaviors of CTCs and WBCs in a generic MEF device. This model enables the optimization of the device design to achieve extremely high CTC capture efficiency and WBC depletion efficiency. In particular, the function of nonlinear cell stiffness specific to different cell types and MEF’s pore diameters is first determined by finite element method with neo-Hookean hyperelastic model, based on which the mechanical behaviors of CTCs and WBCs in MEF devices are systematically studied. Herein, the predicted normalized deformations of a CTC and WBC as a function of Ca e are used to determine the optimized Ca e of 0.043, consistent with the experimental results from the fabricated MEF devices using MCF-7 cells (0.04 ± 0.006). In addition, the normalized cell diameter versus Ca e phase diagram is proposed for the first time as a useful tool for design optimization of MEF devices and other microfiltration devices.",
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AU - Zhao, Cong

AU - Song, Kui

AU - Liu, Dayu

AU - Ma, Wenjuan

AU - Yu, Xingsu

AU - Su, Huifang

AU - Zhang, Zhenfeng

AU - Zohar, Yitshak

AU - Lee, Yi Kuen

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AB - Circulating tumor cell (CTC) isolation has made positive impacts on metastatic detection and therapy analysis for cancer patients. Microfluidic-elasto-filtration (MEF) device based on the critical elasto-capillary number (Ca e * ) has been proposed to utilize the optimal multi-parameter conditions, including cell diameter (d c ), the diameter of cylindrical filter pores (d p ), nonlinear cell elasticity and hydrodynamic drag force, for selectively capturing CTCs and depleting white blood cells (WBCs). In this paper, we propose a novel two-degree-of-freedom nonlinear mass–damper–spring (m–c–k) model to predict the dynamic behaviors of CTCs and WBCs in a generic MEF device. This model enables the optimization of the device design to achieve extremely high CTC capture efficiency and WBC depletion efficiency. In particular, the function of nonlinear cell stiffness specific to different cell types and MEF’s pore diameters is first determined by finite element method with neo-Hookean hyperelastic model, based on which the mechanical behaviors of CTCs and WBCs in MEF devices are systematically studied. Herein, the predicted normalized deformations of a CTC and WBC as a function of Ca e are used to determine the optimized Ca e of 0.043, consistent with the experimental results from the fabricated MEF devices using MCF-7 cells (0.04 ± 0.006). In addition, the normalized cell diameter versus Ca e phase diagram is proposed for the first time as a useful tool for design optimization of MEF devices and other microfiltration devices.

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