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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 LeeEmail author
Research Paper
  • 53 Downloads

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 (dc), the diameter of cylindrical filter pores (dp), 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 Cae are used to determine the optimized Cae 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 Cae phase diagram is proposed for the first time as a useful tool for design optimization of MEF devices and other microfiltration devices.

Keywords

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

Notes

Acknowledgements

The authors would like to acknowledge the support of a Grant from HKUST-BME Division, the Grants from NSFC (nos. 81372274, 8141101080 and 11702236), Guangzhou Science and Technology Innovation Commission (no. 201704030101), Guangdong Science and Technology Grant (no. 2017B050506001) and Hong Kong ITF Grant (no. GHP/076/17GD).

Supplementary material

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Supplementary material 1 (MP4 6036 kb)
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Supplementary material 2 (DOCX 17149 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Mechanical and Aerospace EngineeringThe Hong Kong University of Science and Technology (HKUST)Hong KongChina
  2. 2.College of Civil Engineering and MechanicsXiangtan UniversityXiangtanChina
  3. 3.Guangzhou First People’s HospitalGuangzhouChina
  4. 4.Sun Yat-sen University Cancer CenterGuangzhouChina
  5. 5.Department of Aerospace and Mechanical EngineeringUniversity of ArizonaTucsonUSA

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