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Thermophoretic isolation of circulating tumor cells, numerical simulation and design of a microfluidic chip

  • Sasan AsiaeiEmail author
  • Vahid Darvishi
  • Mohammad Hossein Davari
  • Delaram Zohrevandi
  • Hesam Moghadasi
Article
  • 37 Downloads

Abstract

In this work, we design a novel microfluidic chip to analyze and simulate the thermophoretic isolation of circulating tumor cells. For the first time, separation of circulating tumor cells from same size peripheral blood cells is examined by thermophoresis. Moreover, a discrete heat source was used to attenuate the separation efficiency, instead of a continuous heat source. Physical properties, such as thermal conductivity, gravity and hydrodynamic forces, were used in numerical design of a microfluidic chip to preferably move white blood cells toward colder walls, due to thermophoresis. To examine the separation process, or differentiated upward migration of cells between the fluid layers, the creeping flow and continuity equations are simultaneously solved along with the constituent forces by FEM modeling. Results show that upon applying a minimum temperature difference of 1 °C, white blood cells are effectively separated from tumor cells, in a 4.5-mm-long microchannel. Maintaining an oscillating/symmetrical temperature gradient in the longitudinal direction minimizes the required separation length of the channel. Moreover, for samples with relatively wide range of size distributions, thermophoresis can robustly separate the analytes, even for the same diameter analytes where the difference in buoyancy or gravity forces is infinitesimal or not present. Such small temperature difference in walls does not denature cells, the overall design is relatively cheap to apply and requires simple fabrication, and the separation is implemented label-free.

Keywords

Thermophoresis Circulating tumor cell Microfluidics Separation Discrete heat sources 

List of symbols

Cs

Thermophoretic correction factor

dp

Diameter of particle/m

FB

Buoyancy force/N

FD

Drag force/N

Fg

Gravity force/N

FT

Thermophoretic force/N

g

Gravitational acceleration/m s−2

k

Thermal conductivity of blood/W m−1 K−1

Kn

Knudsen number

kP

Thermal conductivity of particle/W m−1 K−1

mp

Mass of particle/kg

p

Pressure/Pa

rp

Radius of particle/m

Re

Reynolds number

u

Carrier fluid velocity/m s−1

\(\vec{u}\)

Velocity vector/m s−1

T

Temperature/K

t

Time/s

\(\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\rightharpoonup}$}} {V}_{\text{p}}\)

Particle velocity vector/m s−1

Greek symbols

λ

Molecular mean free path

μ

Dynamic viscosity/Pa s

ρ

Density of blood/g mL−1

ρp

Density of particle/g mL−1

τp

Defined in Eq. (5)

Abbreviations

CTC

Circulating tumor cell

BDF

Backward differentiation formula

FEM

Finite element method

MUMPS

Multifrontal massively parallel sparse direct solver

RBC

Red blood cell

WBC

White blood cell

Notes

Acknowledgements

This research was financially supported by the Ministry of Science, Research and Technology (MSRT), Iran. The authors would like to acknowledge the products and services provided by MSRT that facilitated this research, including the CAD software.

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Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  1. 1.Sensors and Integrated Bio-Microfluidics/MEMS laboratory, School of Mechanical EngineeringIran University of Science and TechnologyNarmak, TehranIran

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