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

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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.

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Abbreviations

C s :

Thermophoretic correction factor

d p :

Diameter of particle/m

F B :

Buoyancy force/N

F D :

Drag force/N

F g :

Gravity force/N

F T :

Thermophoretic force/N

g :

Gravitational acceleration/m s−2

k :

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

Kn :

Knudsen number

k P :

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

m p :

Mass of particle/kg

p :

Pressure/Pa

r p :

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

λ :

Molecular mean free path

μ :

Dynamic viscosity/Pa s

ρ :

Density of blood/g mL−1

ρ p :

Density of particle/g mL−1

τ p :

Defined in Eq. (5)

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

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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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Authors and Affiliations

  1. Sensors and Integrated Bio-Microfluidics/MEMS laboratory, School of Mechanical Engineering, Iran University of Science and Technology, Narmak, Tehran, 16846-13114, Iran

    Sasan Asiaei, Vahid Darvishi, Mohammad Hossein Davari, Delaram Zohrevandi & Hesam Moghadasi

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  1. Sasan Asiaei
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  2. Vahid Darvishi
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Correspondence to Sasan Asiaei.

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Asiaei, S., Darvishi, V., Davari, M.H. et al. Thermophoretic isolation of circulating tumor cells, numerical simulation and design of a microfluidic chip. J Therm Anal Calorim 137, 831–839 (2019). https://doi.org/10.1007/s10973-018-07996-7

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  • DOI: https://doi.org/10.1007/s10973-018-07996-7

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