Design and Simulation of an Integrated Centrifugal Microfluidic Device for CTCs Separation and Cell Lysis

Abstract

Separation of circulating tumor cells (CTCs) from blood samples and subsequent DNA extraction from these cells play a crucial role in cancer research and drug discovery. Microfluidics is a versatile technology that has been applied to create niche solutions to biomedical applications, such as cell separation and mixing, droplet generation, bioprinting, and organs on a chip. Centrifugal microfluidic biochips created on compact disks show great potential in processing biological samples for point of care diagnostics. This study investigates the design and numerical simulation of an integrated microfluidic device, including a cell separation unit for isolating CTCs from a blood sample and a micromixer unit for cell lysis on a rotating disk platform. For this purpose, an inertial microfluidic device was designed for the separation of target cells by using contraction–expansion microchannel arrays. Additionally, a micromixer was incorporated to mix separated target cells with the cell lysis chemical reagent to dissolve their membranes to facilitate further assays. Our numerical simulation approach was validated for both cell separation and micromixer units and corroborates existing experimental results. In the first compartment of the proposed device (cell separation unit), several simulations were performed at different angular velocities from 500 rpm to 3000 rpm to find the optimum angular velocity for maximum separation efficiency. By using the proposed inertial separation approach, CTCs, were successfully separated from white blood cells (WBCs) with high efficiency (~90%) at an angular velocity of 2000 rpm. Furthermore, a serpentine channel with rectangular obstacles was designed to achieve a highly efficient micromixer unit with high mixing quality (~98%) for isolated CTCs lysis at 2000 rpm.

Design of a Hybrid Inertial and Magnetophoretic Microfluidic Device for CTCs Separation from Blood

“…Circulating tumor cells (CTCs) captured from blood samples have great potential for the diagnosis and treatment of cancer. Microfluidics has emerged as a great technology for cell separation application by exploiting different properties of cells and different physical principles [ 1 , 2 ]. These techniques are categorized as microfluidic microfilters, deterministic lateral displacement, hydrodynamic filtration, inertial methods as well as methods based on external force fields such as dielectrophoretic (DEP), acoustic, magnetic, and optical separation methods [ 3 , 4 ].…”

Innovative 3D Microfluidic Tools for On-Chip Fluids and Particles Manipulation: From Design to Experimental Validation

“…A particularly crucial element to shift standard assays to on-chip reactions are micromixers which have a wide range of bio-applications such as studies on living cells for medical diagnostics, nanoparticles synthesis for chemistry, and biotechnologies analysis like polymerase chain reaction (PCR) [ 24 , 25 , 26 ]. In this respect, many research groups have focused their attention on this aim.…”

Sheath‐assisted versus sheathless dielectrophoretic particle separation

“…These separation methods are generally categorized into passive and active methods [2,3]. Microfiltration [4], inertia‐based [5], pinched flow fractionation [6], and deterministic lateral displacement [7] are among the passive methods. Dielectrophoretic [8], acoustophoretic [9], magnetic [10], and optic forces [11] are the most popular active methods used for sorting and separation.…”