Computational Analysis of Enhanced Circulating Tumour Cell (CTC) Separation in a Microfluidic System with an Integrated Dielectrophoretic-Magnetophorectic (DEP-MAP) Technique

Abstract

Abstract:Cell based cancer analysis is an important analytic method to monitor cancer progress on stages by detecting the density of circulating tumour cells (CTCs) in the blood. Among the existing microfluidic techniques, dielectrophoresis (DEP), which is a label-free detection method, is favoured by researchers. However, because of the high conductivity of blood as well as the rare presence of CTCs, high separation efficiency is difficult to achieve in most DEP microdevices. Through this study, we have proposed a strategy to improve the isolation performance, as such by integrating a magnetophoretic (MAP) platform into a DEP device. Several important aspects to be taken into MAP design consideration, such as permanent magnet orientation, magnetic track configuration, fluid flow parameter and separation efficiency, are discussed. The design was examined and validated by numerical simulation using COMSOL Multiphysics v4.4 software (COMSOL Inc., Burlington, MA, USA), mainly presented in three forms: surface plot, line plot, and arrow plot. From these results, we showed that the use of a single permanent magnet coupled with an inbuilt magnetic track of 250 µm significantly strengthens the magnetic field distribution within the proposed MAP stage. Besides, in order to improve dynamic pressure without compromising the uniformity of fluid flow, a wide channel inlet and a tree-like network were employed. When the cell trajectory within a finalized MAP stage is computed with a particle tracing module, a high separation efficiency of red blood cell (RBC) is obtained for blood samples corresponding up to a dilution ratio of 1:7. Moreover, a substantial enhancement of the CTCs' recovery rate was also observed in the simulation when the purposed platform was integrated with a planar DEP microdevice.

Smart Material‐Integrated Systems for Isolation and Profiling of Rare Cancer Cells and Emboli

“…This technology requires three main actions, such as sampling, processing, and validation. The capability of isolating rare cells comes from different passive methods that tailor the microfilters of varying pore sizes, [ 107 ] flow chamber geometries, [ 108 ] microstructures, [ 109 ] and flow density [ 110 ] with precision and active methods, which rely on compressibility, [ 111 ] polarizability, [ 112 ] and magnetic susceptibility as shown in Table 1 . [ 113 ] For the CTCs/CTM enumeration and further analysis for downstream processes, the surface chemistry of microfluidic platforms needs to be designed to control the capture and release of tumor cells.…”

Enhanced microfluidic multi-target separation by positive and negative magnetophoresis

“…The 0.05 × EMG 408 (Ferrotec, USA) is adopted as the ferrofluid medium because of its reasonable biocompatibility and optical properties 36 . All properties of the materials used in simulations are summarized in Table 1 27 , 68 – 73 .…”

“…Hybridization between the dielectrophoretic DEP and the magnetophoretic (MAP) separation methods could also improve performance. Low and Kadri 27 developed a computational model to study the integration of a magnetophoretic platform with a DEP-based system to separate circulating tumor cells. Shamloo et al 28 conducted a numerical study of a two-step micro separator device that uses MAP physics to separate red blood cells (RBCs) and platelets (PLTs) in the first step, followed by the DEP technique to separate white blood cells (WBCs) and circulating tumor cells (CTCs) in the second step.…”

Progress of Microfluidic Continuous Separation Techniques for Micro-/Nanoscale Bioparticles

“…Since biological subjects, such as cells, have dielectric constants, the DEP can be used to manipulate, transport, separate, and sort different types of bioparticles, which is based on differentiation of dielectric and conducting properties of the particles [ 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 ]. For example, Figure 5 B(i) shows a general scheme for an AC-DEP microfluidic device for continuous cell characterization and separation.…”