Circulating tumor cells (CTCs) have been proven to have significant prognostic, diagnostic, and clinical values in early-stage cancer detection and treatment. The efficient separation of CTCs from peripheral blood can ensure intact and viable CTCs and can, thus, give proper genetic characterization and drug innovation. In this study, continuous and high-throughput separation of MDA-231 CTCs from overlapping sized white blood cells (WBCs) is achieved by modifying inertial cell focusing with dielectrophoresis (DEP) in a single-stage microfluidic platform by numeric simulation. The DEP is enabled by embedding interdigitated electrodes with alternating field control on a serpentine microchannel to avoid creating two-stage separation. Rather than using the electrokinetic migration of cells which slows down the throughput, the system leverages the inertial microfluidic flow to achieve high-speed continuous separation. The cell migration and cell positioning characteristics are quantified through coupled physics analyses to evaluate the effects of the applied voltages and Reynolds numbers (Re) on the separation performance. The results indicate that the introduction of DEP successfully migrates WBCs away from CTCs and that separation of MDA-231 CTCs from similar sized WBCs at a high Re of 100 can be achieved with a low voltage of magnitude 4 ×10 6 V/m. Additionally, the viability of MDA-231 CTCs is expected to be sustained after separation due to the short-term DEP exposure. The developed technique could be exploited to design active microchips for high-throughput separation of mixed cell beads despite their significant size overlap, using DEP-modified inertial focusing controlled simply by adjusting the applied external field.
A simple, low‐cost, three‐dimensional (3D) lab‐on‐a‐foil microfluidic device for dielectrophoretic separation of circulating tumor cells (CTCs) is designed and constructed. Disposable thin films are cut by xurography and microelectrode array are made with rapid inkjet printing. The multilayer device design allows the studying of spatial movements of CTCs and red blood cells (RBCs) under dielectrophoresis (DEP). A numerical simulation was performed to find the optimum driving frequency of RBCs and the crossover frequency for CTCs. At the optimum frequency, RBCs were lifted 120 µm in z‐axis direction by DEP force, and CTCs were not affected due to negligible DEP force. By utilizing the displacement difference, the separation of CTCs (modeled with A549 lung carcinoma cells) from RBCs in z‐axis direction was achieved. With the nonuniform electric field at optimized driving frequency, the RBCs were trapped in the cavities above the microchannel, whereas the A549 cells were separated with a high capture rate of 86.3% ± 0.2%. The device opens not only the possibility for 3D high‐throughput cell separation but also for future developments in 3D cell manipulation through rapid and low‐cost fabrication.
The efficient isolation of viable and intact circulating tumor cells (CTCs) from blood is critical for the genetic analysis of cancer cells, prediction of cancer progression, development of drugs, and evaluation of therapeutic treatments. While conventional cell separation devices utilize the size difference between CTCs and other blood cells, they fail to separate CTCs from white blood cells (WBCs) due to significant size overlap. To overcome this issue, we present a novel approach that combines curved contraction–expansion (CE) channels with dielectrophoresis (DEP) and inertial microfluidics to isolate CTCs from WBCs regardless of size overlap. This label‐free and continuous separation method utilizes dielectric properties and size variation of cells for the separation of CTCs from WBCs. The results demonstrate that the proposed hybrid microfluidic channel can effectively isolate A549 CTCs from WBCs regardless of their size with a throughput of 300 μL/min, achieving a high separation distance of 233.4 μm at an applied voltage of 50 Vp–p. The proposed method allows for the modification of cell migration characteristics by controlling the number of CE sections of the channel, applied voltage, applied frequency, and flow rate. With its unique features of a single‐stage separation, simple design, and tunability, the proposed method provides a promising alternative to the existing label‐free cell separation techniques and may have a wide range of applications in biomedicine.
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