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Abstract Circulating tumor cells (CTCs) are shed from primary tumors, circulate in the bloodstream and are capable of initiating metastasis at distant anatomical sites. The detection and molecular characterization of CTCs are pivotal for early-stage cancer diagnosis and prognosis. Recently, microfluidic technology has achieved significant progress in the separation of cells from complex and heterogeneous mixtures for many biomedical applications. Conventional microfluidic platforms exploit the difference in size between the particles to achieve separation, which makes them ineffective for sorting overlapping-sized CTCs. To address this issue, we propose a method using a spiral channel for label-free, and high throughput separation of CTCs coupling Dielectrophoresis (DEP) with inertial microfluidics. A numerical model has been developed to investigate the separation effectiveness of the device over a range of electrical voltage and flow rates. The presented channel is shown to effectively isolate similar-sized CTCs from the white blood cells (WBCs) in a single-stage separation process. Subsequently, optimum working parameters to enhance separation efficiency have been proposed. The hybrid microfluidic device can provide valuable insight into the development of a robust, inexpensive, and efficient platform for cell separation with reduced analysis time for future cancer research and treatment.
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Continuous CTC separation through a DEP ‐based contraction–expansion inertial microfluidic channel
Abstract 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 V p–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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- Award ID(s):
- 1917299
- PAR ID:
- 10448868
- Date Published:
- Journal Name:
- Biotechnology Progress
- Volume:
- 39
- Issue:
- 4
- ISSN:
- 8756-7938
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/btpr.3341
