Reliable separation of circulating tumor cells from blood cells is crucial for early cancer diagnosis and prognosis. Many conventional microfluidic platforms take advantage of the size difference between particles for their separation, which renders them impractical for sorting overlapping‐sized cells. To address this concern, a hybrid inertial‐dielectrophoretic microfluidic chip is proposed in this work for continuous and single‐stage separation of lung cancer cell line A549 cells from white blood cells of overlapping size. The working mechanism of the proposed spiral microchannel embedded with planar interdigitated electrodes is validated against the experimental results. A numerical investigation is carried out over a range of flow conditions and electric field intensity to determine the separation efficiency and migration characteristics of the cell mixture. The results demonstrate the unique capability of the proposed microchannel to achieve high‐throughput separation of cells at low applied voltages in both vertical and lateral directions. A significant lateral separation distance between the CTCs and the WBCs has been achieved, which allows for high‐resolution and effective separation of cells. The separation resolution can be controlled by adjusting the strength of the applied electric field. Furthermore, the results demonstrate that the lateral separation distance is maximum at a voltage termed the critical voltage, which increases with the increase in the flow rate. The proposed microchannel and the developed technique can provide valuable insight into the development of a tunable and robust medical device for effective and high‐throughput separation of cancer cells from the WBCs.
Embedded pillar microstructures are an efficient approach for controlling and sculpting shear flow in a microchannel but have not yet demonstrated to be effective for deformability‐based cell separation and sorting. Although simple pillar configurations (lattice, line sequence) work well for size‐based separation of rigid particles, these have a low separation efficiency for circulating cells. The objective of this study is to optimize sequenced microstructures for separation of deformable cells. This is achieved by numerical analysis of pairwise cell migration in a microchannel with multiple pillars, where size, longitudinal spacing, and lateral location as well as the cell elasticity and size vary. This study reveals two basic pillar configurations optimized for deformability‐based separation: “duplet” that consists of two closely spaced pillars positioned far below the centerline and above the centerline halfway to the wall; and “triplet” composed of three widely spaced pillars located below, above and at the centerline, respectively. The duplet configuration is well suited for deformable cell separation in short channels, whereas the triplet or a combination of duplets and triplets provides even better separation in long channels. These optimized pillar microstructures can dramatically improve microfluidic methods for sorting and isolation of blood and rare circulating tumor cells.
more » « less- PAR ID:
- 10449341
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Theory and Simulations
- Volume:
- 4
- Issue:
- 9
- ISSN:
- 2513-0390
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Isolation and detection of circulating tumor cells (CTCs) hold significant importance for the early diagnosis of cancer and the assessment of therapeutic strategies. However, the scarcity of CTCs among peripheral blood cells presents a major challenge to their detection. Additionally, a similar size range between CTCs and white blood cells (WBCs) makes conventional microfluidic platforms inadequate for the isolation of CTCs. To overcome these challenges, in this study, a novel inertial‐dielectrophoretic microfluidic channel for size‐independent, single‐stage separation of CTCs from WBCs has been presented. The proposed device utilizes a spiral microchannel embedded with interdigitated electrodes. A numerical model is developed and validated to investigate the influence of various parameters related to the channel design, fluid flow, and electrode configuration. It was found that optimal separation of CTCs could be obtained at a relatively low voltage, termed the critical voltage. Furthermore, at the critical voltage of 7.5 V, the hybrid microchannel is demonstrated to be capable of separating CTCs from different WBC subtypes including granulocytes, monocytes, T‐, and B‐lymphocytes. The unique capabilities of the hybrid spiral microchannel allow for this size‐independent isolation of CTCs from a mixture of WBCs. Overall, the proposed technique can be readily utilized for continuous and high‐throughput separation of cancer cells.
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