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.
- Award ID(s):
- 1807601
- PAR ID:
- 10112325
- Date Published:
- Journal Name:
- Lab on a Chip
- Volume:
- 19
- Issue:
- 3
- ISSN:
- 1473-0197
- Page Range / eLocation ID:
- 394 to 402
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Rapid and label-free separation of target cells from biological samples provided unique opportunity for disease diagnostics and treatment. However, even with advanced technologies for cell separation, the limited throughput, high cost and low separation resolution still prevented their utility in separating cells with well-defined physical features from a large volume of biological samples. Here we described an ultrahigh-throughput microfluidic technology, termed as inertial-ferrohydrodynamic cell separation (inertial-FCS), that rapidly sorted through over 60 milliliters of samples at a throughput of 100 000 cells per second in a label-free manner, differentiating the cells based on their physical diameter difference with ∼1–2 μm separation resolution. Through the integration of inertial focusing and ferrohydrodynamic separation, we demonstrated that the resulting inertial-FCS devices could separate viable and expandable circulating tumor cells from cancer patients' blood with a high recovery rate and high purity. We also showed that the devices could enrich lymphocytes directly from white blood cells based on their physical morphology without any labeling steps. This label-free method could address the needs of high throughput and high resolution cell separation in circulating tumor cell research and adoptive cell transfer immunotherapy.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/c8lc00527c
