Abstract
Detection of malignant tumor cells (MTCs) in pleural effusions is essential for determining the malignancy. However, the sensitivity of MTC detection is significantly decreased due to the existence of a massive number of background blood cells in large-volume samples. Herein, we provide a method for on-chip separation and enrichment of MTCs from malignant pleural effusions (MPEs) by integrating an inertial microfluidic sorter with an inertial microfluidic concentrator. The designed sorter and concentrator are capable of focusing cells toward the specified equilibrium positions by inducing intrinsic hydrodynamic forces, enabling the size-based sorting of cells and the removal of cell-free fluids for cell enrichment. A 99.9% removal of background cells and a nearly 1400-fold ultrahigh enrichment of MTCs from large-volume MPEs can be achieved by this method. The concentrated high-purity MTC solution can be used directly for cytological examination by immunofluorescence staining, enhancing the accurate identification of MPEs. The proposed method can also be employed for the detection and count of rare cells in various clinical samples.
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References
Baburaj G, Damerla RR, Udupa KS et al (2020) Liquid biopsy approaches for pleural effusion in lung cancer patients. Mol Biol Rep 47:8179–8187
Sun Y, Hu Y, Wan C et al (2021) Local biomaterial-assisted antitumour immunotherapy for effusions in the pleural and peritoneal cavities caused by malignancies. Biomater Sci 9:6381–6390
Paterson K, Zanivan S, Glasspool R et al (2021) Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip 21:2306–2329
Jiang R, Agrawal S, Aghaamoo M et al (2021) Rapid isolation of circulating cancer associated fibroblasts by acoustic microstreaming for assessing metastatic propensity of breast cancer patients. Lab Chip 21:875–887
Wu C-G, Chiovaro F, Curioni A et al (2020) In vitro cell culture of patient derived malignant pleural and peritoneal effusions for personalised drug screening. J Transl Med 18:163
Pillai V, Cibas ES, Dorfman DM (2013) A simplified flow cytometric Immunophenoty** procedure for the diagnosis of effusions caused by epithelial malignancies. Am J Clin Pathol 139:672–681
Billah S, Stewart J, Staerkel G et al (2011) EGFR and KRAS mutations in lung carcinoma molecular testing by using cytology specimens. Cancer Cytopathol 119:111–117
Psallidas I, Kalomenidis I, Porcel JM et al (2016) Malignant pleural effusion: from bench to bedside. Eur Respir Rev 25:189–198
Chen J, Li J, Sun Y (2012) Microfluidic approaches for cancer cell detection, characterization, and separation. Lab Chip 12:1753–1767
Sun J, Gao L, Wang L et al (2021) Recent advances in single-cell analysis: encapsulation materials, analysis methods and integrative platform for microfluidic technology. Talanta 234:122671
Zhu S, Fang Y, Chen Y et al (2022) Stackable micromixer with modular design for efficient mixing over wide Reynold numbers. Int J Heat Mass Tran 183:122129
Hu D, Liu H, Tian Y et al (2020) Sorting Technology for Circulating Tumor Cells Based on microfluidics. ACS Comb Sci 22:701–711
Zhu S, Jiang F, Han Y et al (2020) Microfluidics for label-free sorting of rare circulating tumor cells. Analyst 145:7103–7124
Tang W, Zhu S, Jiang D et al (2020) Channel innovations for inertial microfluidics. Lab Chip 20:3485–3502
Chen Y, Zhou Z, Zhu S et al (2022) Label-free microfluidics for single-cell analysis. Microchem J 177:107284
Zhu S, Zhang X, Zhou Z et al (2021) Microfluidic impedance cytometry for single-cell sensing: review on electrode configurations. Talanta 233:122571
Zhou Z, Chen Y, Zhu S et al (2021) Inertial microfluidics for high-throughput cell analysis and detection: a review. Analyst 146:6064–6083
Song Y, Han X, Li D et al (2021) Simultaneous and continuous particle separation and counting via localized DC-dielectrophoresis in a microfluidic chip. RSC Adv 11:3827–3833
Li P, Zhong J, Liu N et al (2021) Physical properties-based microparticle sorting at submicron resolution using a tunable acoustofluidic device. Sens Actuators B Chem 344:130203
Ning S, Liu S, **ao Y et al (2021) A microfluidic chip with a serpentine channel enabling high-throughput cell separation using surface acoustic waves. Lab Chip 21:4608–4617
Lu X, Liu C, Hu G et al (2017) Particle manipulations in non-Newtonian microfluidics: a review. J Colloid Interface Sci 500:182–201
Zhu Z, Wu D, Li S et al (2021) A polymer-film inertial microfluidic sorter fabricated by jigsaw puzzle method for precise size-based cell separation. Anal Chim Acta 1143:306–314
Ren H, Zhu Z, **ang N et al (2021) Multiplexed serpentine microchannels for high-throughput sorting of disseminated tumor cells from malignant pleural effusion. Sens Actuators B Chem 337:129758
Zhu S, Zhang X, Chen M et al (2021) An easy-fabricated and disposable polymer-film microfluidic impedance cytometer for cell sensing. Anal Chim Acta:1175
Zhu Z, Li S, Wu D et al (2022) High-throughput and label-free enrichment of malignant tumor cells and clusters from pleural and peritoneal effusions using inertial microfluidics. Lab Chip 22:2097–2106
**ang N, Ni Z (2022) High-throughput concentration of rare malignant tumor cells from large-volume effusions by multistage inertial microfluidics. Lab Chip 22:757–767
Acknowledgments
This research work is supported by the National Natural Science Foundation of China (51875103) and the Natural Science Foundation of Jiangsu Province (BK20190064).
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Ni, C., Zhu, Z., Zhou, Z., **ang, N. (2023). High-Throughput Separation and Enrichment of Rare Malignant Tumor Cells from Large-Volume Effusions by Inertial Microfluidics. In: Garcia-Cordero, J.L., Revzin, A. (eds) Microfluidic Systems for Cancer Diagnosis . Methods in Molecular Biology, vol 2679. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3271-0_13
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DOI: https://doi.org/10.1007/978-1-0716-3271-0_13
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