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A Novel Approach for Tuning of Fluidic Resistance in Deterministic Lateral Displacement Array for Enhanced Separation of Circulating Tumor Cells

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Abstract

Deterministic lateral displacement (DLD) is evolving as an effective passive technique for seclusion of circulating tumor cells (CTCs) functioning based on nonuniform splitting of laminar flow moving through an array of micropillars. In this research work, an unconventional approach has been presented to alter the fluidic resistance between micropillars in asymmetric DLD array for better separation of CTCs in a blood sample. This paper is aimed at introducing an innovative approach using electrical network analogy for tuning of fluidic resistance resulting in enhanced seclusion of CTCs from WBCs implementing the concept of asymmetric DLD array. The paper also describes the computational analysis of a microfluidic device using tuned asymmetric DLD array technique. A cognitive clinical decision support system for identification of CTCs based on the model is also illustrated. In this paper, computational fluid dynamics approach has been used through simulation of the microfluidic device in COMSOL Multiphysics 5.4 software to effectively regulate the trajectory of differently sized CTCs and WBCs. A novel mathematical fluidic resistance tuning approach has been introduced to design the DLD array for effective segregation of different varieties of CTCs realized by computational visualization of trajectory working on Navier–Stokes equation. The proposed design of microfluidic device isolates three distinct CTCs, i.e., lung cancer CTCs, prostate cancer CTCs, and breast cancer CTCs of diameters 22.5 µm, 10.64 µm, and 13.1 µm, respectively, from tiny WBCs of diameter 12 µm with separation efficiencies above 90% at a high sample flow rate of 20 × 10−6 kg/s, thereby offering higher throughput. The tuning model of fluidic resistances between micropillars has been shown to offer minimal resistive effect to the required CTC trajectory while maintaining uniform pressure distribution around micropillars.

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References

  1. Dong Y, Skelley AM, Merdek KD, Sprott KM, Jiang C, Pierceall WE, Lin J, Stocum M, Carney WP, Smirnov DA. Microfluidics and circulating tumor cells. J Mol Diagn. 2013;15(2):149–57.

    Article  Google Scholar 

  2. Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010;617421.

  3. Bouche O, Beretta GD, Alfonso PG, Geissler M. The role of anti-epidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer. Cancer Treat Rev. 2010;36(Suppl 1):S1–10.

    Article  Google Scholar 

  4. den Toonder J. Circulating tumor cells: the Grand Challenge. Lab Chip. 2011;11:375–7.

    Article  Google Scholar 

  5. Mahmud M, Kaiser MS, McGinnity TM, Hussain A. Deep learning in mining biological data. Cogn Comput. 2021;13(1):1–33.

    Article  Google Scholar 

  6. Faundez-Zanuy M, Fierrez J, Ferrer MA, Diaz M, Tolosana R, Plamondon R. Handwriting biometrics: Applications and future trends in e-security and e-health. Cogn Comput. 2020;12(5):940–53.

    Article  Google Scholar 

  7. Deebak BD, Al-Turjman F. Smart mutual authentication protocol for cloud based medical healthcare systems using Internet of medical things. IEEE Journal on Selected Areas in Communications. 2020.

  8. Jin, et al. Technologies for label-free separation of circulating tumor cells: from historical foundations to recent developments. Lab Chip. 2014;14(1):32–44.

    Article  Google Scholar 

  9. Meng, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10(24):8152–62.

    Article  Google Scholar 

  10. Park S, et al. Morphological differences between circulating tumor cells from prostate cancer patients and cultured prostate cancer cells. PLoS One. 2014;9(1):e85264.

  11. Allard WJ, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10(20):6897–904.

    Article  Google Scholar 

  12. Thiele J, Bethel K, Králíčková M, Kuhn P. Circulating tumor cells: fluid surrogates of solid tumors. Annu Rev Pathol. 2017;12:419–47.

    Article  Google Scholar 

  13. Yang M, et al. Incorporating blood-based liquid biopsy information into cancer staging: time for a TNMB system? Ann Oncol. 2017;29(2):311–23.

    Article  Google Scholar 

  14. Songjaroen T, Dungchai W, Chailapakul O, Henry CS, Laiwattanapaisal W. Blood separation on microfluidic paper-based analytical devices. Lab Chip. 2012;12:3392–8.

    Article  Google Scholar 

  15. Kim J-H, Woenker T, Adamec J, Regnier FE. Simple, miniaturized blood plasma extraction method. Anal Chem. 2013;85:11501–8.

    Article  Google Scholar 

  16. Haeberle S, Brenner T, Zengerle R, Ducrée J. Centrifugal extraction of plasma from whole blood on a rotating disk. Lab Chip. 2006;6:776–81.

    Article  Google Scholar 

  17. Amasia M, Madou M. Large-volume centrifugal microfluidic device for blood plasma separation. Bioanalysis. 2010;2:1701–10.

    Article  Google Scholar 

  18. Kersaudy-Kerhoas M, Sollier E. Micro-scale blood plasma separation: from acoustophoresis to egg-beaters. Lab Chip. 2013;13:3323–46.

    Article  Google Scholar 

  19. Witek MA, Freed IM, Soper SA. Cell separations and sorting. Anal Chem. 2019;92(1):105–31.

    Article  Google Scholar 

  20. Ishikawa T, Fujiwara H, Matsuki N, Yoshimoto T, Imai Y, Ueno H, Yamaguchi T. Asymmetry of blood flow and cancer cell adhesion in a microchannel with symmetric bifurcation and confluence. Biomed Microdevices. 2011;13:159–67.

    Article  Google Scholar 

  21. Karimi A, Yazdi S, Ardekani AM. Hydrodynamic mechanisms of cell and particle trapping in microfluidics. Biomicrofluidics. 2013;7:21501.

    Article  Google Scholar 

  22. Zhang J, Yan S, Yuan D, Alici G, Nguyen NT, Warkiani ME, Li W. Fundamentals and applications of inertial microfluidics: A review. Lab Chip. 2016;16:10–34.

    Article  Google Scholar 

  23. Pødenphant M1, Ashley N, Koprowska K, Mir KU, Zalkovskij M, Bilenberg B, Bodmer W, Kristensen A, Marie R. Separation of cancer cells from white blood cells by pinched flow fractionation. Lab Chip. 2015;15(24):4598–4606.

  24. Yoon Y, Lee J, Ra M, Gwon H, Lee S, Kim MY, Yoo K-C, Sul O, Kim CG, Kim W-Y, Park J-G, Lee S-J, Lee YY, Choi HS, Lee S-B. Continuous separation of circulating tumor cells from whole blood using a slanted weir microfluidic device. Cancers. 2019;11(2):200.

    Article  Google Scholar 

  25. Dharmasiri U, Njoroge SK, Witek MA, Adebiyi MG, Kamande JW, Hupert ML, Barany F, Soper SA. High-throughput selection, enumeration, electrokinetic manipulation, and molecular profiling of low-abundance circulating tumor cells using a microfluidic system. Anal Chem. 2011;83(6):2301–9.

    Article  Google Scholar 

  26. Johnson ES, Anand RK, Chiu DT. Improved detection by ensemble-decision aliquot ranking of circulating tumor cells with low numbers of a targeted surface antigen. Anal Chem. 2015;87(18):9389–95.

    Article  Google Scholar 

  27. Kumar V, Rezai P. Magneto-hydrodynamic fractionation (MHF) for continuous and sheathless sorting of high-concentration paramagnetic microparticles. Biomed Microdevices. 2017;19:39.

    Article  Google Scholar 

  28. Salafi T, Zhang Y, Zhang Y. A review on deterministic lateral displacement for particle separation and detection. Nano-Micro Lett. 2019;11:77.

    Article  Google Scholar 

  29. Kottmeier J. Maike Wullen weber, Sebastian Blahout, Jeanette Hussong, Ingo Kampen, Arno Kwade and Andreas Dietzel, Accelerated particle separation in a DLD device at Re > 1 investigated by means of µPIV. Micromachines. 2019;10:768.

    Article  Google Scholar 

  30. Zeming K, Salafi T, Chen C, et al. Asymmetrical deterministic lateral displacement gaps for dual functions of enhanced separation and throughput of red blood cells. Sci Rep. 2016;6:22934.

    Article  Google Scholar 

  31. Inglis D, Vernekar R, Krüger T, et al. The fluidic resistance of an array of obstacles and a method for improving boundaries in deterministic lateral displacement arrays. Microfluid Nanofluid. 2020;24(3):18.

  32. Fachin F, Spuhler P, Martel-Foley JM, et al. Monolithic chip for high-throughput blood cell depletion to sort rare circulating tumor cells. Sci Rep. 2017;7:10936.

    Article  Google Scholar 

  33. Phillips KG, et al. Optical quantification of cellular mass, volume, and density of circulating tumor cells identified in an ovarian cancer patient. Front Oncol. 2012;2:72.

  34. Zhou J, Kulasinghe A, Bogseth A, et al. Isolation of circulating tumor cells in non-small-cell-lung-cancer patients using a multi-flow microfluidic channel. Microsyst Nanoeng. 2019;5(8).

  35. Qin L, et al. Highly Efficient Isolation of Circulating Tumor Cells Using a Simple Wedge-Shaped Microfluidic Device. IEEE Trans Biomed Eng. 2019;66(6):1536–41.

    Article  Google Scholar 

  36. Liu Z, Chen R, Li Y, Liu J, Wang P, Xia X, Qin L. Integrated microfluidic chip for efficient isolation and deformability analysis of circulating tumor cells. Adv Biosyst. 2018;2(10):1800200.

    Article  Google Scholar 

  37. González-Esparza D, Del Angel-Arroyo JA, Elvira-Hernández EA, Herrera-May AL, Aguilera-Cortés LA. Design and modeling of a microfluidic device with potential application for isolation of circulating tumor cells. IEEE International Conference on Engineering Veracruz (ICEV), Boca del Rio, Veracruz, Mexico. 2019;1–7.

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Authors and Affiliations

  1. Department of Electronics and Instrumentation Engineering, National Institute of Technology Nagaland, Dimapur, 797103, Nagaland, India

    Rituraj Bhattacharjee & R. Kumar

  2. Artificial Intelligence Engineering Dept, Research Centre for AI and IoT, Near East University, Nicosia, Mersin 10, Turkey

    Fadi Al-Turjman

Authors
  1. Rituraj Bhattacharjee
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  2. R. Kumar
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  3. Fadi Al-Turjman
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Correspondence to R. Kumar.

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Bhattacharjee, R., Kumar, R. & Al-Turjman, F. A Novel Approach for Tuning of Fluidic Resistance in Deterministic Lateral Displacement Array for Enhanced Separation of Circulating Tumor Cells. Cogn Comput 14, 1660–1676 (2022). https://doi.org/10.1007/s12559-021-09904-y

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