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Deformation and focusing of hydrogel microparticles in microfluidic flow: mimicking the segregation of cancer cells with similar sizes

Published online by Cambridge University Press:  21 March 2025

Zhenya Ding
Affiliation:
Department of Mechanics and Aerospace Engineering & Center for Complex Flows and Soft Matter Research, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China
Yihao Xiao
Affiliation:
Department of Mechanics and Aerospace Engineering & Center for Complex Flows and Soft Matter Research, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China
Hua Zhang
Affiliation:
Department of Mechanics and Aerospace Engineering & Center for Complex Flows and Soft Matter Research, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China Department of Mechanical Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Republic of Singapore
Keyao Zhang
Affiliation:
Department of Mechanics and Aerospace Engineering & Center for Complex Flows and Soft Matter Research, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China
Chi Zhu
Affiliation:
Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, PR China
Lian-Ping Wang
Affiliation:
Department of Mechanics and Aerospace Engineering & Center for Complex Flows and Soft Matter Research, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China
Yahui Xue*
Affiliation:
Department of Mechanics and Aerospace Engineering & Center for Complex Flows and Soft Matter Research, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China
*
Corresponding author: Yahui Xue, [email protected]

Abstract

The demand for separating and analysing rare target cells is increasing dramatically for vital applications such as cancer treatment and cell-based therapies. However, there remains a grand challenge for high-throughput and label-free segregation of lesion cells with similar sizes. Cancer cells with different invasiveness usually manifest distinct deformability. In this work, we employ a hydrogel microparticle system with similar sizes but varied stiffness to mimic cancer cells and examine in situ their deformation and focusing under microfluidic flow. We first demonstrate the similar focusing behaviour of hydrogel microparticles and cancer cells in confined flow that is dominated by deformability-induced lateral migration. The deformation, orientation and focusing position of hydrogel microparticles in microfluidic flow under different Reynolds numbers are then systematically observed and measured using a high-speed camera. Linear correlations of the Taylor deformation and tilt angle of hydrogel microparticles with the capillary number are revealed, consistent with theoretical predictions. Detailed analysis of the dependence of particle focusing on the flow rate and particle stiffness enables us to identify a linear scaling between the equilibrium focusing position and the major axis of the deformed microparticles, which is uniquely determined by the capillary number. Our findings provide insights into the focusing and dynamics of soft beads, such as cells and hydrogel microparticles, under confined flow, and pave the way for applications including the separation and identification of circulating tumour cells, drug delivery and controlled drug release.

Type
JFM Papers
Copyright
© The Author(s), 2025. Published by Cambridge University Press

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References

Alghalib, D., Rosti, M.E. & Brandt, L. 2019 Inertial migration of a deformable particle in pipe flow. Phys. Rev. Fluids 4 (10), 104201.CrossRefGoogle Scholar
Amini, H., Lee, W. & Di Carlo, D. 2014 Inertial microfluidic physics. Lab on a Chip 14 (15), 27392761.CrossRefGoogle ScholarPubMed
Asmolov, E.S. 1999 The inertial lift on a spherical particle in a plane Poiseuille flow at large channel Reynolds number. J. Fluid Mech. 381, 6387.CrossRefGoogle Scholar
Bayareh, M. 2020 An updated review on particle separation in passive microfluidic devices. Chem. Engng Process 153, 107984.CrossRefGoogle Scholar
Choi, Y.H., Kim, J.A. & Lee, W. 2020 Changes of inertial focusing position in a triangular channel depending on droplet deformability and size. Micromachines 11 (9), 839.CrossRefGoogle Scholar
Chrit, F.E., Bowie, S. & Alexeev, A. 2020 Inertial migration of spherical particles in channel flow of power law fluids. Phys. Fluids 32 (8), 083103.CrossRefGoogle Scholar
Chun, B. & Ladd, A.J.C. 2006 Inertial migration of neutrally buoyant particles in a square duct: an investigation of multiple equilibrium positions. Phys. Fluids 18 (3), 031704.CrossRefGoogle Scholar
Clausen, J.R. & Aidun, C.K. 2010 Capsule dynamics and rheology in shear flow: particle pressure and normal stress. Phys. Fluids 22 (12), 123302–123301.CrossRefGoogle Scholar
Connolly, S., McGourty, K. & Newport, D. 2021 The influence of cell elastic modulus on inertial positions in Poiseuille microflows. Biophys. J. 120, 855865.CrossRefGoogle ScholarPubMed
Daniel, C., Traub, F., Sachsenmaier, S., Riester, R., Mederake, M., Konrads, C. & Danalache, M. 2023 An exploratory study of cell stiffness as a mechanical label-free biomarker across multiple musculoskeletal sarcoma cells. BMC Cancer 23 (1), 862.CrossRefGoogle ScholarPubMed
Debaize, L. et al. 2022 Cell mass and stiffness as integrative biomarkers of cell state in mantle cell lymphoma. Blood 140 (1), 35813582.CrossRefGoogle Scholar
Di Carlo, D. 2009 Inertial microfluidics. Lab on a Chip 9 (21), 30383046.CrossRefGoogle ScholarPubMed
Di Carlo, D., Edd, J.F., Humphry, K.J., Stone, H.A. & Toner, M. 2007 Particle segregation and dynamics in confined flows. Phys. Rev. Lett. 102 (9), 094503.CrossRefGoogle Scholar
Doddi, S.K. & Bagchi, P. 2008 Lateral migration of a capsule in a plane Poiseuille flow in a channel. Intl J. Multiphase Flow 34 (10), 966986.CrossRefGoogle Scholar
Faria, E.C., Ma, N., Gazi, E., Gardner, P., Brown, M., Clarke, N.W. & Snook, R.D. 2008 Measurement of elastic properties of prostate cancer cells using AFM. The Analyst 133 (11), 14981500.CrossRefGoogle ScholarPubMed
Gao, T., Hu, H.H. & Castañeda, P.P. 2013 Dynamics and rheology of elastic particles in an extensional flow. J. Fluid Mech. 715, 573596.CrossRefGoogle Scholar
Ghosh, S. & Goswami, P.S. 2022 Dynamics of particle-laden turbulent Couette flow: turbulence modulation by inertial particles. Phys. Fluids 34 (8), 083325.CrossRefGoogle Scholar
Hakim, M., Khorasheh, F., Alemzadeh, I. & Vossoughi, M. 2021 A new insight to deformability correlation of circulating tumor cells with metastatic behavior by application of a new deformability-based microfluidic chip. Anal. Chim. Acta 1186, 339115.CrossRefGoogle ScholarPubMed
He, Q. et al. 2021 Injectable silk sericin hydrogel for breast reconstruction. Polymers 13, 254.Google Scholar
Hur, S.C., Henderson-MacLennan, N.K., McCabe, E.R.B. & Di Carlo, D. 2011 Deformability-based cell classification and enrichment using inertial microfluidics. Lab on a Chip 11 (5), 912.CrossRefGoogle ScholarPubMed
Hu, X., Lin, J., Guo, Y. & Ku, X. 2021 Inertial focusing of elliptical particles and formation of self-organizing trains in a channel flow. Phys. Fluids 33 (1), 013310.CrossRefGoogle Scholar
Jannesari Ghomsheh, M., Jafari, A. & Funfschilling, D. 2023 Inertial lift on a particle in a straight microchannel of Newtonian, power-law and Carreau-Yasuda fluids: a simulation study toward optimized particle separation. J. Non-Newtonian Fluid Mech. 312, 104977.CrossRefGoogle Scholar
Kiseleva, D., Kolmogorov, V., Cherednichenko, V., Khovantseva, U., Bogatyreva, A., Markina, Y., Gorelkin, P., Erofeev, A. & Markin, A. 2024 Effect of LDL extracted from human plasma on membrane stiffness in living endothelial cells and macrophages via scanning ion conductance microscopy. Cells 13 (4), 358.CrossRefGoogle ScholarPubMed
Krüger, T., Kaoui, B. & Harting, J. 2014 Interplay of inertia and deformability on rheological properties of a suspension of capsules. J. Fluid Mech. 751, 725745.CrossRefGoogle Scholar
Kumar, P. & Misra, R.D.K. 2020 Designing three-dimensional porous scaffolds for biomedical applications using a facile approach for polymer sintering. ACS Appl. Mater. Interfaces 12, 2004720059.Google Scholar
Kurose, R. & Komori, S. 1999 Drag and lift forces on a rotating sphere in a linear shear flow. J. Fluid Mech. 384, 183206.CrossRefGoogle Scholar
Lashgari, I., Picano, F., Breugem, W.P. & Brandt, L. 2014 Laminar, turbulent, and inertial shear-thickening regimes in channel flow of neutrally buoyant particle suspensions. Phys. Rev. Lett. 113 (25), 254502.Google ScholarPubMed
Lauricella, G., Zhou, J., Luan, Q., Papautsky, I. & Peng, Z. 2022 Computational study of inertial migration of prolate particles in a straight rectangular channel. Phys. Fluids 34 (8), 082021.Google Scholar
Lee, K.Y. & Mooney, D.J. 2012 Alginate: properties and biomedical applications. Prog. Polym. Sci. 37 (1), 106126.CrossRefGoogle ScholarPubMed
Li, D., Lu, X., Xuan, X. & Hu, G. 2016 Effects of fluid rheological properties on particle migration in a straight rectangular microchannel. Microfluid Nanofluid 20, 151.Google Scholar
Li, X., Yang, Y., Villareal, S.C., Griffin, K. & Pappas, D. 2022 High-recovery sorting of cancer cells from whole blood via periodic-focusing inertial microchip. Analyst 147 (20), 45364546.CrossRefGoogle ScholarPubMed
Loth, E. & Dorgan, A.J. 2009 An equation of motion for particles of finite Reynolds number and size. Environ. Fluid Mech. 9 (2), 187206.CrossRefGoogle Scholar
Lu, X., Liu, C., Hu, G. & Xuan, X. 2022 Particle manipulations in non-Newtonian microfluidics: a review. J. Colloid Interface Sci. 500, 182201.Google Scholar
Luo, W., Wen, T. & Qu, X. 2024 Tumor immune microenvironment-based therapies in pancreatic ductal adenocarcinoma: time to update the concept. J. Expl Clin. Cancer Res. 43 (1), 8.CrossRefGoogle ScholarPubMed
Martel, J.M. & Toner, M. 2014 Inertial focusing in microfluidics. Annu. Rev. Biomed. Engng 16 (1), 371396.CrossRefGoogle ScholarPubMed
Masaeli, M., Sollier, E., Amini, H., Mao, W., Camacho, K., Doshi, N., Mitragotri, S., Alexeev, A. & Di Carlo, D. 2012 Continuous inertial focusing and separation of particles by shape. Phys. Rev. X 2 (3), 031017.Google Scholar
Matas, J.P., Morris, J.F. & Guazzelli, É. 2004 Inertial migration of rigid spherical particles in Poiseuille flow. J. Fluid Mech. 515, 171195.CrossRefGoogle Scholar
Matas, J.P., Morris, J.F. & Guazzelli, É. 2009 Lateral force on a rigid sphere in large-inertia laminar pipe flow. J. Fluid Mech. 621, 5967.CrossRefGoogle Scholar
Molter, C.W., Muszynski, E.F., Tao, Y. & Trivedi, T. 2022 Prostate cancer cells of increasing metastatic potential exhibit diverse contractile forces, cell stiffness, and motility in a microenvironment stiffness-dependent manner. Frontier Cell Dev. Biol. 10, 932510.CrossRefGoogle Scholar
Molter, C.W., Muszynski, E.F., Tao, Y., Trivedi, T., Clouvel, A. & Ehrlicher, A.J. 2022 Prostate cancer cells of increasing metastatic potential exhibit diverse contractile forces, cell stiffness, and motility in a microenvironment stiffness-dependent manner. Frontier Cell Dev. Biol. 10, 932510.CrossRefGoogle Scholar
Rivlin, R.S. 1948 Large elastic deformations of isotropic materials. IV. Further developments of the general theory. Phil. Trans. Math. Phys. Engng Sci. 241, 379397.Google Scholar
Roscoe, R. 1967 On the rheology of a suspension of viscoelastic spheres in a viscous liquid. J. Fluid Mech. 28 (02), 273293.CrossRefGoogle Scholar
Saez-Ibañez, A.R., Upadhaya, S., Partridge, T., Shah, M., Correa, D. & Campbell, J. 2022 Landscape of cancer cell therapies: trends and real-world data. Nat. Rev. Drug Disc. 21 (9), 631632.CrossRefGoogle ScholarPubMed
Segré, G. & Silberberg, A. 1961 Behaviour of macroscopic rigid spheres in Poiseuille flow. J. Fluid Mech. 14 (1), 136157.CrossRefGoogle Scholar
Smith, A.M. & Moxon, S.R. 2021 Biofabrication of 3D constructs with encapsulated cells using alginate-based hydrogels. Biofabrication 13, 032002.Google Scholar
Sugihara-Seki, M. 1993 The motion of an elliptical cylinder in channel flow at low Reynolds numbers. J. Fluid Mech. 257, 575596.CrossRefGoogle Scholar
Sun, X., Ma, Y., Lu, C., Cai, Z., Han, J., Wang, Z. & Yang, G. 2023 Optimal parameter configuration of a microfluidic chip for high-throughput, label-free circulating tumor cell separation and enrichment based on inertial focusing. Diagnostics 13 (23), 3556.CrossRefGoogle ScholarPubMed
Thorsen, T., Roberts, R.W., Arnold, F.H. & Quake, S.R. 2001 Dynamic pattern formation in a vesicle-generating microfluidic device. Phys. Rev. Lett. 86 (18), 41634166.CrossRefGoogle Scholar
Tohme, T., Magaud, P. & Baldas, L. 2021 Transport of non-spherical particles in square microchannel flows: a review. Micromachines 12 (3), 277.CrossRefGoogle ScholarPubMed
Villone, M.M. & Maffettone, P.L. 2021 Dynamics, rheology, and applications of elastic deformable particle suspensions: a review. Rheol. Acta 58, 109130.CrossRefGoogle Scholar
Weihs, T.P., Lee, P.C. & Kramer, E.M. 1994 Mechanical Properties of Polymethyl Methacrylate (PMMA). NIST Technical Note 1292, National Institute of Standards and Technology.Google Scholar
Williams, P.S., Lee, S. & Giddings, J.C. 1994 Characterization of hydrodynamic lift forces by field-flow fractionation: inertial and near-wall lift forces. Chem. Engng Commun. 130 (1), 143166.CrossRefGoogle Scholar
Xu, X. et al. 2021 Recent progress of inertial microfluidic-based cell separation. Analyst 146 (23), 70707086.CrossRefGoogle ScholarPubMed
Yang, S., Kim, J.Y., Lee, S.J. & Lee, S.S. 2023 Sheathless elasto-inertial particle focusing and continuous separation in a straight rectangular microchannel. Lab on a Chip 16, 794801.Google Scholar
Yu, X., Wang, W., Zhang, B. & Liu, J. 2023 Recent applications of dual-stimuli responsive chitosan hydrogel nanocomposites as drug delivery tools. Molecules 28, 1205.Google Scholar
Zhang, Y. & Wu, B.M. 2023 Current advances in stimuli-responsive hydrogels as smart drug delivery carriers. Gels 9 (10), 838.CrossRefGoogle ScholarPubMed
Zhao, L., Cheng, L. & Yu, Z. 2012 Lattice Boltzmann simulation of particle migration in a channel flow: focusing, ordering, and chain formation. Phys. Fluids 24, 043303.Google Scholar
Zhou, J. & Papautsky, I. 2013 Fundamentals of inertial focusing in microchannels. Lab on a Chip 13 (6), 1121.CrossRefGoogle ScholarPubMed
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