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Analysis of red blood cell deformability using parallel ladder electrodes in a microfluidic manipulation system

  • Wanting Li
  • Botao Zhu
  • Yifan Cai
  • Zhengtian Wu
  • Lining Sun
  • Hao YangEmail author
ORIGINAL ARTICLE
  • 76 Downloads

Abstract

The mechanical properties of biological cells are known as effective label-free biomarkers in many cell physiological events. Several techniques have been proposed to manipulate, measure, and analyze cell mechanical properties, including micropipette aspiration, atomic force microscopy, optical tweezers, and magnetic tweezers. However, most of these methods have inherent problems in practice, including high equipment cost, complex operation, low accuracy, and low throughput. This paper presents a new method for the mechanical characterization of red blood cells (RBCs) on the basis of a dielectrophoresis (DEP) microfluidic system integrated with newly designed parallel ladder electrodes. The proposed microfluidic system not only can stretch RBCs in single-cell level exactly but also has the advantages of high efficiency and throughput. The DEP force generated by the ITO electrodes was theoretically studied, and a series of experiments were performed to stretch RBCs. The relationship between the DEP force and the strain of the RBCs was analyzed, which elucidated the elongation process of RBC under the domination of DEP force, as well as the maximum elongation ability of RBCs. These quantitative results are helpful for people to understand the characteristics of RBCs.

Keywords

Dielectrophoresis Red blood cells Mechanical properties DEP force 

Notes

Funding information

This research was supported in part by a grant from the National Natural Science Foundation of China, Grant Number 61703294; a grant from the Natural Science Foundation of Jiangsu Province, Grant Number BK20170342; grants from China Postdoctoral Science Foundation, Grant Number 2017M611897.

References

  1. 1.
    Sens P, Plastino J (2015) Membrane tension and cytoskeleton organization in cell motility. J Phys Condens Matter 27(27):273103CrossRefGoogle Scholar
  2. 2.
    Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463:485–492CrossRefGoogle Scholar
  3. 3.
    Coughlin MF, Bielenberg DR, Lenormand G, Marinkovic M, Waghorne CG, Zetter BR, Fredberg JJ (2013) Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin Exp Metastas 30(3):237–250CrossRefGoogle Scholar
  4. 4.
    Rathje LSZ, Nordgren N, PetterssonT RND, Widengren J, AspenströM P, Gad AKB (2014) Oncogenes induce a vimentin filament collapse mediated by hdac6 that is linked to cell stiffness. Proc Natl Acad Sci U S A 111:1515–1520CrossRefGoogle Scholar
  5. 5.
    Ofek G, Willard VP, Koay EJ, Hu JC, Lin P, Athanasiou KA (2009) Mechanical characterization of differentiated human embryonic stem cells. J Biomech Eng 131(6):061011CrossRefGoogle Scholar
  6. 6.
    Dino DC (2012) A mechanical biomarker of cell state in medicine. J Lab Autom 17:32–42CrossRefGoogle Scholar
  7. 7.
    Amberg D, Leadsham JE, Kotiadis V, Gourlay CW (2012) Cellular ageing and the actin cytoskeleton. Subcell Biochem 57:331–352CrossRefGoogle Scholar
  8. 8.
    Sures S, Spatz J, Mills JP, Micoulet A, Dao M, Lim CT, Beil M, Seufferlein T (2005) Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater 1(1):15–30CrossRefGoogle Scholar
  9. 9.
    Park YK, Best CA, Badizadegan K, Dasari RR, Feld MS, Kuriabova T, Henle ML, Levine AJ, Popescu G (2010) Measurement of red blood cell mechanics during morphological changes. PNAS 107(15):6731–6736CrossRefGoogle Scholar
  10. 10.
    Maciaszek JL, Lykotrafitis G (2011) Sickle cell trait human erythrocytes are significantly stiffer than normal. J Biomech 44:657–661CrossRefGoogle Scholar
  11. 11.
    Discher DE, Mohandas N, Evans EA (1994) Molecular maps of red cell deformation: hidden elasticity and in situ connectivity. Science 266:1032–1035CrossRefGoogle Scholar
  12. 12.
    Carvalho PA, Diez-Silva M, Chen H, Dao M, Suresh S (2013) Cytoadherence of erythrocytes invaded by plasmodium falciparum: quantitative contact-probing of a human malaria receptor. Acta Biomater 9(5):6349–6359CrossRefGoogle Scholar
  13. 13.
    Mills JP, Qie L, Dao M, Lim CT, Suresh S (2004) Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers. Mech Chem Biosyst 1(3):169–180Google Scholar
  14. 14.
    Puig-de-Morales-Marinkovic M, Turner KT, Butler JP, Fredberg JJ, Suresh S (2007) Viscoelasticity of the human red blood cell. Am J Physiol Cell Physiol 293:597–605CrossRefGoogle Scholar
  15. 15.
    Ford AJ, Rajagopalan P (2018) Measuring cytoplasmic stiffness of fibroblasts as a function of location and substrate rigidity using atomic force microscopy. Acs Biomater Sci Eng 4(12):3974–3982CrossRefGoogle Scholar
  16. 16.
    Addae-Mensah KA, Wikswo JP (2008) Measurement techniques for cellular biomechanics in vitro. Exp Biol Med (Maywood) 233(7):792–809CrossRefGoogle Scholar
  17. 17.
    Du E, Dao M, Suresh S (2014) Quantitative biomechanics of healthy and diseased human red blood cells using dielectrophoresis in a microfluidic system. Extreme Mech Lett 1:35–41CrossRefGoogle Scholar
  18. 18.
    Lee DW, Il D, Kuypers FA, Cho YH (2015) Sub-population analysis of deformability distribution in heterogeneous red blood cell population. Biomed Microdevices 17:102CrossRefGoogle Scholar
  19. 19.
    Bai GH, Li Y, Chu HK, Wang KQ, Tan QL, Xiong JJ, Sun D (2017) Characterization of biomechanical properties of cells through dielectrophoresis-based cell stretching and actin cytoskeleton modeling. Biomed Eng Online 16:41CrossRefGoogle Scholar
  20. 20.
    Teng Y, Zhu K, Xiong CY, Huang JY (2018) Electrodeformation-based biomechanical chip for quantifying global viscoelasticity of cancer cells regulated by cell cycle. Anal Chem 90:8370–8837CrossRefGoogle Scholar
  21. 21.
    Qiang YH, Liu J, Du E (2018) Dielectrophoresis testing of nonlinear viscoelastic behaviors of human red blood cells. Micromachines 9:21CrossRefGoogle Scholar
  22. 22.
    Pohl HA (1951) The motion and precipitation of suspensoids in divergent electric fields. J Appl Phys 22:869–871CrossRefGoogle Scholar
  23. 23.
    Jones TB (1995) Electromechanics of particles. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  24. 24.
    Chen J, Abdelgawad M, Yu LM, Shakiba N, Chien WY, Lu Z, Geddie WR, Jewett MAS, Sun Y (2011) Electrodeformation for single cell mechanical characterization. J Micromech Microeng 21(5):054012CrossRefGoogle Scholar
  25. 25.
    Zhang XF, Chu HK, Zhang Y, Bai GH, Wang KQ, Tan QL, Sun D (2015) Rapid characterization of the biomechanical properties of drug-treated cells in a microfluidic device. J Micromech Microeng 25:105004CrossRefGoogle Scholar
  26. 26.
    Taff BM, Voldman J (2005) A scalable addressable positive-dielectrophoretic cell-sorting array. Anal Chem 77:7976–7983CrossRefGoogle Scholar
  27. 27.
    Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH, Farrell K, Manger ID, Daridon A (2003) Microfluidic device for single-cell analysis. Anal Chem 75:3581–3586CrossRefGoogle Scholar
  28. 28.
    Li FF, Chan CU, Ohl CD (2013) Yield strength of human erythrocyte membranes to impulsive stretching. Biophys J 105:872–879CrossRefGoogle Scholar
  29. 29.
    Wu Z, Karimi HR, Dang C (2019) An approximation algorithm for graph partitioning via deterministic annealing neural network. Neural Netw 117:191–200CrossRefGoogle Scholar
  30. 30.
    Wu Z, Jiang B, Kao Y (2019) Finite-time H∞ filtering for Itô stochastic Markovian jump systems with distributed time-varying delays based on optimisation algorithm. IET Control Theory Appl 13(5):702–710MathSciNetCrossRefGoogle Scholar
  31. 31.
    Tomaiuolo G (2014) Biomechanical properties of red blood cells in health and disease towards microfluidics. Biomicrofluidics 8:051501CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Robotics and Microsystems Center, School of Mechanical and Electric EngineeringSoochow UniversitySuzhouPeople’s Republic of China
  2. 2.Suzhou University of Science and TechnologySuzhouPeople’s Republic of China

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