Mechanical modeling characterization of biological cells using microrobotics cell injection test bed

Mechanical properties of biological cells play an important role in regulating cellular functions. Some micromanipulation methods have been reported in the literature to measure cell mechanics, but they are either high-costly or difficultly-operated. This paper presents our approach to use microrobotic cell injection technology as the test bed to characterize the mechanical properties of biological cells, by virtue of low cost and easy operation. By extending our previous work [41], we develop a mechanical model to interpret the mechanical responses during microinjection and extract the cells properties. Both finite element analysis and microinjection experiments are performed to verify the mechanical model. It is shown that the results obtained from the proposed mechanical model agree well with that obtained from finite element analysis and the experiments. Elastic moduli of zebrafish embryos at different developmental stages are characterized. This demonstrates not only the validity of the proposed model but also the fact that the microrobotic cell injection technology combining with the mechanical model can be used to characterize the mechanical properties of biological cells.

[1]  G I Zahalak,et al.  Cell poking. Determination of the elastic area compressibility modulus of the erythrocyte membrane. , 1984, Biophysical journal.

[2]  Yu Sun,et al.  A Fully Automated Robotic System for Microinjection of Zebrafish Embryos , 2007, PloS one.

[3]  N Xi,et al.  Force measurement and mechanical characterization of living Drosophila embryos for human medical study , 2007, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[4]  S. Hénon,et al.  A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers. , 1999, Biophysical journal.

[5]  A. Iritani,et al.  Micromanipulation of gametes for in vitro assisted fertilization , 1991, Molecular reproduction and development.

[6]  R. W. Bernstein,et al.  Microoptical characterization and modeling of positioning forces on drosophila embryos self-assembled in two-dimensional arrays , 2005, Journal of Microelectromechanical Systems.

[7]  Haibo Huang,et al.  Integrated vision and force control in suspended cell injection system: Towards automatic batch biomanipulation , 2008, 2008 IEEE International Conference on Robotics and Automation.

[8]  T. J. Lardner,et al.  XII – Compression of Spherical Cells , 1980 .

[9]  L Y Cheng.  Deformation analyses in cell and developmental biology. Part I--Formal methodology. , 1987, Journal of biomechanical engineering.

[10]  L. Fausett.  Numerical Methods: Algorithms and Applications , 2002 .

[11]  Z. Stachura,et al.  Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy , 1999, European Biophysics Journal.

[12]  Kok-Kiong Tan,et al.  Optimal intra-cytoplasmic sperm injection with a piezo micromanipulator , 2002, Proceedings of the 4th World Congress on Intelligent Control and Automation (Cat. No.02EX527).

[13]  Bradley J. Nelson,et al.  Microrobotic cell injection , 2001, Proceedings 2001 ICRA. IEEE International Conference on Robotics and Automation (Cat. No.01CH37164).

[14]  Stefan Schinkinger,et al.  Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. , 2005, Biophysical journal.

[15]  R. Simmons,et al.  Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study. , 1999, Biophysical journal.

[16]  C. Lim,et al.  AFM indentation study of breast cancer cells. , 2008, Biochemical and biophysical research communications.

[17]  S. Timoshenko,et al.  Theory of elasticity , 1975 .

[18]  Peter C. Y. Chen,et al.  A micromanipulation system with dynamic force-feedback for automatic batch microinjection , 2007 .

[19]  Haibo Huang,et al.  Visual-based Impedance Force Control of Three-dimensional Cell Injection System , 2007, Proceedings 2007 IEEE International Conference on Robotics and Automation.

[20]  P. Kallio,et al.  Challenges in capillary pressure microinjection , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[21]  W. W. Feng,et al.  On the Contact Problem of an Inflated Spherical Nonlinear Membrane , 1973 .

[22]  Ferenc Horkay,et al.  Determination of elastic moduli of thin layers of soft material using the atomic force microscope. , 2002, Biophysical journal.

[23]  David Barlam,et al.  Mechanical properties of murine leukemia virus particles: effect of maturation. , 2006, Biophysical journal.

[24]  C. Shih,et al.  Cell motility and local viscoelasticity of fibroblasts. , 2005, Biophysical journal.

[25]  E. Sackmann,et al.  Measurement of local viscoelasticity and forces in living cells by magnetic tweezers. , 1999, Biophysical journal.

[26]  Farshid Guilak,et al.  A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: do cell properties reflect metastatic potential? , 2007, Biophysical journal.

[27]  Haibo Huang,et al.  Robotic Cell Injection System With Position and Force Control: Toward Automatic Batch Biomanipulation , 2009, IEEE Transactions on Robotics.

[28]  Ben Fabry,et al.  Microrheology of human lung epithelial cells measured by atomic force microscopy. , 2003, Biophysical journal.

[29]  A. Mehta,et al.  Single-molecule biomechanics with optical methods. , 1999, Science.

[30]  J. Rao,et al.  Nanomechanical analysis of cells from cancer patients. , 2007, Nature nanotechnology.

[31]  Kok Kiong Tan,et al.  Optimal Intra-Cytoplasmic Sperm Injection with a Piezo Micromanipulator , 2004, Control. Intell. Syst..

[32]  Michael A. Ferenczi,et al.  A micromanipulation technique with a theoretical cell model for determining mechanical properties of single mammalian cells , 1992 .

[33]  Yu Xie,et al.  A force control based cell injection approach in a bio-robotics system , 2009, 2009 IEEE International Conference on Robotics and Automation.

[34]  Williams,et al.  Compressive deformation of a single microcapsule. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[35]  N O Petersen,et al.  Dependence of locally measured cellular deformability on position on the cell, temperature, and cytochalasin B. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Cowman,et al.  Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells. , 2002, Blood.

[37]  S. Zimmer,et al.  Viscoelastic properties of transformed cells: role in tumor cell progression and metastasis formation. , 1991, Biorheology.

[38]  Shusheng Bi,et al.  Development of global vision system for biological automatic micro-manipulation system , 2001, Proceedings 2001 ICRA. IEEE International Conference on Robotics and Automation (Cat. No.01CH37164).

[39]  D A Lauffenburger,et al.  Simulation of integrin-cytoskeletal interactions in migrating fibroblasts. , 1994, Biophysical journal.

[40]  Michael Beil,et al.  Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells , 2003, Nature Cell Biology.

[41]  Haibo Huang,et al.  Visual-Based Impedance Control of Out-of-Plane Cell Injection Systems , 2009, IEEE Transactions on Automation Science and Engineering.

[42]  Edward Grant,et al.  Semi-automated blastocyst microinjection , 2006, Proceedings 2006 IEEE International Conference on Robotics and Automation, 2006. ICRA 2006..

[43]  Dong Sun,et al.  Mechanical Modeling of Biological Cells in Microinjection , 2008, IEEE Transactions on NanoBioscience.

[44]  Yantao Shen,et al.  In situ micro-force sensing and quantitative elasticity evaluation of living Drosophila embryos at different stages , 2008, 2008 IEEE/ASME International Conference on Advanced Intelligent Mechatronics.

[45]  J. Käs,et al.  The optical stretcher: a novel laser tool to micromanipulate cells. , 2001, Biophysical journal.

[46]  R M Hochmuth,et al.  Membrane viscoelasticity. , 1976, Biophysical journal.

[47]  Subra Suresh,et al.  Nanomedicine: elastic clues in cancer detection. , 2007, Nature nanotechnology.

[48]  Ehsan Gazi,et al.  Measurement of elastic properties of prostate cancer cells using AFM. , 2008, The Analyst.

[49]  O. Thoumine,et al.  Time scale dependent viscoelastic and contractile regimes in fibroblasts probed by microplate manipulation. , 1997, Journal of cell science.