Robotic cell microinjection is a technique that utilizes automation technology to insert substances into a single living cell with a fine needle. Compared with manual microinjection, the main benefits of the robotic cell injection are quality, productivity and repeatability. In this paper we aim to control the penetration force during robotic cell injection to quantify the influence of the penetration force on cells. A force-control-based cell injection approach that is capable of regulating the penetration force in a desired force trajectory is developed. The proposed force control framework includes two control loops. The inner loop is an impedance control used to specify the interaction between the needle and the cell. The outer loop is a force tracking non-linear controller using a feedback linearization technique. The cell model is identified online with a least-squares parameter estimator. With the proposed force control approach, the penetration force can be regulated explicitly to follow the desired force trajectory during the cell injection process. Experiments performed on fish embryos verify the effectiveness of the proposed approach.
Dimaio, S.P. and Salcudean, S.E. ( 2003) Needle insertion modeling and simulation. IEEE Transactions on Robotics, 19: 864-875.
2.
Dumoulin, J., Coonen, E., Bras, M., Bergers-Janssen, J., Ignoul-Vanvuchelen, R., Van Wissen, L., Geraedts, J. and Evers, J. ( 2001) Embryo development and chromosomal anomalies after ICSI: effect of the injection procedure. Journal of Human Reproduction , 16(2): 306-312.
3.
Hogan, N. ( 1985) Impedance control: an approach to manipulation: Part I, II, III. Journal of Dynamical Systems, Measurement, and Control , 107: 1-16.
4.
Huang, H.B., Sun, D., Mills, J.K. and Cheng, S.H.(2009a) Robotics cell injection system with vision and force control: Towards automatic batch biomanipulation. IEEE Transactions on Robotics , 25: 727-737.
5.
Huang, H.B., Sun, D., Mills, J.K. and Li, W.J.(2009b) Visual-based impedance control of out-of-plane cell injection systems . IEEE Transactions on Automation Science and Engineering , 6: 565-571.
6.
Huang, T., Kimura, Y. and Yanagimachi, R. ( 1996) The use of piezo micromanipulation for intracytoplasm sperm injection of human oocytes. Journal of Assisted Reproduction and Genetics, 13: 320-328.
7.
Kallio, P. and Kuncova, J. ( 2004) Capillary pressure microinjection of living adherent cells: challenges in automation. Journal of Micromechatronics, 3: 189-220.
8.
Kim, H., Sun, Y., Yun, S., Kim, B., Hwang, C.N., Lee, S.H. and Nelson, B.J. ( 2004) Mechanical property characterization of the zebrafish embryo chorion. Proceedings of IEEE International Conference of the Engineering in Medicine and Biology Society, pp. 5061-5064.
9.
Kobayashi, K., Kato, K., Saga, M., Yamane, M., Rothman, C.M. and Ogawa, S. ( 1992) Subzonal insemination of a single mouse spermatozoon with a personal computer-controlled micromanipulation system. Journal of Molecular Reproduction and Development, 33: 81-88.
10.
Koch, U.T. and Bushges, A. ( 1990) A high speed recoil-free piezo-drive for cell impalement . Journal of Neuroscience Methods, 35: 261-265.
11.
Komzsik, L. ( 2006) Approximation Techniques for Engineers. CRC Press.
12.
Lacal, J.C., Perona, R. and Feramisco, J. ( 1999) Microinjection. Berlin, Birkhäuser.
13.
Lee, R.C., Despa, F. and Hamann, K.J.2005. Cell Injury: Mechanisms, Responses, and Therapeutics. New York, The New York Academy of Sciences.
14.
Liu, X.Y., Wang, W.H., Gelinas, D., Ciruna, B. and Sun, Y. ( 2007) A fully automated robotic system for microinjection of zebrafish embryos. PLoS ONE, 2: e862.
15.
Lu, Z., Chen, C.Y., Nam, J., Ge, R. and Lin, W. ( 2007) A micromanipulation system with dynamic force-feedback for automatic batch microinjection. Journal of Micromechanics and Microengineering, 17: 314-321.
16.
Matsuoka, H., Shimoda, S., Miwa, Y. and Saito, M. ( 2006) Automatic positioning of a microinjector in mouse ES cells and rice protoplasts. Journal of Biochemistry, 69: 187-192.
17.
Pillarisetti, A., Pekarev, M., Brooks, A. and Desai, J. ( 2007) Evaluating the effect of force feedback in cell injection . IEEE Transactions on Automation Science and Engineering , 4: 322-331.
18.
Roy, J. and Whitcomb, J.J. ( 2002) Adaptive force control of position/velocity controlled robots: theory and experiment. IEEE Transactions on Robotics and Automation, 18: 121- 137.
19.
Samiec, M., and Skrzyszowska, M. (2005) Microsurgical nuclear transfer by intraooplasmic karyoplast injection as an alternative embryo reconstruction method in somatic cloning of pigs and other mammal species; application value of the method and its technical advantages: a review. Czech Journal of Animal Science, 50(6): 235-242.
20.
Seraji, H. and Colbaugh, R.1997. Force tracking in impedance control. The International Journal of Robotics Research, 16: 97-117.
21.
Slotine, J.J. and Li, W. ( 1991) Applied Nonlinear Control. Englewood Cliffs, NJ, Prentice Hall.
22.
Sun, D. and Liu, Y.H. ( 1997) Modeling and impedance control of a two-manipulator system handling a flexible beam. ASME Journal of Dynamic Systems, Measurement, and Control, 119(4): 736-742.
23.
Sun, Y. and Nelson, B.J. ( 2002) Biological cell injection using an autonomous microrobotics system. The International Journal of Robotics Research, 21: 861-868.
24.
Tan, K.K., Ng, D.C. and Xie, Y. ( 2002) Optical intracytoplasmic sperm injection with a piezo micromanipulator. Proceedings of the 4th World Congress on Intelligent Control and Automation, pp. 1120-1123.
25.
Tan, Y., Sun, D., Huang, W. and Cheng, S.H. ( 2008) Mechanical modeling of biological cells in microinjection . IEEE Transactions on Nanobioscience, 7(4): 257-266.
26.
Traoumine, O., Ott, A., Cardoso, O. and Meister, J.J. ( 1999) Microplates: a new tool for manipulation and mechanical perturbation of individual cells. Journal of Biochemical and Biophysical Methods, 39: 47-62.
27.
Wang et al. (2007)
28.
Wejinya, U.C., Shen, Y., Xi, N. and Salem, F. ( 2006) Force measurement of embryonic system using in situ PVDF piezoelectric sensor. IEEE International Midwest Symposium on Circuits and Systems, pp. 108-112.
29.
Westerfield, M. ( 1995) The Zebrafish Book: Guide for the Laboratory Use of Zebrafish (Danio rerio). (3rd edn). Eugene, OR, University of Oregon Press.
30.
Xie, Y., Sun, D., Liu, C., and Cheng, S.H. ( 2009a) A force control based cell injection approach in a bio-robotic system. IEEE International Conference on Robotics and Automation, pp. 3443-3448.
31.
Xie, Y., Sun, D., Liu, C., and Cheng, S.H. ( 2009b) Penetration force measurement and control in robotic cell microinjection. Proceedings of the IEEE Conference on Intelligent Robots and Systems, pp. 4701-4706.
32.
Zeng, G. and Hemami, A. ( 1997) An overview of robot force control. Robotica , 15: 473-482.
