A Survey of Force-Assisted Robotic Cell Microinjection Technologies

Cell injection plays an important role in genetics, transgenics, molecular biology, drug discovery, reproductive study, and other biomedical fields. Compared with manual cell microinjection and robotic cell microinjection with sole position feedback, force-assisted robotic cell microinjection can improve the success rate and survival rate of cell injection. In this paper, the state-of-the-art research on microinjection of both adherent cells and suspended cells with microforce sensing techniques is reviewed. The significance of force sensors in the robotic cell injection system is also discussed. Five types of prevalent force sensing methods and their applications in cell microinjection are reviewed. The challenges and promising solutions in automating the cell microinjection process are addressed. Note to Practitioners—Microinjection process is a complex task to perform. As the advance progress of high-performance microforce sensors, force-assisted robotic cell injection has been a hot topic in recent years. This paper presents the state-of-the-art survey of recent developments on microforce sensing for robotic cell microinjection to address the research challenges. Based on microforce sensing and control, microinjection of both adherent and suspended cells can benefit from the force-assisted robotic cell injection process. The main challenges and promising solutions in terms of micromanipulator design, injection control design, cell holder design, penetration scheme design, injecting pipette maintenance, injection volume, cost reduction, and microforce sensor calibration issues have been discussed. The related research trends are summarized.

[1]  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.

[2]  Peter C. Y. Chen,et al.  Force Sensing and Control in Micromanipulation , 2006, IEEE Transactions on Systems, Man, and Cybernetics, Part C (Applications and Reviews).

[3]  Mehdi Ammi,et al.  Biological cell injection visual and haptic interface , 2006, Adv. Robotics.

[4]  Dong Sun,et al.  Force Sensing and Control in Robot-Assisted Suspended Cell Injection System , 2012 .

[5]  Yu Sun,et al.  Microfabricated glass devices for rapid single cell immobilization in mouse zygote microinjection , 2009, Biomedical microdevices.

[6]  K. Chiam,et al.  A three-dimensional random network model of the cytoskeleton and its role in mechanotransduction and nucleus deformation , 2012, Biomechanics and modeling in mechanobiology.

[7]  O. Sahin,et al.  Integrated optical diffractive micrograting-based injection force sensor , 2003, TRANSDUCERS '03. 12th International Conference on Solid-State Sensors, Actuators and Microsystems. Digest of Technical Papers (Cat. No.03TH8664).

[8]  Dong Sun,et al.  A Force Control Approach to a Robot-assisted Cell Microinjection System , 2010, Int. J. Robotics Res..

[9]  Xinyu Liu,et al.  An Automated Force-Controlled Robotic Micromanipulation System for Mechanotransduction Studies of Drosophila Larvae , 2016, IEEE Transactions on Automation Science and Engineering.

[10]  Jakob Schelten,et al.  Piezoresistive sensors on AFM cantilevers with atomic resolution , 1998 .

[11]  Gloria J. Wiens,et al.  A Mechanism Approach for Enhancing the Dynamic Range and Linearity of MEMS Optical Force Sensing , 2011 .

[12]  O. Solgaard,et al.  Microoptical characterization of piezoelectric vibratory microinjections in drosophila embryos for genome-wide RNAi screen , 2006, Journal of Microelectromechanical Systems.

[13]  Qingsong Xu,et al.  An overview of micro-force sensing techniques , 2015 .

[14]  D. Ingber Tensegrity: the architectural basis of cellular mechanotransduction. , 1997, Annual review of physiology.

[15]  W. Walther,et al.  Viral vectors for gene transfer: a review of their use in the treatment of human diseases. , 2000, Drugs.

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

[17]  김병규,et al.  Cellular Force Measurement for Force Reflected Biomanipulation , 2004 .

[18]  N. Amer,et al.  Novel optical approach to atomic force microscopy , 1988 .

[19]  Wenlin Chen,et al.  Robotic cell injection force control based on static PVDF sensor and Fuzzy-PID control method , 2013 .

[20]  Qingsong Xu,et al.  Design, Fabrication, and Testing of an MEMS Microgripper With Dual-Axis Force Sensor , 2015, IEEE Sensors Journal.

[21]  Xinyu Liu,et al.  Vision-based cellular force measurement using an elastic microfabricated device , 2006, 2006 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[22]  Frank Jülicher,et al.  Active behavior of the Cytoskeleton , 2007 .

[23]  Mohammad R. K. Mofrad,et al.  On the Significance of Microtubule Flexural Behavior in Cytoskeletal Mechanics , 2011, PloS one.

[24]  Bradley J. Nelson,et al.  Vision-based force measurement , 2004, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[25]  Frederic Fol Leymarie,et al.  Tracking Deformable Objects in the Plane Using an Active Contour Model , 1993, IEEE Trans. Pattern Anal. Mach. Intell..

[26]  Johana Kuncova Calibration of a capillary pressure microinjection and its implementation within a micromanipulator , 2002 .

[27]  Yantao Shen,et al.  Integrated sensing for ionic polymer–metal composite actuators using PVDF thin films , 2007 .

[28]  Kristin Decker,et al.  Fundamentals Of Light Microscopy And Electronic Imaging , 2016 .

[29]  Dean Ho,et al.  Nanofountain-probe-based high-resolution patterning and single-cell injection of functionalized nanodiamonds. , 2009, Small.

[30]  I. Kola,et al.  Fertilization of human oocytes by microinjection of a single spermatozoon under the zona pellucida. , 1987, Fertility and sterility.

[31]  Bijan Shirinzadeh,et al.  Vision-based force measurement using neural networks for biological cell microinjection. , 2014, Journal of biomechanics.

[32]  Bradley J. Nelson,et al.  A bulk microfabricated multi-axis capacitive cellular force sensor using transverse comb drives , 2002 .

[33]  Qingsong Xu,et al.  Design and development of a piezo-driven microinjection system with force feedback , 2017, Adv. Robotics.

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

[35]  Yu Sun,et al.  Nanonewton force-controlled manipulation of biological cells using a monolithic MEMS microgripper with two-axis force feedback , 2008 .

[36]  Sung-Yong Cho,et al.  Vision-guided micromanipulation system for biomedical application , 2004, SPIE Optics East.

[37]  Qingsong Xu,et al.  Micromachines for Biological Micromanipulation , 2018 .

[38]  R. W. Bernstein,et al.  Micromachined silicon force sensor based on diffractive optical encoders for characterization of microinjection , 2004 .

[39]  Assen Shulev,et al.  All-silicon microforce sensor for bio applications , 2013, Microtechnologies for the New Millennium.

[40]  Imad H. Elhajj,et al.  A 2-D PVDF force sensing system for micro-manipulation and micro-assembly , 2002, Proceedings 2002 IEEE International Conference on Robotics and Automation (Cat. No.02CH37292).

[41]  Edward Grant,et al.  A Review of Automated Microinjection Systems for Single Cells in the Embryogenesis Stage , 2016, IEEE/ASME Transactions on Mechatronics.

[42]  B. Nelson,et al.  A Six-Axis MEMS Force–Torque Sensor With Micro-Newton and Nano-Newtonmeter Resolution , 2009, Journal of Microelectromechanical Systems.

[43]  J. Bereiter-Hahn,et al.  Quantitation of the volume of liquid injected into cells by means of pressure. , 1989, Experimental cell research.

[44]  Robert Barrett,et al.  Atomic force microscopy using a piezoresistive cantilever , 1991, TRANSDUCERS '91: 1991 International Conference on Solid-State Sensors and Actuators. Digest of Technical Papers.

[45]  Tatsuo Arai,et al.  Development of a micro-manipulation system having a two-fingered micro-hand , 1999, IEEE Trans. Robotics Autom..

[46]  Ben Horan,et al.  Haptic Microrobotic Cell Injection System , 2014, IEEE Systems Journal.

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

[48]  Taisuke Masuda,et al.  Selective and rapid cell injection of fluorescence sensor encapsulated in liposome using optical control of zeta potential and local mechanical stimulus by optical tweezers , 2014, 2014 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[49]  Stéphane Régnier,et al.  A planar structure sensitive to out-of-plane forces for the force-controlled injection of suspended and adherent cells , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[50]  T. Ghosh,et al.  Iontophoresis and electroporation: comparisons and contrasts. , 1999, International journal of pharmaceutics.

[51]  Dong Sun,et al.  Mechanical modeling of biological cells in microinjection. , 2008, IEEE transactions on nanobioscience.

[52]  U.C. Wejinya,et al.  Closed-loop optimal control-enabled piezoelectric microforce sensors , 2006, IEEE/ASME Transactions on Mechatronics.

[53]  John F. Canny,et al.  A Computational Approach to Edge Detection , 1986, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[54]  T. Tsuji,et al.  The development of an ova holding device made of microporous glass plate for genetic engineering , 1998, Proceedings of the 20th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Vol.20 Biomedical Engineering Towards the Year 2000 and Beyond (Cat. No.98CH36286).

[55]  Yu Xie,et al.  Penetration force measurement and control in robotic cell microinjection , 2009, 2009 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[56]  S T Quek,et al.  Mechanical models for living cells--a review. , 2006, Journal of biomechanics.

[57]  Pasi Kallio,et al.  Multi-purpose impedance-based measurement system to automate microinjection of adherent cells , 2005, 2005 International Symposium on Computational Intelligence in Robotics and Automation.

[58]  Samir Mitragotri,et al.  An experimental and theoretical analysis of ultrasound-induced permeabilization of cell membranes. , 2003, Biophysical journal.

[59]  Chee Peng Lim,et al.  Formulation and Simulation of a 3D Mechanical Model of Embryos for Microinjection , 2013, 2013 IEEE International Conference on Systems, Man, and Cybernetics.

[60]  Bradley J. Nelson,et al.  Mems for Cellular Force Measurements and Molecular Detection , 2004, Int. J. Inf. Acquis..

[61]  Mehdi Ammi,et al.  Realistic Visual and Haptic Rendering for Biological-Cell Injection , 2005, Proceedings of the 2005 IEEE International Conference on Robotics and Automation.

[62]  R. Burghardt,et al.  Production of Nuclear Transfer Horse Embryos by Piezo-Driven Injection of Somatic Cell Nuclei and Activation with Stallion Sperm Cytosolic Extract1 , 2002, Biology of reproduction.

[63]  H. Fujiwara,et al.  A new assisted hatching technique using a piezo-micromanipulator. , 1998, Fertility and sterility.

[64]  Yang Chongjun,et al.  Design of a microforce sensor based on fixed-simply supported beam: Towards realtime cell microinjection , 2015, 2015 IEEE International Conference on Cyber Technology in Automation, Control, and Intelligent Systems (CYBER).

[65]  Oliver Brock,et al.  NanoNewton Force Sensing and Control in Microrobotic Cell Manipulation , 2009 .

[66]  Qingsong Xu Design and Implementation of Large-Range Compliant Micropositioning Systems , 2016 .

[67]  Jaydev P. Desai,et al.  Force feedback interface for cell injection , 2005, First Joint Eurohaptics Conference and Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems. World Haptics Conference.

[68]  J. Uitto,et al.  The gene gun: current applications in cutaneous gene therapy , 2000, International journal of dermatology.

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

[70]  Toshiro Higuchi,et al.  A micropositioning device for precision automatic assembly using impact force of piezoelectric elements , 1995, Proceedings of 1995 IEEE International Conference on Robotics and Automation.

[71]  Yu Xie,et al.  Force Sensing and Manipulation Strategy in Robot-Assisted Microinjection on Zebrafish Embryos , 2011, IEEE/ASME Transactions on Mechatronics.

[72]  Qingsong Xu,et al.  Design and Precision Position/Force Control of a Piezo-Driven Microinjection System , 2017, IEEE/ASME Transactions on Mechatronics.

[73]  E. Piat,et al.  Experimental measurement of human oocyte mechanical properties on a micro and nanoforce sensing platform based on magnetic springs , 2014 .

[74]  A. Shulev,et al.  Force sensor for cell injection and characterization , 2012, 2012 International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO).

[75]  Bradley J. Nelson,et al.  Biological Cell Injection Using an Autonomous MicroRobotic System , 2002, Int. J. Robotics Res..

[76]  Bradley J. Nelson,et al.  Three-axis micro-force sensor with sub-micro-Newton measurement uncertainty and tunable force range , 2010 .

[77]  Shigeo Wada,et al.  Proposed Spring Network Cell Model Based on a Minimum Energy Concept , 2010, Annals of Biomedical Engineering.

[78]  Hideaki Matsuoka,et al.  High throughput easy microinjection with a single-cell manipulation supporting robot. , 2005, Journal of biotechnology.

[79]  Sehyun Shin,et al.  Advances in the measurement of red blood cell deformability: A brief review , 2015 .

[80]  Mehdi Ammi,et al.  Evaluation of 3D Pseudo-Haptic Rendering using Vision for Cell Micromanipulation , 2006, 2006 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[81]  R. Wall,et al.  Pronuclear microinjection. , 2001, Cloning and stem cells.

[82]  D Marr,et al.  Theory of edge detection , 1979, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[83]  Neville Hogan,et al.  Impedance Control: An Approach to Manipulation: Part I—Theory , 1985 .

[84]  Jaydev P. Desai,et al.  Evaluating the Effect of Force Feedback in Cell Injection , 2007, IEEE Transactions on Automation Science and Engineering.

[85]  Olav Solgaard,et al.  Automated MEMS-based Drosophila embryo injection system for high-throughput RNAi screens. , 2006, Lab on a chip.

[86]  Shusheng Bi,et al.  Automatic micromanipulating system for biological applications with visual servo control , 2001 .

[87]  Uchechukwu C. Wejinya,et al.  Force Measurement of Embryonic System Using In Situ PVDF Piezoelectric Sensor , 2006, 2006 49th IEEE International Midwest Symposium on Circuits and Systems.

[88]  Zhang Yi,et al.  Vision-Servo System for Automated Cell Injection , 2009, IEEE Transactions on Industrial Electronics.

[89]  Yoshiyuki Miwa,et al.  Automatic positioning of a microinjector in mouse ES cells and rice protoplasts. , 2006, Bioelectrochemistry.

[90]  Demetri Terzopoulos,et al.  Snakes: Active contour models , 2004, International Journal of Computer Vision.

[91]  Michael W. Berns,et al.  Laser trapping in cell biology , 1990 .

[92]  Michaël Gauthier,et al.  Capillary Force Disturbances on a Partially Submerged Cylindrical Micromanipulator , 2007, IEEE Transactions on Robotics.

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

[94]  Pasi Kallio,et al.  Capillary Pressure Microinjection of Living Adherent Cells: Challenges in Automation , 2006 .

[95]  Curt D Sigmund,et al.  Efficiency of chimeraplast gene targeting by direct nuclear injection using a GFP recovery assay. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[96]  Jungsik Kim,et al.  A Haptic Interaction Method Using Visual Information and Physically Based Modeling , 2010, IEEE/ASME Transactions on Mechatronics.

[97]  Anne Balck,et al.  Cell Manipulation System Based on a Self-Calibrating Silicon Micro Force Sensor Providing Capillary Status Monitoring , 2012, IEEE Sensors Journal.

[98]  N. Xi,et al.  Novel micro gripping, probing, and sensing devices for single-cell surgery , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[99]  Dong Sun,et al.  Characterizing Mechanical Properties of Biological Cells by Microinjection , 2010, IEEE Transactions on NanoBioscience.

[100]  H. Craighead,et al.  Microfabricated cantilevers for measurement of subcellular and molecular forces , 1998, IEEE Transactions on Biomedical Engineering.

[101]  Brian A. Aguado,et al.  Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. , 2012, Tissue engineering. Part A.

[102]  Xi Wenming,et al.  Bio-manipulation probe integration with micro-force sensor , 2008, 2008 3rd IEEE International Conference on Nano/Micro Engineered and Molecular Systems.

[103]  Hamid Ladjal,et al.  Biomechanical Modeling for Assisted Biological Cell Injection , 2019 .

[104]  Jungsik Kim,et al.  Haptic Feedback Based on Physically Based Modeling for Cellular Manipulation Systems , 2008, EuroHaptics.

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

[106]  Qingsong Xu,et al.  Design of a PVDF-MFC Force Sensor for Robot-Assisted Single Cell Microinjection , 2017, IEEE Sensors Journal.

[107]  K. Hasenstein,et al.  Microinjection--a tool to study gravitropism. , 2003, Advances in space research : the official journal of the Committee on Space Research.

[108]  Tomaso Zambelli,et al.  FluidFM: combining atomic force microscopy and nanofluidics in a universal liquid delivery system for single cell applications and beyond. , 2009, Nano letters.

[109]  Yu Sun,et al.  Mechanical property characterization of the zebrafish embryo chorion , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[110]  Z. Nagy,et al.  Intracytoplasmic sperm injection in the mouse. , 1995, Human reproduction.

[111]  Qingsong Xu,et al.  Advanced Control of Piezoelectric Micro-/Nano-Positioning Systems , 2015 .

[112]  Marie-Pierre Rols,et al.  Electropermeabilization, a physical method for the delivery of therapeutic molecules into cells. , 2006, Biochimica et biophysica acta.

[113]  Qingsong Xu,et al.  Design and Testing of a Flexure-Based Constant-Force Stage for Biological Cell Micromanipulation , 2018, IEEE Transactions on Automation Science and Engineering.

[114]  Yu Sun,et al.  MEMS capacitive force sensors for cellular and flight biomechanics , 2007, Biomedical materials.

[115]  Mingzhu Sun,et al.  Size-Adjustable Microdroplets Generation Based on Microinjection , 2017, Micromachines.