Experiments with a teleoperated system for improved bio-micromanipulations

Cell and embryo microinjections, like many other biomanipulation tasks, involve delicate and precise manual control of micropipettes under a microscope. These operations are repeatedly carried out by highly trained personnel, who spend hours peering through the binoculars of the microscope. As a result, the taxing working conditions and the skills of the operators have a significant impact on the results of the operations. To facilitate the training of new operators and to improve the consistency and efficiency rates of microinjections, we have developed a teleoperated system that demonstrated remarkable improvements in performance and skill acquisition levels during blastocyst microinjection tasks. It combined the advantages of easy, controlled and accurate teleoperation with a more ergonomic work environment, resulting in outstanding reduction in operator training period and amateur performances comparable to those of highly trained operators. This new system, which is fully controlled from a remote computer using a game joystick, was evaluated by comparing teleoperated blastocyst microinjections conducted by one expert and two amateurs. Further, these results were compared to those from expert microinjections conducted on a conventional system. The experiments demonstrated fast learning on the new system and high microinjection success rates (around 90%) for all operators after only three microinjection sessions. Microinjection quality on the new teleoperated system also proved to be high. This was assessed by having the embryos develop to term and computing the birth rates. Higher birth rates (up to twice as high) were observed for embryos injected on the novel system than for those injected on the traditional system. These results prove that the incorporation of robotics into biomanipulation improves the efficiency of the operations, and of the operator, and it eliminates the need for extensive training of microinjection personnel.

[1]  Garth H Ballantyne,et al.  The da Vinci telerobotic surgical system: the virtual operative field and telepresence surgery. , 2003, The Surgical clinics of North America.

[2]  S Ogawa,et al.  Subzonal insemination of a single mouse spermatozoon with a personal computer‐controlled micromanipulation system , 1992, Molecular reproduction and development.

[3]  N. Kashiwazaki,et al.  Personal computer-controlled microsurgery of fertilized eggs and early embryos. , 1986, Theriogenology.

[4]  Louis B. Rosenberg,et al.  Virtual fixtures: Perceptual tools for telerobotic manipulation , 1993, Proceedings of IEEE Virtual Reality Annual International Symposium.

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

[6]  Russell H. Taylor,et al.  Preliminary experiments in robot/human cooperative microinjection , 2003, Proceedings 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453).

[7]  K.K. Tan,et al.  Computer controlled piezo micromanipulation system for biomedical applications , 2001 .

[8]  Edward Grant,et al.  From teleoperated to automatic blastocyst microinjections: Designing a new system from expert-controlled operations , 2008, 2008 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[9]  R Yanagimachi,et al.  Intracytoplasmic sperm injection in the mouse. , 1995, Biology of reproduction.

[10]  M. Washizu,et al.  Handling of biological cells using fluid integrated circuit , 1988, Conference Record of the 1988 IEEE Industry Applications Society Annual Meeting.

[11]  Qiang Ji,et al.  Cell detection and tracking for micromanipulation vision system of cell-operation robot , 2000, Smc 2000 conference proceedings. 2000 ieee international conference on systems, man and cybernetics. 'cybernetics evolving to systems, humans, organizations, and their complex interactions' (cat. no.0.

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

[13]  Ève Coste-Manière,et al.  Haptically augmented teleoperation , 2000, Proceedings 2001 ICRA. IEEE International Conference on Robotics and Automation (Cat. No.01CH37164).

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

[15]  Paolo Dario,et al.  Control of a Teleoperated Nanomanipulator with Time Delay under Direct Vision Feedback , 2007, Proceedings 2007 IEEE International Conference on Robotics and Automation.

[16]  Nikolai Dechev,et al.  Development of a five degree-of-freedom biomanipulator for autonomous single cell electroporation , 2007, 2007 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[17]  Wei Zhao,et al.  A micro visual servo system for biological cell manipulation: overview and new developments , 2002, 7th International Conference on Control, Automation, Robotics and Vision, 2002. ICARCV 2002..

[18]  Edward Grant,et al.  Blastocyst Microinjection Automation , 2009, IEEE Transactions on Information Technology in Biomedicine.

[19]  Jean-Christophe Olivo-Marin,et al.  Active contours for the movement and motility analysis of biological objects , 2000, Proceedings 2000 International Conference on Image Processing (Cat. No.00CH37101).

[20]  Chang-Jin Kim,et al.  Pneumatically driven microcage for micro-objects in biological liquid , 1999, Technical Digest. IEEE International MEMS 99 Conference. Twelfth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.99CH36291).

[21]  Sergej Fatikow,et al.  Micro-force sensing in a micro-robotic system , 2001, Proceedings 2001 ICRA. IEEE International Conference on Robotics and Automation (Cat. No.01CH37164).

[22]  Fumihito Arai,et al.  Bio-micromanipulation (new direction for operation improvement) , 1997, Proceedings of the 1997 IEEE/RSJ International Conference on Intelligent Robot and Systems. Innovative Robotics for Real-World Applications. IROS '97.

[23]  Fumihito Arai,et al.  Single cell trap on a chip using in-situ microfabrication with photo-crosslinkable resin and thermal gelation , 2004, IEEE International Conference on Robotics and Automation, 2004. Proceedings. ICRA '04. 2004.

[24]  Vicente Parra-Vega,et al.  Haptic Teleoperated Robotic System for an Effective Obstacle Avoidance , 2009, 2009 Second International Conferences on Advances in Computer-Human Interactions.

[25]  M. Capecchi,et al.  Targeted gene replacement. , 1994, Scientific American.

[26]  A. Ashkin,et al.  Optical trapping and manipulation of single cells using infrared laser beams , 1987, Nature.

[27]  Russell H. Taylor,et al.  Simple Biomanipulation Tasks with 'Steady Hand' Cooperative Manipulator , 2003, MICCAI.

[28]  R. Petters,et al.  Transgenic animals as models for human disease , 2004, Transgenic Research.

[29]  Darwin G. Caldwell,et al.  Interface Design for MicroBiomanipulation and Teleoperation , 2009, 2009 Second International Conferences on Advances in Computer-Human Interactions.

[30]  J. Vienken,et al.  Rotation of cells in an alternating electric field theory and experimental proof , 2005, The Journal of Membrane Biology.

[31]  Byungkyu Kim,et al.  Mechanical force response of single living cells using a microrobotic system , 2004, IEEE International Conference on Robotics and Automation, 2004. Proceedings. ICRA '04. 2004.