Formal Verification of Robotic Cell Injection systems up to 4-DOF using HOL Light

Cell injection is an approach used for the delivery of small sample substances into a biological cell and is widely used in drug development, gene injection, intracytoplasmic sperm injection and in-vitro fertilization. Robotic cell injection systems provide the automation of the process as opposed to the manual and semi-automated cell injection systems, which require expert operators and involve time consuming processes and also have lower success rates. The automation of the cell injection process is obtained by controlling the orientation and movement of its various components, like injection manipulator, microscope etc., and planning the motion of the injection pipette by controlling the force of the injection. The conventional techniques to analyze the cell injection process include paper-and-pencil proof and computer simulation methods. However, both these techniques suffer from their inherent limitations, such as, proneness to human error for the former and the approximation of the mathematical expressions involved in the numerical algorithms for the latter. Formal methods have the capability to overcome these limitations and can provide an accurate analysis of these cell injection systems. Model checking, i.e., a state-based formal method, has been recently used for analyzing these systems. However, it involves the discretization of the differential equations capturing the continuous dynamics of the system and thus compromises on the completeness of the analysis of these safety-critical systems. In this paper, we propose a higher-order-logic theorem proving (a deductive-reasoning based formal method) based framework for analyzing the dynamical behavior of the robotic cell injection systems upto 4-DOF. The proposed analysis, based on the HOL Light theorem prover, enabled us to identify some discrepancies in the simulation and model checking based analysis of the same robotic cell injection system.

[1]  Davide Bresolin,et al.  Formal verification of robotic surgery tasks by reachability analysis , 2015, Microprocess. Microsystems.

[2]  Mark W. Spong,et al.  Robotica: a Mathematica package for robot analysis , 1994, IEEE Robotics & Automation Magazine.

[3]  John Harrison,et al.  The HOL Light Theory of Euclidean Space , 2012, Journal of Automated Reasoning.

[4]  Hend Dawood,et al.  Theories of Interval Arithmetic: Mathematical Foundations and Applications , 2011 .

[5]  Sebastian Muller Ml For The Working Programmer , 2016 .

[6]  Yunhui Liu,et al.  Modeling and impedance control of a two-manipulator system handling a flexible beam , 1997, Proceedings of International Conference on Robotics and Automation.

[7]  Osman Hasan,et al.  Formal verification of robotic cell injection systems , 2020 .

[8]  Ben Horan,et al.  Large-scale Virtual Reality micro-robotic cell injection training , 2016, 2016 World Automation Congress (WAC).

[9]  Osman Hasan,et al.  Formal Modeling of Robotic Cell Injection Systems in Higher-order Logic (short paper) , 2018, CICM Workshops.

[10]  M. Gordon HOL: A Proof Generating System for Higher-Order Logic , 1988 .

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

[12]  Osman Hasan,et al.  Formal Probabilistic Analysis of a Virtual Fixture Control Algorithm for a Surgical Robot , 2017, VECoS.

[13]  Ben Horan,et al.  Towards large-scale haptic virtual reality training for micro-robotic cell injection , 2016, 2016 5th International Conference on Wireless Networks and Embedded Systems (WECON).

[14]  Antonio J. Durán Guardeño,et al.  Misfortunes of a mathematicians' trio using Computer Algebra Systems: Can we trust? , 2013, ArXiv.

[15]  John Harrison,et al.  Handbook of Practical Logic and Automated Reasoning , 2009 .

[16]  Osman Hasan,et al.  Formal Analysis of Robotic Cell Injection Systems using Theorem Proving , 2017, CyPhy.

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

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

[19]  H. Katayose,et al.  The usefulness of a piezo-micromanipulator in intracytoplasmic sperm injection in humans. , 1999, Human reproduction.

[20]  Andrea Bianco,et al.  Model Checking of Probabalistic and Nondeterministic Systems , 1995, FSTTCS.

[21]  John Harrison,et al.  HOL Light: A Tutorial Introduction , 1996, FMCAD.

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

[23]  Edmund M. Clarke,et al.  Model Checking and the State Explosion Problem , 2011, LASER Summer School.

[24]  Osman Hasan,et al.  Towards Probabilistic Formal Modeling of Robotic Cell Injection Systems , 2017, MARS@ETAPS.

[25]  Peter Kazanzides,et al.  Certifying the safe design of a virtual fixture control algorithm for a surgical robot , 2013, HSCC '13.

[26]  Sofiène Tahar,et al.  Formal Verification Methods , 2015 .

[27]  Haibo Huang,et al.  A Visual Impedance Force Control of A Robotic Cell Injection System , 2006, 2006 IEEE International Conference on Robotics and Biomimetics.