A high-precision robot-aided single-cell biopsy system

In this paper, we present a precise robot-aided single-cell surgery system to perform single-cell biopsy for cells <25 μm in diameter. A microfluidic chip is designed to arrange upto 100 individual cells in an array. A micropipette mounted onto a 3-DOF micromanipulator and a computer mouse-operated high-precision XY stage is developed to perform high-precision and high-throughput single-cell biopsy. The system is evaluated experimentally by extracting two organelles from adherent cells patterned in a microfluidic chip. The fluorescent-labeled nucleus and mitochondria of human foreskin fibroblast cells are biopsied to demonstrate the capability of the proposed system. The survival rate of the semi-automated biopsy is 73% and 45% for mitochondrial and nucleus biopsies, respectively.

[1]  Mingzhu Sun,et al.  Batch-operation process of nuclear transplantation based on global field of view , 2011, Proceedings of the 30th Chinese Control Conference.

[2]  Dong Sun,et al.  Single Cell Transfection through Precise Microinjection with Quantitatively Controlled Injection Volumes , 2016, Scientific Reports.

[3]  Darwin G. Caldwell,et al.  A Fully Automated System for Adherent Cells Microinjection , 2014, IEEE Journal of Biomedical and Health Informatics.

[4]  Yong Wang,et al.  Automated Translational and Rotational Control of Biological Cells With a Robot-Aided Optical Tweezers Manipulation System , 2016, IEEE Transactions on Automation Science and Engineering.

[5]  Tamio Tanikawa,et al.  Fluorescent monitoring using microfluidics chip and development of syringe pump for automation of enucleation to automate cloning , 2009, 2009 IEEE International Conference on Robotics and Automation.

[6]  D. Kaufman,et al.  Multilineage Differentiation from Human Embryonic Stem Cell Lines , 2001, Stem cells.

[7]  Katsumasa Fujita,et al.  Optical trapping and surgery of living yeast cells using a single laser. , 2008, The Review of scientific instruments.

[8]  Nader Pourmand,et al.  Compartmental genomics in living cells revealed by single-cell nanobiopsy. , 2014, ACS nano.

[9]  Fumihito Arai,et al.  On-Chip Enucleation of Bovine Oocytes using Microrobot-Assisted Flow-Speed Control , 2013, Micromachines.

[10]  Xin Zhao,et al.  Automatic somatic cell operating process for nuclear transplantation , 2012, 2012 7th IEEE International Conference on Nano/Micro Engineered and Molecular Systems (NEMS).

[11]  Maurizio Zuccotti,et al.  Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei , 1998, Nature.

[12]  Mingzhu Sun,et al.  Robotic enuleation for oocytes , 2014, The 9th IEEE International Conference on Nano/Micro Engineered and Molecular Systems (NEMS).

[13]  Tamio Tanikawa,et al.  Automated Cell-Cutting for Cell Cloning , 2010 .

[14]  T. Laurent,et al.  Isopycnic Separation of Cells and Cell Organelles by Centrifugation in Modified Colloidal Silica Gradients , 1977 .

[15]  I. Wilmut,et al.  Sheep cloned by nuclear transfer from a cultured cell line , 1996, Nature.

[16]  Yu Sun,et al.  A system for high-speed microinjection of adherent cells. , 2008, The Review of scientific instruments.

[17]  Li Li,et al.  A High-Throughput Automated Microinjection System for Human Cells With Small Size , 2016, IEEE/ASME Transactions on Mechatronics.