Automated biomanipulation of single cells using magnetic microrobots

Transport of individual cells or chemical payloads on a subcellular scale is an enabling tool for the study of cellular communication, cell migration, and other localized phenomena. We present a magnetically actuated robotic system capable of fully automated manipulation of cells and microbeads. Our strategy uses autofluorescent robotic transporters and fluorescently labeled microbeads to aid tracking and control in optically obstructed environments. We demonstrate automated delivery of microbeads infused with chemicals to specified positions on neurons. This system is compatible with standard upright and inverted light microscopes and is capable of applying forces less than 1 pN for precision positioning tasks.

[1]  Vijay Kumar,et al.  Biosensing and actuation for microbiorobots , 2010, 2010 IEEE International Conference on Robotics and Automation.

[2]  M. C. Stuart,et al.  Emerging applications of stimuli-responsive polymer materials. , 2010, Nature materials.

[3]  Ioannis K. Kaliakatsos,et al.  Microrobots for minimally invasive medicine. , 2010, Annual review of biomedical engineering.

[4]  David H Gracias,et al.  Tetherless thermobiochemically actuated microgrippers , 2009, Proceedings of the National Academy of Sciences.

[5]  J. Voldman Electrical forces for microscale cell manipulation. , 2006, Annual review of biomedical engineering.

[6]  Jake J. Abbott,et al.  Robotics in the Small, Part I: Microbotics , 2007, IEEE Robotics & Automation Magazine.

[7]  Vijay Kumar,et al.  Wireless manipulation of single cells using magnetic microtransporters , 2011, 2011 IEEE International Conference on Robotics and Automation.

[8]  G. Whitesides,et al.  Water-soluble sacrificial layers for surface micromachining. , 2005, Small.

[9]  Hajime Takano,et al.  Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor , 2006, Nature Methods.

[10]  Krzysztof K. Krawczyk,et al.  Magnetic Helical Micromachines: Fabrication, Controlled Swimming, and Cargo Transport , 2012, Advanced materials.

[11]  P. Fischer,et al.  Controlled propulsion of artificial magnetic nanostructured propellers. , 2009, Nano letters.

[12]  Li Zhang,et al.  Artificial bacterial flagella for micromanipulation. , 2010, Lab on a chip.

[13]  K. Neuman,et al.  Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy , 2008, Nature Methods.

[14]  Harvey F. Silverman,et al.  A Class of Algorithms for Fast Digital Image Registration , 1972, IEEE Transactions on Computers.

[15]  Metin Sitti,et al.  Two-Dimensional Contact and Noncontact Micromanipulation in Liquid Using an Untethered Mobile Magnetic Microrobot , 2009, IEEE Transactions on Robotics.

[16]  X. Zhu,et al.  Polymer microspheres for controlled drug release. , 2004, International journal of pharmaceutics.

[17]  I. Lundström,et al.  Microrobots for micrometer-size objects in aqueous media: potential tools for single-cell manipulation. , 2000, Science.

[18]  George J. Pappas,et al.  Single Cell Manipulation using Ferromagnetic Composite Microtransporters , 2010 .

[19]  Ming C. Wu,et al.  Massively parallel manipulation of single cells and microparticles using optical images , 2005, Nature.

[20]  George M. Whitesides,et al.  Composite ferromagnetic photoresist for the fabrication of microelectromechanical systems , 2005 .

[21]  Wenqi Hu,et al.  Hydrogel microrobots actuated by optically generated vapour bubbles. , 2012, Lab on a chip.

[22]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[23]  Bradley J. Nelson,et al.  Modeling and Control of Untethered Biomicrorobots in a Fluidic Environment Using Electromagnetic Fields , 2006, Int. J. Robotics Res..

[24]  David H. Gracias,et al.  Toward a miniaturized mechanical surgeon , 2009 .

[25]  Metin Sitti,et al.  Modeling and Experimental Characterization of an Untethered Magnetic Micro-Robot , 2009, Int. J. Robotics Res..

[26]  Michaël Gauthier,et al.  Modelling of a planar magnetic micropusher for biological cell manipulations , 2007 .

[27]  Dominic R. Frutiger,et al.  Small, Fast, and Under Control: Wireless Resonant Magnetic Micro-agents , 2010, Int. J. Robotics Res..

[28]  Jake J. Abbott,et al.  OctoMag: An Electromagnetic System for 5-DOF Wireless Micromanipulation , 2010, IEEE Transactions on Robotics.

[29]  Cecile O. Mejean,et al.  Cell stimulation with optically manipulated microsources , 2009, Nature Methods.

[30]  Michaël Gauthier,et al.  An electromagnetic micromanipulation system for single-cell manipulation , 2002 .

[31]  Jaydev P Desai,et al.  Engineering approaches to biomanipulation. , 2007, Annual review of biomedical engineering.

[32]  P. Fischer,et al.  Magnetically actuated propulsion at low Reynolds numbers: towards nanoscale control. , 2011, Nanoscale.

[33]  Taisuke Masuda,et al.  On-chip magnetically actuated robot with ultrasonic vibration for single cell manipulations. , 2011, Lab on a chip.