Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content
SpringerLink
Log in

A Thermo-electromagnetically Actuated Microrobot for the Targeted Transport of Therapeutic Agents

  • Regular Papers
  • Robot and Applications
  • Published:
International Journal of Control, Automation and Systems Aims and scope Submit manuscript

Abstract

This work proposes the targeted transport of therapeutic agents using a thermo-electromagnetically actuated microrobot. This microrobot is fabricated via UV polymerization using 2D lithography and is composed of an electromagnetically actuated layer (polyethyleneglycol diacrylate dispersed with iron(II,III) oxide and a thermo-responsive layer (N-isopropylacrylamide). The microrobot can self-fold, driven by temperature changes, and can be steered using an electromagnetic actuation (EMA) system that provides external magnetic fields. In particular, during the EMA, pulling and rolling motions are applied to the unfolded and folded shapes, respectively, of the microrobot. As fundamental tests, the microrobot was characterized in terms of its magnetization curve, swelling properties, travel velocity, and shape changing behavior. In addition, typical polystyrene bead manipulations such as trapping, delivery, and release were performed using the microrobot. Finally, we performed an in vitro test for tumor therapy, in which the robot demonstrated the ability to trap, deliver, and release an anti-cancer drug (docetaxel) encapsulated in microbeads of approximately 300 mm in diameter with an appropriate drug concentration against a mouse mammary tumor cell line (4T1). The outcomes of this research suggest that our thermo-electromagnetically actuated microrobot is suitable for use in biomedical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. B. J. Nelson, I. K. Kaliakatsos, and J. J. Abbott, “Microrobots for minimally invasive medicine,” Annual Review of Biomedical Engineering, vol. 12, pp. 55–85, 2010. [click]

    Article  Google Scholar 

  2. K. E. Peyer, L. Zhang, and B. J. Nelson, “Bio-inspired magnetic swimming microrobots for biomedical applications,” Nanoscale, vol. 5, no. 4, pp. 1259–1272, 2013. [click]

    Article  Google Scholar 

  3. M. Sitti, H. Ceylan, H. Wenqi, J. Giltinan, M. Turan, S. Yim, and E. Diller, “Biomedical applications of untethered mobile milli/microrobots,” Proceedings of the IEEE, vol. 103, no. 2, pp. 205–224, 2015. [click]

    Article  Google Scholar 

  4. J. D. Keuning, J. de Vriesy, L. Abelmanny, and S. Misra, “Image-based magnetic control of paramagnetic microparticles in water,” Proc. of IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS), pp. 421–426, 2011.

    Google Scholar 

  5. H. Choi, K. Cha, S. Jeong, J. Park, and S. Park, “3-D locomotive and drilling microrobot using novel stationary EMA system,” IEEE/ASME Transactions on Mechatronics, vol. 18, no. 3, pp. 1221–1225, 2013. [click]

    Article  Google Scholar 

  6. M. T. Hou, H. M. Shen, G. L. Jiang, C. N. Lu, I. J. Hsu, and J. A. Yeh, “A rolling locomotion method for untethered magnetic microrobots,” Applied Physics Letters, vol. 96, no. 2, pp. 024102, 2010. [click]

    Article  Google Scholar 

  7. E. Diller and M. Sitti, “Three-dimensional programmable assembly by untethered magnetic robotic micro-grippers,” Advanced Functional Materials, vol. 24, no. 28, pp. 4397–4404, 2014. [click]

    Article  Google Scholar 

  8. A. W. Mahoney, J. C. Sarrazin, E. Bamberg, and J. J. Abbott, “Velocity control with gravity compensation for magnetic helical microswimmers,” Advanced Robotics, vol. 25, no. 8, pp. 1007–1028, 2011. [click]

    Article  Google Scholar 

  9. P. Mandal, V. Chopra, and A. Ghosh, “Independent positioning of magnetic nanomotors,” ACS Nano, vol. 9, no. 5, pp. 4717–4725, 2015.

    Article  Google Scholar 

  10. I. S. M. Khalil, H. C. Dijkslag, L. Abelmann, and S. Misra, “MagnetoSperm: a microrobot that navigates using weak magnetic fields,” Applied Physics Letters, vol. 104, no. 22, pp. 223701, 2014. [click]

    Article  Google Scholar 

  11. K. Youakim, M. Ehab, O. Hatem, S. Misra, and I. S. M. Khalil, “Paramagnetic microparticles sliding on a surface: Characterization and closed-loop motion control,” Proc. of IEEE International Conference on Robotics and Automation (ICRA), pp. 4068–4073, 2015. [click]

    Google Scholar 

  12. C. Pawashe, S. Floyd, and M. Sitti, “Modeling and experimental characterization of an untethered magnetic microrobot,” The International Journal of Robotics Research, vol. 28, no. 8, pp. 1077–1094, 2009.

    Article  Google Scholar 

  13. J. Li, T. Li, T. Xu, M. Kiristi, W. Liu, Z. Wu, and J. Wang, “Magneto-acoustic hybrid nanomotor,” Nano Letters, vol. 15, no. 7, pp. 4814–4821, 2015. [click]

    Article  Google Scholar 

  14. J. C. Breger, C. Yoon, R. Xiao, H. R. Kwag, M. O. Wang, J. P. Fisher, T. D. Nguyen, and D. H. Gracias, “Self-folding thermo-magnetically responsive soft microgrippers,” ACS Appl Mater Interfaces, vol. 7, no. 5, pp. 3398–3405, 2015. [click]

    Article  Google Scholar 

  15. E. Diller, N. Zhang, and M. Sitti, “Modular micro-robotic assembly through magnetic actuation and thermal bonding,” Journal of Micro-Bio Robotics, vol. 8, no. 3–4, pp. 121–131, 2013.

    Article  Google Scholar 

  16. S. Fusco, M. S. Sakar, S. Kennedy, C. Peters, R. Bottani, F. Starsich, A. Mao, G. A. Sotiriou, S. Pane, S. E. Pratsinis, D. Mooney, and B. J. Nelson, “An integrated microrobotic platform for on-demand, targeted therapeutic interventions,” Advanced Materials, vol. 26, no. 6, pp. 952–957, 2014.

    Article  Google Scholar 

  17. J.-C. Kuo, H.-W. Huang, S.-W. Tung, and Y.-J. Yang, “A hydrogel-based intravascular microgripper manipulated using magnetic fields,” Sensors and Actuators A: Physical, vol. 211, pp. 121–130, 2014.

    Article  Google Scholar 

  18. S. Miyashita, S. Guitron, M. Ludersdorfer, C. R. Sung, and D. Rus, “An untethered miniature origami robot that selffolds, walks, swims, and degrades,” Proc. of IEEE International Conference on Robotics and Automation (ICRA), pp. 1490–1496, 2015. [click]

    Google Scholar 

  19. S. N. Tabatabaei, J. Lapointe, and S. Martel, “Shrinkable hydrogel-based magnetic microrobots for interventions in the vascular network,” Advanced Robotics, vol. 25, no. 8, pp. 1049–1067, 2011. [click]

    Article  Google Scholar 

  20. D. Li, H. Choi, S. Cho, S. Jeong, Z. Jin, C. Lee, S. Y. Ko, J. O. Park, and S. Park, “A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumortargeting therapy,” Biotechnology and Bioengineering, vol. 112, no. 8, pp. 1623–1631, 2015. [click]

    Article  Google Scholar 

  21. V. Magdanz, S. Sanchez, and O. G. Schmidt, “Development of a sperm-flagella driven micro-bio-robot,” Advanced Materials, vol. 25, no. 45, pp. 6581–6588, 2013. [click]

    Article  Google Scholar 

  22. I. S. Khalil, V. Magdanz, S. Sanchez, O. G. Schmidt, and S. Misra, “Wireless magnetic-based closed-loop control of self-propelled microjets,” PLoS One, vol. 9, no. 2, pp. e83053, 2014. [click]

    Article  Google Scholar 

  23. A. A. Solovev, Y. Mei, E. Bermudez Urena, G. Huang, and O. G. Schmidt, “Catalytic microtubular jet engines selfpropelled by accumulated gas bubbles,” Small, vol. 5, no. 14, pp. 1688–1692, 2009.

    Article  Google Scholar 

  24. S. Cho, S. J. Park, S. Y. Ko, J. O. Park, and S. Park, “Development of bacteria-based microrobot using biocompatible poly(ethylene glycol),” Biomed Microdevices, vol. 14, no. 6, pp. 1019–25, 2012.

    Article  Google Scholar 

  25. V. Nerapusri, J. L. Keddie, B. Vincent, and I. A. Bushnak, “Swelling and deswelling of adsorbed microgel monolayers triggered by changes in temperature, pH, and electrolyte concentration,” Langmuir, vol. 22, no. 11, pp. 5036–5041, 2006. [click]

    Article  Google Scholar 

  26. C. Yu, Y. Pan, H. Ma, T. Ma, J. Zhang, Y. Song, M. Y. Kalani, L. Dai, and H. Jiang, “Thermoresponsiveness of integrated ultra-thin silicon with poly (Nisopropylacrylamide) hydrogels,” Macromolecular rapid communications, vol. 32, no. 11, pp. 820–824, 2011.

    Article  Google Scholar 

  27. G. Go, H. Choi, S. Jeong, S. Y. Ko, J. Park, and S. Park, “Selective microrobot control using a thermally responsive microclamper for microparticle manipulation,” Smart Materials and Structures, vol. 25, no. 3, pp. 035004, 2016.

    Article  Google Scholar 

  28. H. Choi, J. Choi, G. Jang, J. Park, and S. Park, “Twodimensional actuation of a microrobot with a stationary two-pair coil system,” Smart Materials and Structures, vol. 18, no. 5, pp. 055007, 2009.

    Article  Google Scholar 

  29. S. Jeong, H. Choi, K. Cha, J. Li, J. Park, and S. Park, “Enhanced locomotive and drilling microrobot using precessional and gradient magnetic field,” Sensors and Actuators A: Physical, vol. 171, no. 2, pp. 429–435, 2011. [click]

    Article  Google Scholar 

  30. S. Floyd, C. Pawashe, and M. Sitti, “Two-dimensional contact and noncontact micromanipulation in liquid using an untethered mobile magnetic microrobot,” IEEE Transactions on Robotics, vol. 25, no. 6, pp. 1332–1342, 2009. [click]

    Article  Google Scholar 

  31. U. K. Cheang, F. Meshkati, D. Kim, M. J. Kim, and H. C. Fu, “Minimal geometric requirements for micropropulsion via magnetic rotation,” Physical Review E, vol. 90, no. 3, pp. 033007, 2014. [click]

    Article  Google Scholar 

  32. C. G. Keum, Y.W. Noh, J. S. Baek, J. H. Lim, C. J. Hwang, Y. G. Na, S. C. Shin, and C. W. Cho, “Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid,” International Journal of Nanomedicine, vol. 6, pp. 2225–34, 2011. [click]

    Google Scholar 

  33. M. S. Muthu, S. A. Kulkarni, J. Xiong, and S. S. Feng, “Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells,” International Journal of Pharmaceutics, vol. 421, no. 2, pp. 332–340, 2011.

    Article  Google Scholar 

  34. S. J. Park, S. H. Park, S. Cho, D. M. Kim, Y. Lee, S. Y. Ko, Y. Hong, H. E. Choy, J. J. Min, J. O. Park, and S. Park, “New paradigm for tumor theranostic methodology using bacteria-based microrobot,” Scientific reports, vol. 3, pp. 1–8, 2013.

    Google Scholar 

  35. C.-W. Lo, D. Zhu, and H. Jiang, “An infraredlight responsive graphene-oxide incorporated poly(Nisopropylacrylamide) hydrogel nanocomposite,” Soft Matter, vol. 7, no. 12, pp. 5604–5609, 2011.

    Article  Google Scholar 

  36. N. S. Satarkar and J. Z. Hilt, “Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release,” Journal of Controlled Release, vol. 130, no. 3, pp. 246–251, 2008. [click]

    Article  Google Scholar 

  37. A. W. Mahoney, N. D. Nelson, K. E. Peyer, B. J. Nelson, and J. J. Abbott, “Behavior of rotating magnetic microrobots above the step-out frequency with application to control of multi-microrobot systems,” Applied Physics Letters, vol. 104, no. 14, pp. 144101, 2014. [click]

    Article  Google Scholar 

  38. P. Ginet, K. Montagne, S. Akiyama, A. Rajabpour, A. Taniguchi, T. Fujii, Y. Sakai, B. Kim, D. Fourmy, and S. Volz, “Towards single cell heat shock response by accurate control on thermal confinement with an on-chip microwire electrode,” Lab Chip, vol. 11, no. 8, pp. 1513–1520, 2011. [click]

    Article  Google Scholar 

  39. S. Wang, K. R. Diller, and S. J. Aggarwal, “Kinetics study of endogenous heat shock protein 70 expression,” International Mechanical Engineering Congress and Exposition, vol. 125, no. 6, pp. 794–797, 2003.

    Google Scholar 

  40. H. Liu, F. Sun, D. Guo, B. Fang, and Z. Peng, “Structured output-associated dictionary learning for haptic understanding,” IEEE Transactions on Systems, Man, and Cybernetics: Systems, vol. 47, no. 7, pp. 1564–1574, 2017. [click]

    Article  Google Scholar 

  41. H. Liu, Y. Yu, F. Sun, and J. Gu, “Visual–tactile fusion for object recognition,” IEEE Transactions on Automation Science and Engineering, vol. 14, no. 2, pp. 996–1008, 2017. [click]

    Article  Google Scholar 

  42. H. Liu, D. Guo, and F. Sun, “Object recognition using tactile measurements: kernel sparse coding methods,” IEEE Transactions on Instrumentation and Measurement, vol. 65, no. 3, pp. 656–665, 2016. [click]

    Article  Google Scholar 

  43. H. Maeda, H. Nakamura, and J. Fang, “The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo,” Advanced drug delivery reviews, vol. 65, no. 1, pp. 71–79, 2013. [click]

    Article  Google Scholar 

  44. V. Torchilin, “Tumor delivery of macromolecular drugs based on the EPR effect,” Advanced Drug Delivery Reviews, vol. 63, no. 3, pp. 131–135, 2011. [click]

    Article  Google Scholar 

  45. S. Zheng, Z. Jin, J. Han, S. Cho, V. D. Nguyen, S. Y. Ko, J. Park, and S. Park, “Preparation of HIFU-triggered tumortargeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake,” Colloids and Surfaces B: Biointerfaces, vol. 143, pp. 27–36, 2016. [click]

    Article  Google Scholar 

  46. C. Oerlemans, W. Bult, M. Bos, G. Storm, J. F. Nijsen, and W. E. Hennink, “Polymeric micelles in anticancer therapy: targeting, imaging and triggered release,” Pharmaceutical Research, vol. 27, no. 12, pp. 2569–2589, 2010. [click]

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, Korea

    Gwangjun Go, Van Du Nguyen, Zhen Jin & Jong-Oh Park

  2. Medical Microrobot Center (MRC), Robot Research Initiative (RRI), Chonnam National University, Gwangju, 61186, Korea

    Gwangjun Go & Jong-Oh Park

  3. School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, Korea

    Gwangjun Go & Jong-Oh Park

  4. Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 42988, Korea

    Sukho Park

Authors
  1. Gwangjun Go
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Van Du Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhen Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong-Oh Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sukho Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jong-Oh Park or Sukho Park.

Additional information

Recommended by Associate Editor Huaping Liu under the direction of Editor Fuchun Sun. This work was supported by the Industrial Technology Innovation Program [10060059, Externally Actuatable Nanorobot System for Precise Targeting and Controlled Releasing of Drugs] funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea).

Gwangjun Go received his B.S. (2013) and M.S. (2015) degrees from the Department of Mechanical Engineering at Chonnam National University, Korea. Currently, he is a researcher in the Robot Research Initiative (RRI). His research interests are micro/nanorobots.

Van Du Nguyen received his Master’s degree of Science in Industrial & Systems Engineering from Korea Advanced Institute of Science and Technology (KAIST), Korea in 2009. In 2014, he joined the Robot Research Initiative, School of Mechanical Engineering, Chonnam National University, Korea as a Ph.D. student. His research interests include biomedical micro/nano robots, targeted drug delivery systems.

Jin Zhen received his B.S. (2012) degree from the department of Mechanical Engineering at Yanbian University of Science and Technology (YUST), China. Currently, he is a Ph.D. candidate in Chonnam National University and a researcher in Robot Research Initiative (RRI). His research interests are micro/nanorobots, high focused ultrasound (HIFU), and drug delivery system.

Jong-Oh Park received his B.S. (1978) and M.S. (1981) degrees from the Department of Mechanical Engineering, Korea, and his Ph.D. (1987) in robotics from Stuttgart University, Germany. From 1982 to 1987, he worked as a guest researcher at Fraunhofer-Gesellschaft Institut fur Produktionstechnik und Automatisierung (FhG IPA), Germany. He worked as a principal researcher at Korea Institute of Science and Technology (KIST) from 1987 to 2005 and he was a director of the Microsystem Research Center at KIST from 1999 to 2005. In 2005, he moved to Chonnam National University, where he is now a full professor in the Department of Mechanical System Engineering and a director of the Robot Research Initiative (RRI). His research interests are biomedical microrobots, medical robots, and service robots.

Sukho Park earned his Master’s degree (1995) and Ph.D. (2000) in Mechanical Engineering from Korea Advanced Institute of Science and Technology (KAIST), Korea. From 2000 to 2004, he worked as a senior research engineer at LG Electronics Production Research Center, Korea. From 2004 to 2006, he worked as a senior researcher of Microsystem Research Center in the Korea Institute of Science and Technology. From 2006 to 2016, he worked as a professor of the School of Mechanical Engineering in Chonnam National University and a section head of the robot research initiative (RRI). In 2017, he moved to Daegu Gyeongbuk Institute of Science and Technology (DGIST), where he is now a full professor in Department of Robotics Engineering. His research interests are microactuator/robot and micromanipulation for biomedical instrumental applications.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Go, G., Nguyen, V.D., Jin, Z. et al. A Thermo-electromagnetically Actuated Microrobot for the Targeted Transport of Therapeutic Agents. Int. J. Control Autom. Syst. 16, 1341–1354 (2018). https://doi.org/10.1007/s12555-017-0060-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12555-017-0060-z

Keywords

Search

Navigation