Biomedical Microdevices

, Volume 12, Issue 3, pp 371–379 | Cite as

Internalization and cytotoxicity analysis of silicon-based microparticles in macrophages and embryos

  • Elisabet Fernández-Rosas
  • Rodrigo Gómez
  • Elena Ibañez
  • Lleonard Barrios
  • Marta Duch
  • Jaume Esteve
  • José A. Plaza
  • Carme Nogués


Microchips can be fabricated, using semiconductor technologies, at microscopic level to be introduced into living cells for monitoring of intracellular parameters at a single cell level. As a first step towards intracellular chips development, silicon and polysilicon microparticles of controlled shape and dimensions were fabricated and introduced into human macrophages and mouse embryos by phagocytosis and microinjection, respectively. Microparticles showed to be non-cytotoxic for macrophages and were found to be localized mainly inside early endosomes, in tight association with endosomal membrane, and more rarely in acidic compartments. Embryos with microinjected microparticles developed normally to the blastocyst stage, confirming the non-cytotoxic effect of the particles. In view of these results silicon and polysilicon microparticles can serve as the frame for future intracellular chips development and this technology opens the possibility of real complex devices to be used as sensors or actuators inside living cells.


Silicon Polysilicon Microparticle MEMS Cytotoxicity 



confocal laser scanning microscopy


focus ion beam


IntraCellular Chips


MicroElectroMechanical Systems






polystyrene fluorescent microspheres


polysilicon MP


scanning electron microscope


Silicon MP


transmission electron microscopy

Supplementary material

10544_2009_9393_Fig1_ESM.gif (132 kb)
Fig. S1

Shows a schematic representation of the fabrication process of Si- and pSi-MPs. Video 1 shows a FIB sectioning of a macrophage with an internalized Si-MP. Video 2 presents a xyz reconstruction of consecutive focal planes of a macrophage with an internalized pSi-MP. Video S3 provides the microinjection process of a pSi-MP into the cytoplasm of a mouse one-cell embryo. (GIF 132 kb)

10544_2009_9393_Fig1_ESM.tif (3.6 mb)
High Resolution Image(TIFF 3724 kb)
Video 1

(AVI 2962 kb)

10544_2009_9393_MOESM2_ESM.avi (8.3 mb)
Video 2(AVI 8476 kb)
Video 3

(AVI 2005 kb)


  1. S. Abes, D. Williams, P. Prevot, A. Thierry, M.J. Gait, B. Lebleu, J. Control. Release 110(3), 595 (2006)CrossRefGoogle Scholar
  2. G. Bao, S. Suresh, Nat. Mater. 2(11), 715 (2003)CrossRefGoogle Scholar
  3. J.D. Biggers, L.K. McGinnis, M. Raffin, Biol. Reprod. 63(1), 281 (2000)CrossRefGoogle Scholar
  4. T.P. Burg, M. Godin, S.M. Knudsen, W. Shen, G. Carlson, J.S. Foster, K. Babcock, S.R. Manalis, Nature 446(7139), 1066 (2007)CrossRefGoogle Scholar
  5. J. Choi, Q. Zhang, V. Reipa, N.S. Wang, M.E. Stratmeyer, V.M. Hitchins, P.L. Goering, J. Appl. Toxicol. 29(1), 52 (2009)CrossRefGoogle Scholar
  6. S.E. Cross, Y.S. Jin, J. Rao, J.K. Gimzewski, Nat. Nanotechnol. 2(12), 780 (2007)CrossRefGoogle Scholar
  7. C. de Chastellier, L. Thilo, Cell. Microbiol. 8(2), 242 (2006)CrossRefGoogle Scholar
  8. S. Faraasen, J. Voros, G. Csucs, M. Textor, H.P. Merkle, E. Walter, Pharm. Res. 20(2), 237 (2003)CrossRefGoogle Scholar
  9. C. Foged, B. Brodin, S. Frokjaer, A. Sundblad, Int. J. Pharm. 298(2), 315 (2005)CrossRefGoogle Scholar
  10. J. Fritz, M.K. Baller, H.P. Lang, H. Rothuizen, P. Vettiger, E. Meyer, H.J. Guntherodt, C. Gerber, J.K. Gimzewski, Science 288(5464), 316 (2000)CrossRefGoogle Scholar
  11. A.J. Gomes, A.S. Faustino, A.E.H. Machado, M.E.D. Zaniquelli, T.D. Rigoletto, C.N. Lunardi, L.O. Lunardi, Drug Deliv. 13(6), 447 (2006)CrossRefGoogle Scholar
  12. D.S. Gray, J.L. Tan, J. Voldman, C.S. Chen, Biosens. Bioelectron. 19(12), 1763 (2004)CrossRefGoogle Scholar
  13. J.K. Hsiao, C.P. Tsai, T.H. Chung, Y. Hung, M. Yao, H.M. Liu, C.Y. Mou, C.S. Yang, Y.C. Chen, D.M. Huang, Small 4(9), 1445 (2008)CrossRefGoogle Scholar
  14. K.K. Huynh, E.L. Eskelinen, C.C. Scott, A. Malevanets, P. Saftig, S. Grinstein, EMBO J. 26(2), 313 (2007)CrossRefGoogle Scholar
  15. A.M. Javier, O. Kreft, M. Semmling, S. Kempter, A.G. Skirtach, O.T. Bruns, P. del Pino, M.F. Bedard, J. Raedler, J. Kaes, C. Plank, G.B. Sukhorukov, W.J. Parak, Adv. Mater. 20(22), 4281 (2008)CrossRefGoogle Scholar
  16. P.B. Kang, A.K. Azad, J.B. Torrelles, T.M. Kaufman, A. Beharka, E. Tibesar, L.E. DesJardin, L.S. Schlesinger, J. Exp. Med. 202(7), 987 (2005)CrossRefGoogle Scholar
  17. H. Lee, Y. Liu, D. Ham, R.M. Westervelt, Lab Chip 7(3), 331 (2007)CrossRefGoogle Scholar
  18. J. Lu, M. Liong, J.I. Zink, F. Tamanoi, Small 3(8), 1341 (2007)CrossRefGoogle Scholar
  19. J.S. Mcdowell, R.J. Swanson, M. Maloney, L. Veeck, J. In Vitro Fert. Embryo Transf. 5(3), 144 (1988)CrossRefGoogle Scholar
  20. Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, U. Simon, G. Schmid, W. Brandau, W. Jahnen-Dechent, Small 3, 1941 (2007)CrossRefGoogle Scholar
  21. C.E. Pedraza, L.G. Nikolcheva, M.T. Kaartinen, J.E. Barralet, M.D. McKee, Bone 43(4), 708 (2008)CrossRefGoogle Scholar
  22. S.C.W. Richardson, K.L. Wallom, E.L. Ferguson, S.P.E. Deacon, M.W. Davies, A.J. Powell, R.C. Piper, R. Duncan, J. Control. Release 127(1), 1 (2008)CrossRefGoogle Scholar
  23. G. Shekhawat, S.H. Tark, V.P. Dravid, Science 311(5767), 1592 (2006)CrossRefGoogle Scholar
  24. I. Slowing, B.G. Trewyn, V.S.Y. Lin, J. Am. Chem. Soc. 128(46), 14792 (2006)CrossRefGoogle Scholar
  25. I.I. Slowing, B.G. Trewyn, V.S.Y. Lin, J. Am. Chem. Soc. 129(28), 8845 (2007)CrossRefGoogle Scholar
  26. E. Tasciotti, X.W. Liu, R. Bhavane, K. Plant, A.D. Leonard, B.K. Price, M.M.C. Cheng, P. Decuzzi, J.M. Tour, F. Robertson, M. Ferrari, Nat. Nanotechnol. 3(3), 151 (2008)CrossRefGoogle Scholar
  27. L. Thiele, B. Rothen-Rutishauser, S. Jilek, H. Wunderli-Allenspach, H.P. Merkle, E. Walter, J. Control. Release 76(1–2), 59 (2001)CrossRefGoogle Scholar
  28. L. Thiele, H.P. Merkle, E. Walter, Pharm. Res. 20(2), 221 (2003)CrossRefGoogle Scholar
  29. A.P.F. Trombone, C.L. Silva, L.P. Almeida, R.S. Rosada, K.M. Lima, C. Oliver, M.C. Jamur, A.A. Coelho-Castelo, Genet. Vaccines Ther. 5, 9 (2007)CrossRefGoogle Scholar
  30. H. Vallhov, S. Gabrielsson, M. Stromme, A. Scheynius, A.E. Garcia-Bennett, Nano Lett. 7(12), 3576 (2007)CrossRefGoogle Scholar
  31. N. van der Wel, D. Hava, D. Houben, D. Fluitsma, M. van Zon, J. Pierson, M. Brenner, P.J. Peters, Cell 129(7), 1287 (2007)CrossRefGoogle Scholar
  32. A. Verma, O. Uzun, Y.H. Hu, Y. Hu, H.S. Han, N. Watson, S.L. Chen, D.J. Irvine, F. Stellacci, Nat. Mater. 7(7), 588 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Elisabet Fernández-Rosas
    • 1
    • 2
  • Rodrigo Gómez
    • 2
  • Elena Ibañez
    • 1
  • Lleonard Barrios
    • 1
  • Marta Duch
    • 2
  • Jaume Esteve
    • 2
  • José A. Plaza
    • 2
  • Carme Nogués
    • 1
  1. 1.Departament Biologia Cel·lular, Fisiologia i ImmunologiaUniversitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.Instituto de Microelectrónica de Barcelona (CNM-CSIC)BarcelonaSpain

Personalised recommendations