Abstract
This study aims to investigate surface-modified microelectrodes on the microelectrode arrays (MEAs) for neuronal interfaces with in vitro cell culture. The polyimide (PI) MEA was fabricated by using micro-electro-mechanical systems (MEMS) techniques. Self-assembled monolayers (SAMs) of 11-mercaptoundecanoic acid (MUA) were utilized to modify the microelectrode surface of the MEA. The SAMs’ modified surface of microelectrodes offered a reliable interface to immobilize biological ligands through covalent bonding. To increase biocompatibility, the poly-d-lysine (PDL) was immobilized on the SAMs’ modified microelectrodes. Several analytical techniques were used to define the physical structure and functional groups of surface-modified gold microelectrodes on the MEA. Spectra of the Fourier transform infrared reflection (FTIR) were applied to characterize the molecular structure of MUA-SAMs and PDL on the microelectrodes. The spectra, two peaks of amide I (at 1,613 cm−1) and amide II (at 1,548 cm−1), revealed that covalent amide bonding existed in PDL-MUA-SAMs modified surfaces. The thickness and formation of the MUA and PDL were also observed and quantified by using an atomic force microscope (AFM). The impedance measurement of PDL-MUA-SAMs modified MEA only increased slightly to an average of 524.6 ± 55.8 kΩ from 352.9 ± 34.4 kΩ of bare gold microelectrode (p < 0.05, N = 20). In addition, the time-course changes of total impedance resulting from cell sealing resistance and gap reactance were recorded for 7 days for inferring the growth of cell lines on the electrode contact of modified MEA. The experiment of 3T3 fibroblasts, PC12 cells, primary glial cells, and primary cortical neurons cultured on the modified MEAs displayed a good adhesion rate. These biocompatibility assays demonstrated that the neuronal cells are able to grow in a proximity to PDL-MUA-SAMs modified microelectrodes of the MEAs for effective electrophysiological stimulation/sensing schemes and for future implantation purposes.
Similar content being viewed by others
References
J.R. Buitenweg, W.L.C. Rutten, E. Marani, S.K.L. Polman, J. Ursum, J. Neurosci. Methods 115, 211–221 (2002)
M. Chiappalone, A. Vato, M.B. Tedesco, M. Marcoli, F. Davide, S. Martinoia, Biosens. Bioelectron. 18, 627–634 (2003)
C.E.D. Chidsey, D.N. Loiacono, Langmuir 6, 682–691 (1990)
H.A. Chou, D.H. Zavitz, M. Ovadia, Biosens. Bioelectron. 18, 11–21 (2003)
K. Durick, P. Negulescu, Biosens. Bioelectron. 16, 587–592 (2001)
S. Flink, F.C.J.M. van Veggel, D.N. Reinhoudt, Adv. Mater. 12, 1315–1328 (2000)
M. Franco, P.F. Nealey, S. Campbell, A.I. Teixeira, C.J. Murphy, J. Biomed. Mater. Res. 52, 261–269 (2000)
R.I. Freshney, Culture of Animal Cells: A Manual of Basic Technique, 4th edn. (Wiley-Liss Press, New York, 2000), p. 177
P. Heiduschka, S. Thanos, Prog. Neurobiol. 55, 433–461 (1998)
S. Ingebrandt, C.K. Yeung, M. Krause, A. Offenhäusser, Biosens. Bioelectron. 16, 565–570 (2001)
H. Kaji, Y. Takii, M. Nishizawa, T. Matsue, Biomaterials 24, 4239–4244 (2003)
T.G. Kooten, H.T. Spijker, H.J. Busscher, Biomaterials 25, 1735–1747 (2004)
N. Lambeng, P.P. Michel, B. Brugg, Y. Agid, M. Ruberg, Brain Res. 821, 60–68 (1999)
S. Lan, M. Veiseh, M. Zhang, Biosens. Bioelectron. 20, 1697–1708 (2005)
J.D. Liao, S.P. Lin, Y.T. Wu, Biomacromolecules 6, 392–399 (2005)
Y.P. Liu, H.I. Lin, S.F. Tzeng, Brain Res. 1054, 152–158 (2005)
A.P. Marques, R.L. Reis, J.A. Hunt, Biomaterials 23, 1471–1478 (2002)
S. Martinoia, L. Bonzano, M. Chiappalone, M. Tedesco, M. Marcoli, G. Maura, Biosens. Bioelectron. 20, 2071–2078 (2005)
R.K. Mendes, R.S. Freire, C.P. Fonseca, S. Neves, L.T. Kubota, J. Braz. Chem. Soc. 15, 849–855 (2004)
A.L. Morales-Cruz, R. Tremont, R. Martínez, R. Romañach, C.R. Cabrera, Appl. Surf. Sci. 241, 371–383 (2005)
Y. Nam, D.W. Branch, B.C. Wheeler, Biosens. Bioelectron. 22, 589–597 (2006)
Y. Nam, J.C. Chang, B.C. Wheeler, G.J. Brewer, IEEE Trans. Biomed. Eng. 51, 158–165 (2004)
S.M. O’Connor, J.D. Andreadis, K.M. Shaffer, W. Ma, J.J. Pancrazio, D.A. Stenger, Biosens. Bioelectron. 14, 871–881 (2000)
T.J. O’Shaughnessy, B. Zim, W. Ma, K.M. Shaffer, D.A. Stenger, K. Zamani, G.W. Gross, J.J. Pancrazio, Brain Res. 959, 280–286 (2003)
B.D. Ratner, A.S. Hoffman, F.J. Schoen, J.E. Lemons, Biomaterials Science: An Introduction to Materials in Medicine. (Academic, San Diego, 1996), p. 165
E.V. Romanova, S.P. Oxley, S.S. Rubakhin, P.W. Bohn, J.V. Sweedler, Biomaterials 27, 1665–1669 (2006)
W. Rutten, J.M. Mouveroux, J. Buitenweg, C. Heida, T. Ruardij, E. Marani, E. Lakke, Proc. IEEE 89, 1013–1029 (2001)
W.L.C. Rutten, J.P.A. Smit, T.A. Frieswijk, J.A. Bielen, A.L.H. Brouwer, J.R. Buitenweg, C. Heida, IEEE Eng. Med. Biol. Mag. 47–55 (1999)
M.H. Schoenfisch, M. Ovadia, J.E. Pemberton, J. Biomed. Mater. Res. 51, 209–215 (2000)
A. Singh, G. Ehteshami, S. Massia, J.P. He, R.G. Storer, G.B. Raupp, Biomaterials 24, 5083–5089 (2003)
G.E. Slaughter, E. Bieberich, G.E. Wnek, K.J. Wynne, A. Guiseppi-Elie, Langmuir 20, 7189–7200 (2004)
R.K. Smith, P.A. Lewis, P.S. Weiss, Prog. Surf. Sci. 75, 1–68 (2004)
D.A. Stenger, G.W. Gross, E.W. Keefer, K.M. Shaffer, J.D. Andreadis, W. Ma, J.J. Pancrazio, Trends Biotechnol. 19, 304–309 (2001)
A. Ulman, Chem. Rev. 96, 1533–1554 (1996)
T. Yagi, Y. Ito, H. Kanda, S. Tanaka, M. Watanabe, Y. Uchikawa, in Systems, Man, and Cybernetics, 1999, IEEE SMC ‘99 Conference Proceedings (IEEE, Tokyo, 1999), p. 382
C.M. Yam, L. Zheng, M. Salmain, C.M. Pradier, P. Marcus, G. Jaouen, Colloids Surf. B Biointerfaces 21, 317–327 (2001)
Acknowledgements
This work was supported by the National Science Council of Taiwan under contract number NSC 94-2213-E-006-115. Technical support to fabricate the microelectrode was given by the Micro-Nano Technology Research Center, National Cheng Kung University, and the Southern Region Micro-Electro-Mechanical System Research Center in Tainan, Taiwan.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lin, SP., Chen, JJ.J., Liao, JD. et al. Characterization of surface modification on microelectrode arrays for in vitro cell culture. Biomed Microdevices 10, 99–111 (2008). https://doi.org/10.1007/s10544-007-9114-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-007-9114-y