Materials and Designs for Multimodal Flexible Neural Probes

Part of the Microsystems and Nanosystems book series (MICRONANO)


The use of electrophysiology (EP) signals is the most relevant way to reflect biological activities in cells and tissues. In neuroscience, EP signals are standard indicators enable to display neural activities as action potentials. The action potentials are typically measured by the change of voltage or current from ion channels in the neurons. Usually, conductive electrodes formed on injectable probes that can be penetrated into deep brain tissue for recording EP signals. Over the last few decades, neural probes have been developed using microfabrication technology. Many researchers have attempted to develop and optimize various materials and designs of electrodes and neural probes to effectively minimize their invasive geometry with biocompatible materials. Compared to the rigid and non-flexible neural probes presented in the late 1980s, the shape of deformable neural probes, reported in the late 1990s, has many advantages. A multimodal function (i.e. electric recording with light or drug delivery) for optogenetics technique has also recently been developed as the next generation flexible neural probe. In this chapter, we deal with several examples of flexible neural probes (FNP) in terms of their geometry, materials, and functions. This study will facilitate a new paradigm for less invasive and more flexible multimodal neural probes that can be utilized in many research fields such as materials science, electrical engineering, and fundamental neuroscience.


Electrophysiological signal Flexible neural probe Stiffener Multimodal probe Optogenetics 


  1. 1.
    A. Altuna, G. Gabriel et al., SU-8-based microneedles for in vivo neural applications. J. Micromech. Microeng. 20, 064014 (2010)CrossRefGoogle Scholar
  2. 2.
    M. Asplund, E. Thaning et al., Toxicity evaluation of PEDOT/biomolecular composites intended for neural communication electrode. Biomed. Mater. 4, 045009 (2009)CrossRefGoogle Scholar
  3. 3.
    M. Bresadola, Medicine and science in the life of Luigi Galvani (1737–1798). Brain Res. Bull. 46, 367–380 (1998)CrossRefGoogle Scholar
  4. 4.
    P.K. Campbell, K.E. Jones et al., A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array. IEEE Trans. Biomed. Eng. 38, 758–768 (1991)CrossRefGoogle Scholar
  5. 5.
    A. Canales, X. Jia et al., Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nat. Biotech. 33, 277–284 (2015)CrossRefGoogle Scholar
  6. 6.
    J.A. Cardin, M. Carlén et al., Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nat. Protoc. 5, 247–254 (2010)CrossRefGoogle Scholar
  7. 7.
    C.H. Chen, S.C. Chuang et al., A three-dimensional flexible microprobe array for neural recording assembled through electrostatic actuation. Lab Chip 11, 1647–1655 (2011)CrossRefGoogle Scholar
  8. 8.
    M. Choi, J.W. Choi et al., Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo. Nat. Photon. 7, 987–994 (2013)CrossRefGoogle Scholar
  9. 9.
    S.L. Chorover, and A.M. Deluca, A sweet new multiple electrode for chronic single unit recording in moving animals. Physiol & Behav 9, 671–674 (1972)Google Scholar
  10. 10.
    K.L. Drake, K.D. Wise et al., Performance of planar multisite microprobe in recording extracellular single-unit intracortical activity. IEEE Trans. Biomed. Eng. 35, 719–732 (1988)CrossRefGoogle Scholar
  11. 11.
    S.H. Felix, K.G. Shah et al., Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive. Paper presented in international conference of the IEEE engineering in medicine and biology society, San Diego, 28 Aug–1 Sept 2012Google Scholar
  12. 12.
    C.P. Foley, N. Nishimura et al., Flexible microfluidic devices supported by biodegradable insertion scaffolds for convection-enhanced neural drug delivery. Biomed. Microdevices 11, 915–924 (2009)CrossRefGoogle Scholar
  13. 13.
    P.M. George, A.W. Lyckman et al., Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics. Biomaterials 26, 3511–3519 (2005)CrossRefGoogle Scholar
  14. 14.
    P.J. Gilgunn, R. Khilwani et al., An ultra-complaint, scalable neural probe with molded biodissolvable delivery vehicle. Paper presented at the MEMS 2012, Paris, 29 Jan–2 Feb 2012Google Scholar
  15. 15.
    A.E. Hess, J.R. Capadona et al., Development of a stimuli-responsive polymer nanocomposite toward biologically optimized, MEMS-based neural probes. J. Micromech. Microeng. 21, 054009 (2011)CrossRefGoogle Scholar
  16. 16.
    A. Jain, A.H.J. Yang et al., Gel-based optical waveguides with live cell encapsulation and integrated microfluidics. Opt. Lett. 37, 1472–1474 (2012)CrossRefGoogle Scholar
  17. 17.
    W. Jensen, K. Yoshida et al., In-vivo implant mechanics of flexible, silicon-based ACREO microelectrode arrays in rat cerebral cortex. IEEE Trans. Biomed. Eng. 53, 934–940 (2006)CrossRefGoogle Scholar
  18. 18.
    J.W. Jeong, J.G. McCall et al., Wireless optofluidic systems for programmable in vivo pharmacology and optogenetics. Cell 162, 662–674 (2015)CrossRefGoogle Scholar
  19. 19.
    M. Kang, S. Jung et al., Subcellular neural probes from single-crystal gold nanowires. ACS Nano 8, 8182–8189 (2014)CrossRefGoogle Scholar
  20. 20.
    B.J. Kim, J.T.W. Kuo et al., 3D Parylene sheath neural probe for chronic recordings. J. Neural Eng. 10, 045002 (2013)CrossRefGoogle Scholar
  21. 21.
    T.I. Kim, J.G. McCall et al., Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013)CrossRefGoogle Scholar
  22. 22.
    T.D.Y. Kozai, D.R. Kipke, Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain. J. Neurosci. Methods 184, 199–205 (2009)CrossRefGoogle Scholar
  23. 23.
    T.D.Y. Kozai, N.B. Langhals et al., Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nat. Mater. 11, 1065–1073 (2012)CrossRefGoogle Scholar
  24. 24.
    J.T.W. Kuo, B.J. Kim et al., Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration. Lab Chip 13, 554–561 (2013)CrossRefGoogle Scholar
  25. 25.
    G. Lind, C.E. Linsmeier et al., Gelatine-embedded electrode - a novel biocompatible vehicle allowing implantation of highly flexible microelectrodes. J. Neural. Eng. 7, 046005 (2010)Google Scholar
  26. 26.
    S. Kuppusami, R.H. Oskouei, Parylene coatings in medical devices and implants: a review. Univ. J. Biomed. Eng. 3, 9–14 (2015)Google Scholar
  27. 27.
    K.K. Lee, J. He et al., Polyimide-based intracortical neural implant with improved structural stiffness. J. Micromech. Microeng. 14, 32–37 (2004)CrossRefGoogle Scholar
  28. 28.
    D. Lewitus, K.L. Smith et al., Ultrafast resorbing polymers for use as carriers for cortical neural probes. Acta Biomater. 7, 2483–2491 (2011)CrossRefGoogle Scholar
  29. 29.
    W. Li, D.C. Rodger et al., Parylene-based integrated wireless single-channel neurostimulator. Sens. Actuator A 166, 193–200 (2011)CrossRefGoogle Scholar
  30. 30.
    J. Liu, T.M. Fu et al., Syringe-injectable electronics. Nat. Nanotechnol. 10, 629–636 (2015)CrossRefGoogle Scholar
  31. 31.
    J.G. McCall, T. Kim et al., Fabrication and application of flexible, multimodal light-emitting devices for wireless optogenetics. Nat. Protoc. 8, 2413–2428 (2013)CrossRefGoogle Scholar
  32. 32.
    A. Mercanzini, K. Cheung et al., Demonstration of cortical recording using novel flexible polymer neural probes. Sens. Actuators A 143, 90–96 (2008)CrossRefGoogle Scholar
  33. 33.
    I.R. Minev, P. Musienko et al., Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163 (2015)CrossRefGoogle Scholar
  34. 34.
    S.T. Parker, P. Domachuk et al., Biocompatible silk printed optical waveguides. Adv. Mater. 21, 2411–2415 (2009)CrossRefGoogle Scholar
  35. 35.
    P.J. Rousche, D.S. Pellinen et al., Flexible polyimide-based intracortical electrode arrays with bioactive capability. IEEE Trans. Biomed. Eng. 48, 361–371 (2001)CrossRefGoogle Scholar
  36. 36.
    B. Rubehn, S.B.E. Wolff et al., A polymer-based microimplant for optogenetic applications: design and first in vivo study. Lab Chip 13, 579–588 (2013)CrossRefGoogle Scholar
  37. 37.
    P. Stice, A. Gilletti et al., Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex. J. Neural Eng. 4, 42–53 (2007)CrossRefGoogle Scholar
  38. 38.
    T. Stieglitz, Flexible biomedical microdevices with double-sided electrode arrangements for neural applications. Sens. Actuators A 90, 203–211 (2001)CrossRefGoogle Scholar
  39. 39.
    T. Suzuki, D. Ziegler et al., Flexible neural probes with micro-fluidic channels for stable interface with the nervous system. Paper presented at the proceedings of the 26th annual international conference of the IEEE EMBS, San Francisco, 1–5 Sept 2004Google Scholar
  40. 40.
    D.H. Szarowski, M.D. Andersen et al., Brain responses to micro-machined silicon devices. Brain Res. 983, 23–35 (2003)CrossRefGoogle Scholar
  41. 41.
    S. Takeuchi, T. Suzuki et al., 3D Flexible multichannel neural probe array. J. Micromech. Microeng. 14, 104–107 (2004)CrossRefGoogle Scholar
  42. 42.
    S. Takeuchi, D. Ziegler et al., Parylene flexible neural probes integrated with microfluidic channels. Lab Chip 5, 519–523 (2005)CrossRefGoogle Scholar
  43. 43.
    L.W. Tien, F. Wu et al., Silk as a multifunctional biomaterial substrate for reduced glial scarring around brain-penetrating electrodes. Adv. Funct. Mater. 23, 3185–3193 (2013)CrossRefGoogle Scholar
  44. 44.
    A. Tooker, V. Tolosa et al., Polymer neural interface with dual-sided electrodes for neural stimulation and recording. Paper presented at the 34th annual international conference of the IEEE EMBS, San Diego, 28 Aug–1 Sept 2012Google Scholar
  45. 45.
    W.M. Tsang, A.L. Stone et al., Flexible split-ring electrode for insect flight biasing using multisite neural stimulation. IEEE Trans. Biomed. Eng. 57, 1757–1764 (2010)CrossRefGoogle Scholar
  46. 46.
    H.A.C. Wark, R. Sharma et al., A new high-density (25 electrodes/mm2) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures. J. Neural Eng. 10, 045003 (2013)CrossRefGoogle Scholar
  47. 47.
    A. Williamson, M. Ferro et al., Localized neuron stimulation with organic electrochemical transistors on delaminating depth probes. Adv. Mater. 27, 4405–4410 (2015)CrossRefGoogle Scholar
  48. 48.
    F. Wu, M. Im et al., A flexible fish-bone-shaped neural probe strengthened by biodegradable silk coating for enhanced biocompatibility. Paper presented in IEEE Transducers’11, Beijing, 5–9 June 2011Google Scholar
  49. 49.
    Z. Xiang, S.C. Yen et al., Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle. J. Micromech. Microeng. 24, 065015 (2014)CrossRefGoogle Scholar
  50. 50.
    H. Xin, Y. Li et al., Escherichia coli-based biophotonic waveguides. Nano Lett. 13, 3408–3413 (2013)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringSungkyunkwan University (SKKU)SuwonKorea
  2. 2.School of Chemical EngineeringSungkyunkwan University (SKKU)SuwonKorea
  3. 3.Center for Neuroscience Imaging Research (CNIR)Institute of Basic Science (IBS)SuwonKorea

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