Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

Abstract

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron–device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron–probe interactions, consistent with long-term biocompatibility of the device.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Macroporous nanoelectronic 3D neural probes.
Figure 2: Probe preparation and robustness.
Figure 3: Neural activity recording from rodent models.
Figure 4: Implanted macroporous nanoelectronic probe–tissue histology.

References

  1. 1

    Alivisatos, A. P. et al. Neuroscience. The brain activity map. Science 339, 1284–1285 (2013).

    CAS  Article  Google Scholar 

  2. 2

    Birmingham, K. et al. Bioelectronic medicines: A research roadmap. Nature Rev. Drug Discov. 13, 399–400 (2014).

    CAS  Article  Google Scholar 

  3. 3

    Shen, H. Neurotechnology: BRAIN storm. Nature 503, 26–28 (2013).

    CAS  Article  Google Scholar 

  4. 4

    Polikov, V. S., Tresco, P. A. & Reichert, W. M. Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods 148, 1–18 (2005).

    Article  Google Scholar 

  5. 5

    Olsen, S. R., Bortone, D. S., Adesnik, H. & Scanziani, M. Gain control by layer six in cortical circuits of vision. Nature 483, 47–52 (2012).

    CAS  Article  Google Scholar 

  6. 6

    Mizuseki, K., Diba, K., Pastalkova, E. & Buzsaki, G. Hippocampal CA1 pyramidal cells form functionally distinct sublayers. Nature Neurosci. 14, 1174–1181 (2011).

    CAS  Article  Google Scholar 

  7. 7

    Hochberg, L. R. et al. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375 (2012).

    CAS  Article  Google Scholar 

  8. 8

    Nicolelis, M. A. Actions from thoughts. Nature 409, 403–407 (2001).

    CAS  Article  Google Scholar 

  9. 9

    Taylor, D. M., Tillery, S. I. & Schwartz, A. B. Direct cortical control of 3D neuroprosthetic devices. Science 296, 1829–1832 (2002).

    CAS  Article  Google Scholar 

  10. 10

    Perlmutter, J. S. & Mink, J. W. Deep brain stimulation. Annu. Rev. Neurosci. 29, 229–257 (2006).

    CAS  Article  Google Scholar 

  11. 11

    Seymour, J. P. & Kipke, D. R. Neural probe design for reduced tissue encapsulation in CNS. Biomaterials 28, 3594–3607 (2007).

    CAS  Article  Google Scholar 

  12. 12

    Kozai, T. D. & Kipke, D. R. 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).

    CAS  Article  Google Scholar 

  13. 13

    HajjHassan, M., Chodavarapu, V. & Musallam, S. NeuroMEMS: Neural Probe Microtechnologies. Sensors 8, 6704–6726 (2008).

    CAS  Article  Google Scholar 

  14. 14

    Kozai, T. D. et al. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nature Mater. 11, 1065–1073 (2012).

    CAS  Article  Google Scholar 

  15. 15

    Seymour, J. P. & Kipke, D. R. Fabrication of polymer neural probes with sub-cellular features for reduced tissue encapsulation. Conf. Proc. IEEE Eng. Med. Biol. Soc. 1, 4606–4609 (2006).

    Article  Google Scholar 

  16. 16

    Kim, T. I. et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013).

    CAS  Article  Google Scholar 

  17. 17

    Sohal, H. S. et al. The sinusoidal probe: A new approach to improve electrode longevity. Front. Neuroeng. 7, 10 (2014).

    Article  Google Scholar 

  18. 18

    Nicolelis, M. A. et al. Chronic, multisite, multielectrode recordings in macaque monkeys. Proc. Natl Acad. Sci. USA 100, 11041–11046 (2003).

    CAS  Article  Google Scholar 

  19. 19

    Rousche, P. J. & Normann, R. A. Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex. J. Neurosci. Methods 82, 1–15 (1998).

    CAS  Article  Google Scholar 

  20. 20

    Kipke, D. R., Vetter, R. J., Williams, J. C. & Hetke, J. F. Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex. IEEE Trans. Neural Syst. Rehabil. Eng. 11, 151–155 (2003).

    Article  Google Scholar 

  21. 21

    Miller, K., Chinzei, K., Orssengo, G. & Bednarz, P. Mechanical properties of brain tissue in-vivo: Experiment and computer simulation. J. Biomech. 33, 1369–1376 (2000).

    CAS  Article  Google Scholar 

  22. 22

    Perge, J. A. et al. Intra-day signal instabilities affect decoding performance in an intracortical neural interface system. J. Neural Eng. 10, 036004 (2013).

    Article  Google Scholar 

  23. 23

    Biran, R., Martin, D. C. & Tresco, P. A. The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull. J. Biomed. Mater. Res. A 82, 169–178 (2007).

    Article  Google Scholar 

  24. 24

    Dickey, A. S., Suminski, A., Amit, Y. & Hatsopoulos, N. G. Single-unit stability using chronically implanted multielectrode arrays. J. Neurophysiol. 102, 1331–1339 (2009).

    Article  Google Scholar 

  25. 25

    Jackson, A. & Fetz, E. E. Compact movable microwire array for long-term chronic unit recording in cerebral cortex of primates. J. Neurophysiol. 98, 3109–3118 (2007).

    Article  Google Scholar 

  26. 26

    Tee, B. C., Wang, C., Allen, R. & Bao, Z. An electrically and mechanically self-healing composite with pressure- and flexion-sensitive properties for electronic skin applications. Nature Nanotech. 7, 825–832 (2012).

    CAS  Article  Google Scholar 

  27. 27

    Mannoor, M. S. et al. 3D printed bionic ears. Nano Lett. 13, 2634–2639 (2013).

    CAS  Article  Google Scholar 

  28. 28

    Jeong, J. W. et al. Soft materials in neuroengineering for hard problems in neuroscience. Neuron 86, 175–186 (2015).

    CAS  Article  Google Scholar 

  29. 29

    Spira, M. E. & Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nature Nanotech. 8, 83–94 (2013).

    CAS  Article  Google Scholar 

  30. 30

    Kruskal, P. B., Jiang, Z., Gao, T. & Lieber, C. M. Beyond the patch clamp: Nanotechnologies for intracellular recording. Neuron 86, 21–24 (2015).

    CAS  Article  Google Scholar 

  31. 31

    Tian, B. et al. Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nature Mater. 11, 986–994 (2012).

    CAS  Article  Google Scholar 

  32. 32

    Liu, J. et al. Syringe-injectable electronics. Nature Nanotech. 10, 629–636 (2015).

    CAS  Article  Google Scholar 

  33. 33

    Liu, J. et al. Multifunctional three-dimensional macroporous nanoelectronic networks for smart materials. Proc. Natl Acad. Sci. USA 110, 6694–6699 (2013).

    CAS  Article  Google Scholar 

  34. 34

    Lee, H., Bellamkonda, R. V., Sun, W. & Levenston, M. E. Biomechanical analysis of silicon microelectrode-induced strain in the brain. J. Neural Eng. 2, 81–89 (2005).

    Article  Google Scholar 

  35. 35

    Rousche, P. J. et al. Flexible polyimide-based intracortical electrode arrays with bioactive capability. IEEE Trans. Biomed. Eng. 48, 361–371 (2001).

    CAS  Article  Google Scholar 

  36. 36

    du Roure, O. et al. Force mapping in epithelial cell migration. Proc. Natl Acad. Sci. USA 102, 2390–2395 (2005).

    CAS  Article  Google Scholar 

  37. 37

    Sharp, A. A., Ortega, A. M., Restrepo, D., Curran-Everett, D. & Gall, K. In vivo penetration mechanics and mechanical properties of mouse brain tissue at micrometer scales. IEEE Trans. Biomed. Eng. 56, 45–53 (2009).

    Article  Google Scholar 

  38. 38

    Petersen, C. C. The functional organization of the barrel cortex. Neuron 56, 339–355 (2007).

    CAS  Article  Google Scholar 

  39. 39

    Boulton, A. A., Baker, G. B. & Vanderwolf, C. H. Neurophysiological Techniques (Humana Press, 1990).

    Google Scholar 

  40. 40

    Sheeba, J. H., Stefanovska, A. & McClintock, P. V. Neuronal synchrony during anesthesia: A thalamocortical model. Biophys. J. 95, 2722–2727 (2008).

    CAS  Article  Google Scholar 

  41. 41

    Kajikawa, Y. & Schroeder, C. E. How local is the local field potential? Neuron 72, 847–858 (2011).

    CAS  Article  Google Scholar 

  42. 42

    Stratton, P. et al. Action potential waveform variability limits multi-unit separation in freely behaving rats. PLoS ONE 7, e38482 (2012).

    CAS  Article  Google Scholar 

  43. 43

    Biran, R., Martin, D. C. & Tresco, P. A. Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp. Neurol. 195, 115–126 (2005).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank J. Tian for help and discussions on animal surgeries. This study was supported by Air Force Office of Scientific Research and NSSEFF awards (C.M.L.).

Author information

Affiliations

Authors

Contributions

C.X., J.L. and C.M.L. conceived the idea and designed the experiments. C.X., J.L., T.-M.F., X.D. and W.Z. performed the experiments and analyses. C.X. and C.M.L. wrote the manuscript. All authors discussed the results, interpreted the findings and reviewed the manuscript.

Corresponding authors

Correspondence to Chong Xie or Jia Liu or Tian-Ming Fu or Charles M. Lieber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 1953 kb)

Supplementary Information

Supplementary Movie 1 (MOV 3977 kb)

Supplementary Information

Supplementary Movie 2 (MOV 5204 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xie, C., Liu, J., Fu, T. et al. Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes. Nature Mater 14, 1286–1292 (2015). https://doi.org/10.1038/nmat4427

Download citation

Further reading

Search

Quick links

Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing