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SCIENCE CHINA Information Sciences, Volume 64 , Issue 12 : 221401(2021) https://doi.org/10.1007/s11432-021-3321-7

Long-term flexible penetrating neural interfaces: materials, structures, and implantation

Chi GU 1,2, Jianjuan JIANG 1, Tiger H. TAO 1,2,3,4,5,6,7,*, Xiaoling WEI 1,2,*, Liuyang SUN 1,2,5,6,7,*
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  • ReceivedMay 22, 2021
  • AcceptedAug 16, 2021
  • PublishedOct 20, 2021

Abstract


Acknowledgment

This work was partially supported by National Science and Technology Major Project from Minister of Science and Technology, China (Grant Nos. 2020AAA0130100, 2018AAA0103100, 2019YFA0905200), National Science Fund for Excellent Young Scholars (Grant No. 61822406), National Natural Science Foundation of China (Grant Nos. 61974154, 61904187), Key Research Program of Frontier Sciences, CAS (Grant No. ZDBS-LY-JSC024), CAS Pioneer Hundred Talents Program, Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX01), Shanghai Outstanding Academic Leaders Plan (Grant No. 18XD1404700), Shanghai Pujiang Program (Grant No. 19PJ1410900), Shanghai Sailing Program (Grant No. 19YF1456700), and Youth Innovation Promotion Association CAS (Grant No. 2019236).


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  • Figure 1

    (Color online) Schematic diagram of the development strategy for long-term flexible penetrating neural interfaces. Surface modification: reproduced with permission [15]@Copyright 2017 Elsevier Science. Neural electrode: reproduced with permission [16]@Copyright 2015 Springer Nature. Multifunction: reproduced with permission [17]@Copyright 2018 American Chemical Society. Shuttle device: reproduced with permission [18]@Copyright 2019 IOP Publishing. Sacrifice layer: reproduced with permission [19]@Copyright 2019 American Association for the Advancement of Science. Variable rigidity: reproduced with permission [20]@Copyright 2020 Royal Society of Chemistry. Chronic flexible PNI: reproduced with permission [21]@Copyright 2017 American Chemical Society. Reproduced with permission [22]@Copyright 2017 American Association for the Advancement of Science.

  • Figure 2

    Table of content of this review.

  • Figure 3

    (Color online) Long-term penetrating flexible neural interface based on polymer materials. (a) SU-8; (b) Parylene C; (c) PI; (d) PDMS. Scale bars: (a) 50 $\mu$m; (b) 5 mm; (c) 150 $\mu$m; (d) 2 mm. (a) Reproduced with permission [27]@Copyright 2018 Wiley. (b) Reproduced with permission [43]@Copyright 2016 IOP Publishing. (c) Reproduced with permission [50]@Copyright 2020 IOP Publishing. (d) Reproduced with permission [51]@Copyright 2013 Elsevier Science.

  • Figure 4

    (Color online) Surface modification of long-term flexible penetrating neural interface. (a) The impedance of 16 electrodes modified with PEDOT at 1 kHz varies with time immersed in ACSF solution. (b) SEM images of PEDOT-modified electrodes before and after implantation in a mouse hippocampus for 30 weeks. (c) Firing rate and SNR of electrophysiological signals recorded under different conditions, such as Caveolin-1 virus transcription, Matrigel coating, and control. (d) SNR of the signal changes over time under different conditions, such as Caveolin-1 virus transcription, Matrigel coating, and control. Scale bar: (b) white: 10 $\mu$m, black: 100 $\mu$m. (a) and (b) Reproduced with permission [15]@Copyright 2017 Elsevier Science. (c) and (d) Reproduced with permission [43]@Copyright 2016 IOP Publishing.

  • Figure 5

    (Color online) NET and NET-e probes with neuroelectric signal recording function. (a) Optical image of NET probe. (b) Above: impedance (red) and noise level (blue) of NET probe as a function of time. Below: number and percentage of electrodes that recorded unit activities (red) and sortable single-unit APs (orange) of the NET probe as a function of time. (c) Three-dimensional reconstruction of two-photon imaging after NET implantation. (d) Microscope image of EBL section of the NET-e probe. (e) Spikes recorded by NET-e probe over eight weeks post-implantation. Scale bar: (a) 100 $\mu$m; (c) 50 $\mu$m; (d) left: 20 $\mu$m, right: 10 $\mu$m; (e) vertical: 50 $\mu$V, horizontal: 0.5 ms. (a)–(c) Reproduced with permission [22]@Copyright 2017 American Association for the Advancement of Science. (d)–(e) Reproduced with permission [27]@Copyright 2018 Wiley.

  • Figure 6

    (Color online) Mesh neural interface with neural electric signal recording function. (a) Fluorescence microscope image of neuron cell and SEM image of NeuE. (b) Bending stiffness of axons, NeuE and previous mesh neural interface. (c) Spikes recorded by NeuE over 90 days post implantation. (d) Three-dimensional reconstruction of two-photon imaging of NeuE after implantation. (e) Microscope image of 1D and 2D mesh neural interface injected into agarose hydrogel. (f) Cross-sectional diameters of 1D and 2D mesh neural interfaces. (g) and (h) Microscope image of 3D mesh neural interface. Scale bars: (a) 10 $\mu$m; (d) 200 $\mu$m; (g) 200 $\mu$m; (h) 50 $\mu$m. (a)–(d) Reproduced with permission [81]@Copyright 2019 Springer Nature. (e) and (f) Reproduced with permission [84]@Copyright 2019 American Chemical Society. (g) and (h) Reproduced with permission [16]@Copyright 2015 Springer Nature.

  • Figure 7

    (Color online) Realization of a multifunctional neural interface based on NEC. (a) Schematic diagram of NEC integration with optical fiber and glass pipettes; (b) microscope image of NEC integration with optical fiber and glass pipettes; (c) demonstration of electrophysiological recording of neuronal cells combined with optical or drug regulation. Scale bars: (b) 100 $\mu$m; (c) top: 2 s, bottom: 1 min. Reproduced with permission [21]@Copyright 2017 American Chemical Society.

  • Figure 8

    (Color online) Multifunctional fiber probe based on TDP. (a) Schematic diagram of the fiber probe manufacturing process; (b) image of the TDP process; (c) optical image of fiber probe cross-section; (d) image of light traveling along the fiber probe; (e) simultaneous optogenetic stimulation (blue marks) and electrophysiological recording performed two days, one week, one month and two months after implantation; (f) schematic diagram of the LED chip integration process; (g) LED chip integration allows light stimulation. (a)–(e) Reproduced with permission [85]@Copyright 2015 Springer Nature. (f) and (g) Reproduced with permission [90]@Copyright 2018 Springer Nature.

  • Figure 9

    (Color online) Flexible probe implantation method based on shuttle device. (a) Schematic diagram of manual implantation method based on tungsten wire; (b) microscope image of flexible probe assembly with tungsten wire; (c)–(f) image of parallel implantation based on additional shuttle device carrying chips; (g) and (h) image of parallel implantation based on PTFE microtubes; (i) and (j) image of the surgical robot; (k) image of the probe implantation process based on the surgical robot. Scale bars: (b) 500 $\mu$m, insert: 2 $\mu$m; (c) 500 $\mu$m; (d) 50 $\mu$m; (e)–(h) 500 $\mu$m. (a) and (b) Reproduced with permission [22]@Copyright 2017 American Association for the Advancement of Science. (c)–(h) Reproduced with permission [18]@Copyright 2019 IOP Publishing. (i)–(k) Reproduced with permission [97]@Copyright 2019 J M I R Publications, Inc.

  • Figure 10

    (Color online) Implantation of a flexible neural interface based on a sacrificial layer that can be degraded in vivo. (a) Schematic diagram and (b) microscope image of flexible neural probes self-assembled into bundles. (c) Microscope image of brain slice and implanted neural interface. (d) Microscope image of E5005(2K) sacrificial layer. (e) Buckling force as a function of E5005(2K) sacrificial layer thickness. (f) Relative mass retention of the E5005(2K) sacrificial layer as a function of implantation time. (g) SEM image of the CMC sacrificial layer. (h) Images of NeuN (green), Neurofilament (red), BBB Leakage (IgG, white), and cell nuclei (blue) after implantation of CMC sacrificial layer and microwire for 1, 7, 28, and 84 days. Scale bar: (b) left: 100 $\mu$m, right: 500 $\mu$m; (c) 500 $\mu$m; (d) 200 $\mu$m. (a)–(c) Reproduced with permission [19]@Copyright 2019 American Association for the Advancement of Science. (d)–(f) Reproduced with permission [29]@Copyright 2015 Springer New York LLC. (g) and (h) Reproduced with permission [98]@Copyright 2014 Pergamon.

  • Figure 11

    (Color online) Neural interface with variable rigidity before and after implantation. (a) Fiber probe based on calcium cross-linked sodium alginate before and after reaction with water; (b) stress of the fiber probe under different reaction times as a function of displacement; (c) Young's modulus of Au wire, Dry-MFNP, Wet-MFNP and brain tissue; (d) schematic diagram of the Ga-based rigid variable probe; (e) schematic diagram of Ga-based probes recovering flexibility after insertion into agar; (f) and (g) images of Ga-based probes in rigid and flexible states. Scale bar: (f) and (g) 500 $\mu$m. (a)–(c) Reproduced with permission [20]@Copyright 2020 Royal Society of Chemistry. (d)–(g) Reproduced with permission [101]@Copyright 2019 Elsevier Science.

  • Table 1  

    Table 1Material properties of brain tissue, silicon and various polymers [27,28]

    Young's Density Melting/thermal Possible thicknessesUSP class
    Modudus (GPa)(g$\cdot~$cm$^{-3}$)decomposition temperature (${^\circ}$)($\mu~$m)
    Polyimide8.831.10–1.11$>$5501–15
    PDMS0.5$\times~$10$^{-3}$–0.11.08$\sim~$25010–100 (spin coating)VI
    Parylene C3.21.2892901–100VI
    SU-80.021.075–1.238300–3150.5–300
    Human brain1$\times~$10$^{-6}$–0.11.039–1.043
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