Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo

Journal name:
Nature Neuroscience
Year published:
Published online


Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

At a glance


  1. Flexible, high-resolution multiplexed electrode array.
    Figure 1: Flexible, high-resolution multiplexed electrode array.

    (a) Photograph of a 360-channel high-density active electrode array. The electrode size and spacing was 300 × 300 μm and 500 μm, respectively. Inset, a closer view showing a few unit cells. (b) Schematic circuit diagram of single unit cell containing two matched transistors (left), transfer characteristics of drain-to-source current (Id) from a representative flexible transistor on linear (blue) and logarithmic (red) scales as gate to source voltage (Vg) was swept from −2 to +5 V, demonstrating the threshold voltage (Vt) of the transistor (center). Right, current-voltage characteristics of a representative flexible silicon transistor. Id was plotted as a function of drain-to-source voltage (Vd). Vg was varied from 0 to 5 V in 1-V steps. (c) Schematic exploded view (left) and corresponding microscope image of each layer: doped silicon nanoribbons (right frame, bottom), after vertical and horizontal interconnection with arrows indicating the first and second metal layers (ML, right frame, second from bottom), after water-proof encapsulation (right frame, third from bottom) and after platinum electrode deposition (right frame, top). Green dashed lines illustrated the offset via structure, critical for preventing leakage current while submerged in conductive fluid. (d) Images of folded electrode array around low modulus polydimethylsiloxane (PDMS) insert. (e) Bending stiffness of electrode array for varying epoxy thicknesses and two different polyimide (PI) substrate thicknesses. A nearly tenfold increase in flexibility between the current device and our prior work was shown. (f) Induced strain in different layers depending on the change in bending radius.

  2. Animal experiment using feline model.
    Figure 2: Animal experiment using feline model.

    (a) A flexible, high-density active electrode array was placed on the visual cortex. Inset, the same electrode array was inserted into the interhemispheric fissure. (b) Left, folded electrode array before insertion into the interhemispheric fissure. Right, flat electrode array inserted into the interhemispheric fissure.

  3. Spontaneous barbiturate-induced sleep spindles.
    Figure 3: Spontaneous barbiturate-induced sleep spindles.

    (a) A typical spindle recorded from a representative channel. Negative is plotted up by convention. Arrows point to individual spikes of the spindle (I–IV) that were further analyzed. (b) r.m.s. value of the zero-meaned signal of individual sharply contoured waves comprising the spindle revealed the high sensitivity of the electrode array and the spatially localized nature of spindles (left column), as well as the high degree of temporal synchronization indicated by the relative time to peak across the array (right column). Data are anatomically orientated as shown in the inset of Figure 4b.

  4. Visual evoked response analysis to a two-dimensional sparse noise visual stimulus.
    Figure 4: Visual evoked response analysis to a two-dimensional sparse noise visual stimulus.

    (a) 64-color maps, each showing the response (r.m.s. value of the zero-meaned signal in the response window) of the entire 360-channel electrode array. The color maps are arranged in the same physical layout as the stimuli were presented on the monitor, that is, the image map in the upper left-hand corner of the figure represents the neural response across the entire array to a flashing box presented in the upper left-hand corner of the monitor. The color scale is constant over all 64 image maps and is saturated at the 1st and 99th percentile to improve the visual display. (b) 64-color maps generated from the same response data as in a, but plotting the response latency. Channels that did not show a strong response, as determined by exceeding 50% of the maximum evoked response, were excluded and are colored white. Inset, exploded view illustrates the anatomical orientation of the electrode array on the brain and approximate location of Brodmann's areas (gray numbers and dashed lines). The electrode color map data is oriented such that the bottom left-hand corner of the electrode array was approximately located over Brodmann area 18, the bottom right-hand corner over area 17, the middle region over areas 18 and 19, the upper right-hand corner over area 21 and upper left-hand corner over area 7. (c) Performance results achieved after subjecting a test set of data to a DBN classifier in accurately determining each originating location on the screen of respective stimuli. 23 of the 64 screen locations (36%) were predicted exactly correct (black boxes), significantly better than chance (binomial distribution, n = 64, p = 1/64, P(x > 22) << 0.0001%). 42 of 64 (66%) screen locations were predicted correctly in one neighboring square (gray boxes, distance chance level 11.8%).

  5. Detailed two-dimensional data from electrographic seizures in feline neocortex.
    Figure 5: Detailed two-dimensional data from electrographic seizures in feline neocortex.

    (a) μECoG signal from a representative channel of the electrode array during a short electrographic seizure. Negative is plotted up by convention. Labeled segments correspond to movie frames below. (b) Movie frames show varied spatial-temporal μECoG voltage patterns from all 360 electrodes during the labeled time intervals from a. The frame interval and color scale are provided for each set of eight movie frames and the color scale is saturated at the 2nd and 98th percentile over eight frames to improve the visual display. Data are anatomically orientated as shown in the inset of Figure 4b. (c) Relative delay map for the 4–8 Hz band-pass filtered data from 3 s of continuous clockwise spiral rotations (b, waveform IV) illustrating a clear phase singularity and counter clockwise rotation. (d) Relative delay map for narrow band-pass filtered data from ~0.5 s of clockwise spiral rotations (b, waveform II) illustrating clockwise rotation, but a less clear singularity. (e) Representative delay image maps from six different spike clusters are shown to illustrate the differences between clusters (left columns). The average waveform for the corresponding spike (red traces, right columns) illustrates that complicated spatial patterns at the micro scale (0.5 mm) can be indistinguishable at the current clinical scale (~10 mm). Numerals I, III and V indicate the clusters that the corresponding waves in b belong to. (f) Representative delay image maps from two clusters that occurred almost exclusively during seizures, illustrating striking differences in spatial-temporal micro-scale patterns during seizures.


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Author information

  1. These authors contributed equally to this work.

    • Jonathan Viventi &
    • Dae-Hyeong Kim


  1. Department of Electrical and Computer Engineering, Polytechnic Institute of New York University, Brooklyn, New York, USA.

    • Jonathan Viventi
  2. Center for Neural Science, New York University, New York, New York, USA.

    • Jonathan Viventi
  3. School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.

    • Dae-Hyeong Kim
  4. Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

    • Leif Vigeland,
    • Larry Palmer &
    • Diego Contreras
  5. Penn Epilepsy Center, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Eric S Frechette,
    • Kathryn Davis &
    • Brian Litt
  6. Department of Electrical and Computer Engineering, United States Naval Academy, Annapolis, Maryland, USA.

    • Justin A Blanco
  7. Department of Materials Science and Engineering, Beckman Institute for Advanced Science and Technology and Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

    • Yun-Soung Kim,
    • Suk-Won Hwang &
    • John A Rogers
  8. Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Andrew E Avrin &
    • Jan Van der Spiegel
  9. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Vineet R Tiruvadi,
    • Ann C Vanleer,
    • Drausin F Wulsin,
    • Casey E Gelber &
    • Brian Litt
  10. Department of Engineering Mechanics, Tsinghua Univeristy, Beijing, China.

    • Jian Wu
  11. Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado, USA.

    • Jianliang Xiao
  12. Departments of Civil and Environmental Engineering and Mechanical Engineering, Northwestern University, Evanston, Illinois, USA.

    • Yonggang Huang


J.V., D.-H.K., L.V., A.E.A., V.R.T., L.P., J.V.S., D.C., J.A.R. and B.L. designed the experiments. J.V., D.-H.K., L.V., J.A.B., Y.-S.K., S.-W.H., A.C.V., D.F.W., K.D., E.S.F., C.E.G., R.Y., J.W. and J.X. performed the experiments and analysis. J.V., D.-H.K., L.V., J.A.B., E.S.F., Y.H., D.C., J.A.R. and B.L. wrote the paper.

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The authors declare no competing financial interests.

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Supplementary information

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  1. Supplementary Text and Figures (12M)

    Supplementary Figures 1–27


  1. Supplementary Movie 1 (31M)

    Movie of a short electrographic seizure showing numerous complicated spatial patterns, including clockwise and counterclockwise spiral waves. The voltage for all 360 channels is plotted as a color map in the top of the frame, while the average of all 360 electrodes is plotted at the bottom of the frame with a vertical bar indicating the position in time for reference. The movie is presented ~18× slower than real-time.

Additional data