Research ArticleNEUROTECHNOLOGY

Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants

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Science Translational Medicine  16 Oct 2019:
Vol. 11, Issue 514, eaax9487
DOI: 10.1126/scitranslmed.aax9487
  • Fig. 1 Soft ABI electrode arrays conform to the curvature of the CN unlike the rigid electrode array of the clinical ABI.

    (A) Lateral view of an MRI reconstruction of the human brain with the brainstem shaded (blue). (B) Expanded view of the boxed region in (A), showing the position of the ABI electrode array between the cerebellum and the brainstem, in the lateral recess of the fourth ventricle. (C) Axial histological section of the brainstem with the dorsal and ventral subdivisions of the cochlear nucleus (DCN and VCN). The blue curve represents the soft electrode array conforming to the curved surface of the CN. The radius of curvature of the DCN (R) for this particular histological section was measured as 3 mm. (D) Photograph of one of the ABI electrode arrays currently in clinical use (Cochlear Ltd.). (E) Photograph showing the soft ABI conforming and the rigid clinical array not conforming to the curved surfaces of the right and left model DCNs, respectively. The agarose gel model is based on a 3D MRI reconstruction of the human brainstem. (F) Simulation results showing current density (black arrows) spreading in the cerebrospinal fluid and neural tissue upon stimulation (100 μA) using an electrode from a clinical ABI not completely in contact with the CN (left) and (G) an electrode from a soft ABI in contact with the CN (right). The colored surface shows an estimate of the tissue activation in both cases. Methodology is detailed in the “Simulation of cochlear nucleus electrical stimulation (surface of tissue activated)” section in the Supplementary Materials. (H) Top: Schematic representation of the soft ABI, a microstructured multilayer of PI and platinum forming the interconnects that are encapsulated between two layers of stretchable silicone. The electrodes sites are coated with a Pt-PDMS composite to decrease their impedance. Bottom: Photograph of the device with its connector. Scanning electron microscopy image of (I) the Pt-PDMS composite on the ABI electrode and (J) the microstructured multilayer in the interconnects. DCN, dorsal CN; VCN, ventral CN; S, superior; I, inferior; A, anterior; P, posterior; L, left; R, right.

  • Fig. 2 Electromechanical characteristics of stretchable materials used in the construction of soft ABI implants.

    (A) Micrograph of the Y-shaped motifs in a microstructured track. The red insets indicate the three independent geometrical parameters, a, r, and L, as well as the critical dimension (CD). (B) Mechanical simulation showing the local strain resulting from an applied strain (εapp) of 20% on a sheet of structured PI (left), and a photograph of a real sample stretched at 20% strain (right). (C) Graphical representation of the optimization study. Each dot represents a Y-shaped pattern with a different combination of parameters a and r (right). Three different designs are illustrated. (D) Change in electrical resistance as a function of stretching (10% applied strain) for 1000 cycles on microfabricated samples with all three designs. The study used PI/Pt/PI interconnects embedded in PDMS. (E) A microfabricated sample with (blue) and without (purple) microstructured Y-shaped cuts was stretched up to failure (indicated by a cross). The resistance is shown as a function of the applied strain (n = 2 samples, each with eight tracks 200 μm wide). (F) Measured force as a function of applied strain for the same samples as in (E). The red curve shows a free-standing sample of PDMS without embedded interconnects for comparison (n = 2 samples). (G) A sample was reversibly stretched to 10% for 1 million (1M) cycles. The graph shows the relative change in resistance as a function of the number of cycles. (H) Graph showing the theoretical thicknesses for which a rectangular sample of plain PDMS can conform to a specific wet cylinder of radius R. The left graph contains experimental dots representing samples of plain PDMS. The right graph contains experimental dots representing samples of 2-μm-thick microstructured multilayers of PI and platinum encapsulated between two layers of PDMS. The inset on the far right shows a photograph of an experimental sample of microstructured PI/Pt/PI embedded in 217-μm-thick PDMS conforming to an agarose cylinder of 4 mm in radius (arrow). (I) Electrical impedance norm (top) and phase (bottom) of the soft ABI electrodes measured in PBS as a function of frequency. Inset: Photograph of the microfabricated electrode contacts of the soft ABI. (J) Voltage measured on the soft ABI upon stimulation in PBS with a 1-mA biphasic current pulse (300 μm in width) at 100 Hz (n = 2 samples, with nine electrodes per device) using an external stimulator (Isolated Pulse Stimulator Model 2100, AM Systems). Shaded areas denote SD.

  • Fig. 3 Comparison of clinical and soft ABI electrode arrays in human cadavers.

    (A and B) Endoscopic view of a clinical ABI and soft ABI being inserted in the lateral recess of the fourth ventricle in a human cadaver. (C) Schematic (top) and photograph (bottom) of the soft ABI to which a hydrogel guide is glued on the back side of the electrode paddle. To adjust position of the ABI, the guide can be grasped by tweezers (right). (D) Endoscopic view of the insertion of the soft ABI with the guide being held by the tweezers. (E) Graph of the water mass intake of a mock-up soft ABI with the guide as a function of time (n = 5). The red dashed line denotes the moment at which the device is too soft to be inserted in a model of the lateral recess in agarose. (F and G) Impedance at 1 kHz for the clinical (green, n = 1 sample with nine electrodes) and soft (purple, n = 2 samples with nine electrodes each) ABIs measured in vitro in PBS before insertion, after insertion in the cadaver, and again in vitro after removal. (H) The voltage drop at the electrode interface upon electrical stimulation was extracted from the voltage transients, measured during stimulation, by removing the voltage drop in the interconnects (access resistance). Inset: Examples of voltage drop at the electrode interface for the clinical ABI (green) and the soft ABI (purple). Stimulation was performed with a biphasic symmetrical current pulse of 1 mA for the clinical ABI (green, n = 1 sample with nine electrodes) and soft ABI (purple, n = 2 sample with nine electrodes each). (I) Charge storage capacity extracted from the cyclic voltammogram of the clinical ABI (green) and soft ABI (purple). n = 1 sample with five electrodes each in both cases. Inset: Examples of cyclic voltammograms measured from a clinical ABI (green) and a soft ABI (purple). (J) CT scan of the cadaver implanted with a soft ABI, showing almost no artifact. (K) CT scan of a pediatric patient with a clinical ABI, showing substantial “windmill” artifact. All bars denote SD. A, anterior; P, posterior; L, left; R, right.

  • Fig. 4 Chronic functional tests of soft ABI electrode arrays in the mouse.

    (A) Photograph of the mouse ABI and images showing the microstructured tracks. The connector had pins for each of the three electrodes and a fourth pin to allow for control due to artifact stimulation. (B) 3D schematic of the ABI, showing the connector on the top of the head and the cable looping through a small posterior craniotomy to access the surface of the DCN as viewed through a second larger craniotomy. (C) Right: Surgical image of the ABI and its three electrodes (each of diameter 150 μm) on the surface of the DCN. Left: Illustration of the electrode array on an image of the CN, the latter generated using data of Muniak et al. (48). (D) Electrophysiological setup showing how stimulation of the CN was performed with biphasic current pulses (blue) applied to the electrodes of soft ABI. Responses recorded were (i) auditory brainstem responses (ABRs) recorded using surface electrodes on the vertex and left ear (top left), and (ii) neural responses recorded by a 16-channel penetrating probe in the inferior colliculus (IC), which receives crossing projections from the CN (diagram at right). Acoustic tones were used to calibrate the position of the probe. (E) Timeline of experiments. (F) Electrochemical impedance spectra (EIS) of electrodes in vitro (blue, n = 11), in vivo week 0 (black, n = 11), and in vivo week 4 (red, n = 12). Error bars denote SEM. (G) Mean impedance at 10 kHz (indicating the access resistance) at different time points for all electrodes. Error bars denote SD. Data extracted from four mice (four implants and three electrodes each). (H) Example waveforms of electrically evoked ABRs (eABRs) evoked by monopolar electrical stimulation of one electrode in a single mouse. The beginning of the traces (first millisecond) contains electrical stimulation artifacts and thus has been grayed out. (I) Example post-stimulus time histogram (PSTH) elicited by monopolar stimulation on week 0. (J) PSTH of the same mouse and same stimulation electrode on week 4. (K) Curves of IC activity for all stimulation electrodes across all mice. The bold curves show the average for weeks 0 (in black) and 4 (in red). n = 3 × 4 = 12. Bars denote SE. L, lateral; M, medial; A, anterior; P, posterior.

Supplementary Materials

  • stm.sciencemag.org/cgi/content/full/11/514/eaax9487/DC1

    Materials and Methods

    Fig. S1. Agarose mold of the human brainstem.

    Fig. S2. Simulation of CN electrical stimulation.

    Fig. S3. Process flow for microstructured PI/Pt/PI multilayer.

    Fig. S4. Electron microscopy of microstructured multilayers of PI/Pt/PI.

    Fig. S5. Geometric construction of the Y-shaped pattern.

    Fig. S6. Equivalent electrical circuit of microstructured electrical tracks.

    Fig. S7. Resistance of microstructured PI/Pt/PI tracks.

    Fig. S8. Electrical redundancy of tracks with Y-shaped micropatterns.

    Fig. S9. Critical dimension of the Y-shaped pattern.

    Fig. S10. Smallest theoretical track width of a microstructured interconnect.

    Fig. S11. Smallest practical track width of a microstructured interconnect.

    Fig. S12. Failure mechanisms of nonstructured PI/Pt/PI tracks compared to microstructured PI/Pt/PI tracks.

    Fig. S13. Electromechanical properties of microstructured tracks of varying width.

    Fig. S14. Apparent elastic modulus of microstructured tracks embedded in PDMS.

    Fig. S15. Conformability of membranes on wet cylinders.

    Fig. S16. Dimension comparison of the clinical and soft ABI.

    Fig. S17. Curvature measurements of the DCN surface from human histological slices.

    Fig. S18. Swelling over time of the hydrosoluble guide.

    Fig. S19. MRI comparison of the clinical and soft ABI in a cadaveric brain.

    Fig. S20. Electrical and dimensional layout of the mouse ABI electrode array.

    Fig. S21. Schematics and photographs of the surgical procedure of the mouse ABI electrode array implantation.

    Fig. S22. Examples of aABRs.

    Fig. S23. Comparison of neural recordings with a control not-connected pin.

    Fig. S24. PSTHs evoked by monopolar stimulation.

    Table S1. Parameters of electrical conductivity used for simulation.

    Table S2. Coordinates of the arcs defining the Y-shaped motifs.

    Table S3. Summary of results for the optimization study.

    Movie S1. Surgical approach using a rigid clinical ABI in a cadaveric specimen.

    Movie S2. Surgical approach using a soft ABI in a cadaveric specimen.

    Movie S3. Surgical approach using a soft ABI with temporary hydrosoluble guide in a cadaveric specimen.

    References (4952)

  • The PDF file includes:

    • Materials and Methods
    • Fig. S1. Agarose mold of the human brainstem.
    • Fig. S2. Simulation of CN electrical stimulation.
    • Fig. S3. Process flow for microstructured PI/Pt/PI multilayer.
    • Fig. S4. Electron microscopy of microstructured multilayers of PI/Pt/PI.
    • Fig. S5. Geometric construction of the Y-shaped pattern.
    • Fig. S6. Equivalent electrical circuit of microstructured electrical tracks.
    • Fig. S7. Resistance of microstructured PI/Pt/PI tracks.
    • Fig. S8. Electrical redundancy of tracks with Y-shaped micropatterns.
    • Fig. S9. Critical dimension of the Y-shaped pattern.
    • Fig. S10. Smallest theoretical track width of a microstructured interconnect.
    • Fig. S11. Smallest practical track width of a microstructured interconnect.
    • Fig. S12. Failure mechanisms of nonstructured PI/Pt/PI tracks compared to microstructured PI/Pt/PI tracks.
    • Fig. S13. Electromechanical properties of microstructured tracks of varying width.
    • Fig. S14. Apparent elastic modulus of microstructured tracks embedded in PDMS.
    • Fig. S15. Conformability of membranes on wet cylinders.
    • Fig. S16. Dimension comparison of the clinical and soft ABI.
    • Fig. S17. Curvature measurements of the DCN surface from human histological slices.
    • Fig. S18. Swelling over time of the hydrosoluble guide.
    • Fig. S19. MRI comparison of the clinical and soft ABI in a cadaveric brain.
    • Fig. S20. Electrical and dimensional layout of the mouse ABI electrode array.
    • Fig. S21. Schematics and photographs of the surgical procedure of the mouse ABI electrode array implantation.
    • Fig. S22. Examples of aABRs.
    • Fig. S23. Comparison of neural recordings with a control not-connected pin.
    • Fig. S24. PSTHs evoked by monopolar stimulation.
    • Table S1. Parameters of electrical conductivity used for simulation.
    • Table S2. Coordinates of the arcs defining the Y-shaped motifs.
    • Table S3. Summary of results for the optimization study.
    • Legends for movies S1 to S3
    • References (4952)

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Movie S1. Surgical approach using a rigid clinical ABI in a cadaveric specimen.
    • Movie S2. Surgical approach using a soft ABI in a cadaveric specimen.
    • Movie S3. Surgical approach using a soft ABI with temporary hydrosoluble guide in a cadaveric specimen.

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