Wide bandgap semiconductor nanomembranes as a long-term biointerface for flexible, implanted neuromodulator

Abstract

Electrical neuron stimulation holds promise for treating chronic neurological disorders, including spinal cord injury, epilepsy, and Parkinson's disease. The implementation of ultrathin, flexible electrodes that can offer noninvasive attachment to soft neural tissues is a breakthrough for timely, continuous, programable, and spatial stimulations. With strict flexibility requirements in neural implanted stimulations, the use of conventional thick and bulky packages is no longer applicable, posing major technical issues such as short device lifetime and long-term stability. We introduce herein a concept of long-lived flexible neural electrodes using silicon carbide (SiC) nanomembranes as a faradic interface and thermal oxide thin films as an electrical barrier layer. The SiC nanomembranes were developed using a chemical vapor deposition (CVD) process at the wafer level, and thermal oxide was grown using a high-quality wet oxidation technique. The proposed material developments are highly scalable and compatible with MEMS technologies, facilitating the mass production of long-lived implanted bioelectrodes. Our experimental results showed excellent stability of the SiC/silicon dioxide (SiO₂) bioelectronic system that can potentially last for several decades with well-maintained electronic properties in biofluid environments. We demonstrated the capability of the proposed material system for peripheral nerve stimulation in an animal model, showing muscle contraction responses comparable to those of a standard non-implanted nerve stimulation device. The design concept, scalable fabrication approach, and multimodal functionalities of SiC/SiO₂ flexible electronics offer an exciting possibility for fundamental neuroscience studies, as well as for neural stimulation-based therapies.

Keywords: bioencapsulation; flexible electronics; implanted applications; long-term stability; neuron modulators.

Fig. 1.

Implanted SiC electronics for the nerve stimulation protocol. (A) Concept of SiC/SiO₂ electronics for neuromodulation, promoting the recovery of motor and physiological functions. (B) Schematic illustration of the flexible SiC/SiO₂ wrapped around a sciatic nerve for long-term electrical stimuli and sensing. (C) Exploded view of the proposed flexible SiC/SiO₂ bioelectronic system (Al: aluminum).

Fig. 2.

Characterization of the SiC/SiO₂ platform fabricated with a CMOS-compatible thermal oxidation process. (A) Colorimetric observation under optical microscopy indicates no color change for SiC after the thermal oxidation for 5 h, while Si clearly changed from purple to light blue (scale bar, 100 µm). (B) Atomic force microscopy inspection of SiC surface morphology before and after the oxidation process. (C) I-V characteristics of SiC after oxidation. Inset: Thickness of SiC before and after oxidation. (D) Step height change after oxidation for SiC-patterned samples. (E) Uniformity of SiO₂ thickness across a 6-inch SiC-on-Si wafer after oxidation.

Fig. 3.

Long-term stability characterizations of flexible SiC/SiO₂ electronics. (A) Structured SiC and metal on a Si substrate by CMOS processes. (B) Transferred SiC/metal onto polyimide substrate. (C) Bendability when wrapped around a glass tube (scale bar, 10 mm). (D) Cross-sectional view of flexible SiC electronics after SiO₂ passivation and metallization. (E) Electrical conductivity measurement of SiC during the buckling test (scale bar, 10 mm). (F) I-V characteristics of SiC after 1,000 bending cycles (cyc: cycle). (G) Soaking test of hydrolysis in SiC and as-grown SiO₂ in PBS 1X at various temperatures up to 96 °C. (H) SiC thickness and electrical resistance variations after the accelerated hydrolysis test in PBS at 96 °C after up to 14 days. (I) Optical reflectance of SiC after soaking in PBS 1X at 96 °C for 7 and 14 days. (J) Depth profile scan of SiO₂ in PBS 1X at 96 °C for up to 7 days. (K) Thickness changes of SiO₂ in PBS 1X at 96, 80, 65, and 50 °C for up to 7 days.

Fig. 4.

Multimodal SiC/SiO₂ bioelectrodes and integrated sensors. (A) Optical photograph of fabricated SiC electrodes incorporated with metal contact (scale bar, 1 mm). (B) EIS of single-crystal SiC electrodes: impedance and phase angle versus frequency from 100 Hz to 1 MHz and electrode size of 900 × 200 µm² (Z: impedance). (C) CV scan of an SiC electrode in 0.1 M PBS (pH 7.4) at a scan rate of 0.1 V s⁻¹. (D) Biosimulated measurement with a Pt reference electrode in 0.1 M PBS (scale bar, 5 mm). (E) Transmission efficiency of alternating current (ac) electrical stimulation (V_pp: peak-to-peak voltage). (F) Matching output voltage with an applied ac signal at 20 Hz. (G and H) Stimulated monophasic experiment. (G) Experimental apparatus (scale bar, 10 mm). (H) Comparison between input and output signals. (I) Demonstration of an integrated temperature sensor (scale bar, 500 µm). (J) Contact sensing with a hydrogel model using SiC electrodes.

Fig. 5.

(A–C) Biocompatibility experiment. The SiC material did not elicit cytotoxicity in the HMF. Fluorescence images: (A) Actin stained in green. (B) Nucleus stained in blue. (C) Merged cells: actin (green) and nucleus (blue) shows the cell attachment and spreading with their general morphology (scale bar, 50 µm). (D–I) Demonstration of in vivo muscle stimulation using an implanted SiC electrode. (D) Left: Schema of electrical muscle stimulation on a rat sciatic nerve model. Right: Photograph of flexible SiC/SiO₂ wrapped around the rat sciatic nerve (scale bar, 5 mm). (E) Left: Recorded CMAP signal from a transcutaneous surface electrode with different applied stimulating currents from 0.07 to 0.25 mA using the SiC electrode. Right: CMAP output waveforms (not to scale) (a.u.: arbitrary unit). (F) Recorded voltage amplitude at different applied pulse currents to SiC stimulation electrodes. Up: Overlaying the CMAP response under different stimuli. Down: Relationship between input current and output CMAP. (G) Leg movement at the knee joint with an angle of >15°. (H and I) Benchmarking stimulation of SiC versus standard gold electrodes. (H) Amplitude at CMAP supramaximal stimulation (mean ± standard error mean (SEM)) with significance values (***P < 0.001, one-tailed t-test) and (I) CMAP duration at supramaximal stimulation (mean ± SEM) and significance values (**P < 0.01, one-tailed t-test) using SiC stimulation electrodes.