Conductively coupled flexible silicon electronic systems for chronic neural electrophysiology

Abstract

Materials and structures that enable long-term, intimate coupling of flexible electronic devices to biological systems are critically important to the development of advanced biomedical implants for biological research and for clinical medicine. By comparison with simple interfaces based on arrays of passive electrodes, the active electronics in such systems provide powerful and sometimes essential levels of functionality; they also demand long-lived, perfect biofluid barriers to prevent corrosive degradation of the active materials and electrical damage to the adjacent tissues. Recent reports describe strategies that enable relevant capabilities in flexible electronic systems, but only for capacitively coupled interfaces. Here, we introduce schemes that exploit patterns of highly doped silicon nanomembranes chemically bonded to thin, thermally grown layers of SiO₂ as leakage-free, chronically stable, conductively coupled interfaces. The results can naturally support high-performance, flexible silicon electronic systems capable of amplified sensing and active matrix multiplexing in biopotential recording and in stimulation via Faradaic charge injection. Systematic in vitro studies highlight key considerations in the materials science and the electrical designs for high-fidelity, chronic operation. The results provide a versatile route to biointegrated forms of flexible electronics that can incorporate the most advanced silicon device technologies with broad applications in electrical interfaces to the brain and to other organ systems.

Keywords: bioelectronics; brain interface; flexible electronics; neuroscience.

Fig. 1.

Materials and integration strategies for use of monolithically bonded structures of highly doped Si NMs and thermally grown silicon dioxide (t-SiO₂) as electrical biointerfaces and biofluid barriers in flexible, biointegrated electronic systems. (A) Steps for forming structures of highly p-doped silicon (p⁺⁺-Si; boron at 10²⁰/cm³) as a conductive interface in a test platform: (A, I) doping and patterning regions of p⁺⁺-Si and n⁺⁺-Si on an SOI substrate; (A, II) fabricating active matrix circuits using an array of Si n-MOSFETs on the SOI; (A, III) bonding this circuit to a glass substrate coated with a film of polyimide (12 μm thick) and removing the Si wafer by dry etching; (A, IV) flipping the device over and forming "via" openings through the t-SiO₂ to locally expose the p⁺⁺-Si (the dashed line delineates the boundary of the unit cell); (A, V) depositing metal pads to seal the p⁺⁺-Si and peeling the device off from the handling substrate. (B) Sequence of optical images of a layer of Mg beneath a test device immersed in PBS solution (pH = 7.4) at 70 °C. The area inside of the blue rectangle corresponds to p⁺⁺-Si (thickness 170 nm). (C) Optical image of passive arrays of electrode encapsulated with p⁺⁺-Si (Left), electrochemical impedance spectra of a passive electrode (magnitude: black; phase: red) responses (Middle), and results of soak testing of a passive electrode in PBS at 96 °C showing that failure occurs at day 2.5 (Right).

Fig. 2.

Demonstration of flexible active electronics encapsulated with the p⁺⁺-Si // t-SiO₂ structure and analysis of leakage behaviors. (A and B) Results (subthreshold and leakage characteristics) from soak tests of a device with a p⁺⁺-Si via exposed to PBS solution at 96 °C. The results indicate stable operation until failure due to dissolution of the p⁺⁺-Si after 30 h. (C) Results from tests of a similar structure under identical conditions but with a coating of Au (300 nm) on the side of the system in contact with the PBS. Here, failure occurs at day 3. (D) Results from tests at different temperatures for structures with and without the Au coating. The lifetimes at 37 °C (156 and 285 d without and with the Au, respectively) correspond to extrapolations based on Arrhenius scaling from data collected at temperatures of 96, 70, and 65 °C for p⁺⁺-Si without the Au coating and of 96, 90, 70, and 60 °C for that with the Au.

Fig. 3.

Design and characterization of an actively multiplexed array of conductively coupled sensors for electrophysiological mapping, with the p⁺⁺-Si // t-SiO₂ structure as an interface. (A) Exploded view schematic illustrations of a system with 64 sensing nodes (i.e., channels). The labels highlight the different functional layers. (B) Photograph of a system in a slightly bent configuration. (C) Circuit diagram of a unit cell, with annotations for each component. (D) Optical microscope image of a sensing node before (Left) and after (Middle) deposition of a metal coating to define the sensing area (channel length L_eff = 16 μm, width W = 80 μm, thickness = 60 nm). The SEM image (Right) highlights the step edge between the t-SiO₂ and the p⁺⁺-Si in the via opening. (E) Transfer (Left) and output (Right) characteristics of a test transistor fabricated adjacent to the sensing matrix (Left, Inset). (F) Statistics of threshold voltages and peak effective mobilities of test transistors from 10 different samples. (G) Image of the experimental setup for the DAQ system. The device is completely immersed in PBS (pH = 7.4) at room temperature. (H) Output characteristics of a representative sensing node in response to an ac input of 2.8 mV at 10 Hz. (I) Spatial map of potential collected with a 64-channel device that has 100% yield.

Fig. 4.

In vitro measurements of the electrical performance of a conductively coupled sensing array with active multiplexed addressing. (A–C) Histogram of gain, noise, and signal-to-noise ratio associated with the 64 sensing nodes of a typical device. (D and E) Cumulative statistics of average gain and yield for 10 different systems of this type. (F–H) In vitro results from soak tests in PBS (pH = 7.4) at 96 °C, including yield, average gain, and noise amplitude. The performance remains stable until day 3, likely due to penetration of water through the perimeter edges of the system.

Fig. 5.

In vitro assessment of the efficiency and stability of stimulation electrodes of p⁺⁺-Si and comparisons to otherwise similar electrodes formed with thin films of Au. (A) Circuit diagram of the test system with annotations for each component. (B) Voltage output for input pulses of 10 V (20 Hz). (C) Impedance spectra of a p⁺⁺-Si electrode and a Au electrode before and after stimulation. (D) Data that illustrate the lifetimes of a p⁺⁺-Si electrode and a Au electrode operated at different simulation voltages.