Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics

Abstract

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

Figure 1. Schematic illustration and images corresponding to steps for fabricating conformal silk-supported PI electrode arrays

a, Casting and drying of silk fibroin solution on a temporary substrate of PDMS; 5–15 μm thick silk film after drying for 12 hours at room temperature. b, Steps for fabricating the electrode arrays, transfer printing them onto silk, and connecting to ACF cable. c, Schematic illustration of clinical usage of a representative device in an ultrathin mesh geometry with dissolvable silk support.

Figure 2. Time dependent changes as the silk substrate dissolves

a, Dissolution of the silk via submersion in warm water. b, Total bending stiffness of 7 μm and 2.5 μm electrode arrays on supporting silk films as a function of thickness of the supporting silk film; inset shows the ratio of bending stiffness between 7 μm and 2.5 μm. c, Time dependent change in volume of a silk film during dissolution (left frame) and bending stiffness calculated for silk treated in 70% ethanol for 5 seconds for two different array thicknesses (right frame). The 5 second ethanol treatment increases the dissolution time from minutes to about 1 hour.

Figure 3. Neural electrode arrays of varying thickness on simulated brain models to illustrate flexibility

a, Schematic illustration of trends in thickness and structure that improve conformal contact. b, Series of pictures illustrating how the thickness of the electrode array contributes to conformal contact on a brain model. c, Magnified view of these pictures. d, Image of an electrode array with a mesh design on dissolvable silk substrate. Arrows indicate struts in the mesh that help to stabilize the Au interconnects after dissolution of the silk. The inset illustrates the high degree of conformal contact that can be achieved on the brain model once the silk substrate has been dissolved.

Figure 4. Mechanical modelling, theoretical predictions and measured properties

a, A thin film wrapped around a cylinder of radius R. The unwrapped and wrapped states appear in the top and center frames, respectively. The bottom frame compares the mechanics model and experiments. b, A thin film wrapped around two overlapped cylinders. The top and center frames show the unwrapped and wrapped states, respectively. The bottom frame shows a comparison between the mechanics model and experiments. c, Images of electrode arrays (76 μm sheet in left top, 2.5 μm sheet in right top and 2.5 μm mesh in bottom panel) wrapped onto a glass hemisphere. d, Mechanics models for sheet (left frame) and mesh (right frame) designs.

Figure 5. Photographs and data from animal validation experiments

Image of electrode array on feline brain (left) and average evoked response from each electrode (right) with the color showing the ratio of the RMS amplitude of each average electrode response in the 200 ms window (plotted) immediately after the presentation of the visual stimulus to the RMS amplitude of the average 1.5 second window (not shown) immediately preceding the stimulus presentation for 76 μm a, 2.5 μm b and 2.5 μm mesh c electrode array. The stimulus presentation occurs at the left edge of the plotted window. In all 3 images, the occipital pole is at the bottom of the frame and medial is at the right. The scale bars at the bottom of c indicate the spatial scale for the left frames and the voltage and time scales for the right frames of a,b and c. The color bar at the bottom of c provides the scale utilized in the right frames of a,b, and c to indicate the RMS amplitude ratios. d, Representative voltage data from a single electrode in a 2.5 μm mesh electrode array showing a sleep spindle.