Syringe-injectable electronics

Abstract

Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.

Figure 1. Syringe injectable electronics

a to c, Schematics of injectable electronics. The red-orange lines highlight the overall mesh structure and indicate the regions of supporting and passivating polymer mesh layers; the yellow lines indicate metal interconnects between I/O pads (green filled circles) and recording devices (blue filled circles). d, Schematic of the mesh electronics design (upper image), where the orange and red lines represent polymer encapsulated metal interconnects and supporting polymer elements, respectively, and W is the total width of the mesh. The dashed black box (lower image) highlights the structure of one unit cell (white dashed lines), where α is the angle deviation from rectangular. e, Longitudinal mesh bending stiffness, D_L, and transverse mesh bending stiffness, D_T, as a function of α defined in d. f and g, Images of mesh electronics injection through a glass needle, ID = 95 μm, into 1x PBS solution. Bright-field microscopy image f of the mesh electronics immediately prior to injection into solution; the red arrow indicates the end of the mesh inside the glass needle. 3D reconstructed confocal fluorescence image g recorded following injection of ca. 0.5 cm mesh electronics into 1x PBS solution. The blue and white dashed boxes correspond to regions shown in Supplementary Fig. 3a and b. h, Optical image of an injectable mesh electronics structure unfolded on a glass substrate. W is the total width of the mesh electronics. The red dashed polygon highlights the position of electrochemical devices or FET devices. Green and black dashed boxes highlighted metal interconnect lines and metal I/O pads, respectively. i and j, Yields and change with ±1 standard deviation (±1SD) in properties post-injection for single-terminal electrochemical and two-terminal field-effect transistor (FET) devices. i, Yield (blue) and impedance change (red) of the metal electrodes from the mesh electronics injected through 32, 26 and 22 gauge metal needles. Inset: bright field image of a representative metal electrode on mesh electronics, where the sensing electrode is highlighted by a red arrow. Scale Bar: 20 μm. j, Yield (blue) and conductance change (red) of silicon nanowire FETs following injection through 32, 26, 24, 22 and 20 gauge needles. Inset: scanning electron microscopy (SEM) image of a representative nanowire FET device in the mesh electronics; the nanowire is highlighted by the red arrow. Scale bar: 2 μm.

Figure 2. Imaging mesh electronics structure in needle constrictions

a, Schematic illustrating the structure of a pulled glass tube (blue) with mesh electronics passing from larger (left) to smallest (center) ID of tube, where the red arrow indicates the direction of injection and x-y-z axes indicate coordinates relative to the microscope objective for images in c to e. b, Schematic image of the mesh structure from the region of the constriction indicated by the blue dashed box in a. c, Bright-field microscopy images of different design mesh electronics injected through glass channels. I and II, total width, W = 5 mm, α = 45° mesh electronics injected through 450 and 250 μm ID, respectively, glass channels. III, W = 15 mm, α = 45° mesh electronics injected through a 450 μm ID glass channel. IV, W = 10 mm, α = 0° mesh electronics injected through a 450 μm ID glass channel. The injection direction is indicated by red arrows in the images; the orientation relative to the axes in a are indicated in I and the same for panels I to IV. d, 3D reconstructed confocal images from the dashed red box regions in the respective panels I to IV in c; the x-y-z axes in I are the same for panels II to IV. Horizontal, small white arrows in c and d indicate several of the longitudinal elements containing metal interconnects in the mesh electronics. e, Cross-sectional images plotted as half cylinders from positions indicated by the vertical white dashed lines in d. The white dashed curves indicate the approximate IDs of the glass constrictions.

Figure 3. Syringe injection of mesh electronics into 3D synthetic structures

a, Schematic of a mesh electronics injected with uncured PDMS precursor into a PDMS cavity (blue) with I/O pads unfolded outside the cavity. The injected PDMS precursors were cured after injection. The red lines highlight the overall mesh structure and indicate the regions of supporting and passivating polymers and the yellow lines indicate the metal interconnects between I/O pads (yellow filled circle) and devices (dark blue filled circle). b, μCT image shows the zoomed-in structure highlighted by the black dashed box in a and Supplementary Fig. 7b. False colors were applied with metal lines (yellow) in PDMS (purple). c, 4 nanowire devices response to pressure applied on the PDMS. The blue downward and upward pointing triangles denote the times when the strain was applied and released, respectively. The purple downward and upward arrows show the tensile and compressive strains, corresponding to the minus and plus change of conductance, respectively. d to f, (upper images) 3D reconstructed μCT images of a mesh electronics injected into 75% Matrigel™ after incubating for 0 h d, 24 h e, and 3 weeks f at 37 °C. The x-y-z axes are shown in d and the same for panels e and f, where the injection direction is ca. along the z-axis. In d to f, false colors were applied with metal lines in the mesh (yellow) and the Matrigel™ (purple) (lower images). Corresponding cross-section images at z = 10 mm with 500 μm thicknesses; the positions of the cross-sections are indicated by white dashed lines in the upper images. The maximum extent of mesh electronics unfolding was highlighted by white dashed circles with diameter, D, in each image. g, Time dependence of mesh electronics unfolding following injection into 25% (black), 75% (red) and 100% (blue) Matrigel™; the measured diameter, D, was normalized by the 2D width, W, of the fabricated mesh electronics. D was sampled from five cross-sections taken at z =5, 7.5, 10, 12.5 and 15 mm to obtain the average ± 1SD.

Figure 4. Syringe injectable electronics into in vivo biological system

a, Schematic shows in vivo stereotaxic injection of mesh electronics into a mouse brain. b, Optical image of the stereotaxic injection of mesh electronics into an anesthetized 3 months old mouse brain. c and d, Schematics of coronal slices illustrating the two distinct areas of the brain that mesh electronics were injected: c, through the cerebral cortex (CTX) into the lateral ventricle (LV) cavity adjacent to the caudoputamen (CPu) and lateral septal nucleus (LSD), and d, through the CTX into the hippocampus (HIP). Red lines highlight and indicate the overall structure of mesh and dark blue filled circles indicate recording devices. The blue dashed line in c indicates the direction of horizontal slicing for imaging. e, Projection of 3D reconstructed confocal image from 100 μm thick, 3.17 mm long and 3.17 mm wide volume horizontal slice 5 weeks post-injection at the position indicated by blue dashed line in c. Red dashed line highlights the boundary of mesh inside LV, and the solid red circle indicates the size of the needle used for injection. The red, green and blue colors in this correspond to GFAP, NeuN/SU-8 and DAPI, respectively, and are denoted at the top of the image panel in this and subsequent images. f, 3D reconstructed confocal image from the dashed red box in Supplementary Fig. 8a at the interface between mesh electronics and subventricular zone (SVZ). g, 3D reconstructed confocal image from dashed red box in Supplementary Fig. 8c at the ca. middle (of x-y plane) of the LV in the slice. h, Bright-field microscopy image of a coronal slice of the HIP region 5 weeks post-injection of the mesh electronics at the position indicated in schematic d. Red dashed lines indicate the boundary of the glass needle. The white arrows indicate longitudinal elements that were broken during tissue slicing. Black dashed lines indicate the boundary of each individual image. i, Overlaid bright field and epi-fluorescence images from the region indicated by white dashed box in h. Blue corresponds to DAPI staining of cell nuclei, white arrows indicate CA1 and dentate gyrus (DG) of the HIP. j, Projection of 3D reconstructed confocal image from 30 μm thick, 317 μm long and 317 μm wide volume from the zoomed-in region highlighted by the black dashed box in i. k, Acute in vivo 16-channel recording using mesh electronics injected into a mouse brain. The devices were Pt-metal electrodes (impedance ~950 kΩ at 1 kHz) with their relative positions marked by red spots in the schematic (left panel), and the signal was filtered with 60 Hz notch during acquisition. The dashed red rectangle indicates the part for spatiotemporal mapping of multichannel-LFP recordings (Supplementary Fig. 12d) l, Superimposed single-unit neural recordings from one channel after 300-6000 Hz band-pass filtering. The red line represents the mean waveform for the single-unit spikes.