Brain implantation of tissue-level-soft bioelectronics via embryonic development.

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

3D spatiotemporally scalable in vivo neural probes based on fluorinated elastomers.

Electronic devices for recording neural activity in the nervous system need to be scalable across large spatial and temporal scales while also providing millisecond and single-cell spatiotemporal resolution. However, existing high-resolution neural recording devices cannot achieve simultaneous scalability on both spatial and temporal levels due to a trade-off between sensor density and mechanical flexibility. Here we introduce a three-dimensional (3D) stacking implantable electronic platform, based on perfluorinated dielectric elastomers and tissue-level soft multilayer electrodes, that enables spatiotemporally scalable single-cell neural electrophysiology in the nervous system. Our elastomers exhibit stable dielectric performance for over a year in physiological solutions and are 10,000 times softer than conventional plastic dielectrics. By leveraging these unique characteristics we develop the packaging of lithographed nanometre-thick electrode arrays in a 3D configuration with a cross-sectional density of 7.6 electrodes per 100 µm2. The resulting 3D integrated multilayer soft electrode array retains tissue-level flexibility, reducing chronic immune responses in mouse neural tissues, and demonstrates the ability to reliably track electrical activity in the mouse brain or spinal cord over months without disrupting animal behaviour.

Pure Conducting Polymer Hydrogels Increase Signal-to-Noise of Cutaneous Electrodes by Lowering Skin Interface Impedance.

Cutaneous electrodes are routinely used for noninvasive electrophysiological sensing of signals from the brain, the heart, and the neuromuscular system. These bioelectronic signals propagate as ionic charge from their sources to the skin-electrode interface where they are then sensed as electronic charge by the instrumentation. However, these signals suffer from low signal-to-noise ratio arising from the high impedance at the tissue-to-electrode contact interface. This paper reports that soft conductive polymer hydrogels made purely of poly(3,4-ethylenedioxy-thiophene) doped with poly(styrene sulfonate) present nearly an order of magnitude decrease in the skin-electrode contact impedance (88%, 82%, and 77% at 10, 100, and 1 kHz, respectively) when compared to clinical electrodes in an ex vivo model that isolates the bioelectrochemical features of a single skin-electrode contact. Integrating these pure soft conductive polymer blocks into an adhesive wearable sensor enables high fidelity bioelectronic signals with higher signal-to-noise ratio (average 2.1 dB increase, max 3.4 dB increase) when compared to clinical electrodes across all subjects. The utility of these electrodes is demonstrated in a neural interface application. The conductive polymer hydrogels enable electromyogram-based velocity control of a robotic arm to complete a pick and place task. This work provides a basis for the characterization and use of conductive polymer hydrogels to better couple human and machine.

Stretchable Mesh Nanoelectronics for 3D Single-Cell Chronic Electrophysiology from Developing Brain Organoids.

Human induced pluripotent stem cell derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution of the electrical properties of brain organoids during development is currently limited by the measurement techniques, which cannot provide long-term stable 3D bioelectrical interfaces with developing brain organoids. Here, a cyborg brain organoid platform is reported, in which "tissue-like" stretchable mesh nanoelectronics are designed to match the mechanical properties of brain organoids and to be folded by the organogenetic process of progenitor or stem cells, distributing stretchable electrode arrays across the 3D organoids. The tissue-wide integrated stretchable electrode arrays show no interruption to brain organoid development, adapt to the volume and morphological changes during brain organoid organogenesis, and provide long-term stable electrical contacts with neurons within brain organoids during development. The seamless and noninvasive coupling of electrodes to neurons enables long-term stable, continuous recording and captures the emergence of single-cell action potentials from early-stage brain organoid development.

Stretchable Electrets: Nanoparticle-Elastomer Composites.

Manipulating charges is fundamental to numerous systems, and this ability is achieved through materials of diverse characteristics. Electrets are dielectrics that trap charges or dipoles. Applications include electrophotography, microphones, air filters, and energy harvesters. To trap charges or dipoles for a long time, electrets are commonly made of hard dielectrics. Stretchable dielectrics are short-lived electrets. The two properties, longevity and stretchability, conflict; existing electrets struggle to attain both. This work describes an approach to developing stretchable electrets. Nanoparticles of a hard electret are immobilized in a matrix of dielectric elastomer. The composite divides the labor of two functions: the particles trap charges with longevity, and the matrix enables stretchability. The design considerably broadens the choice of materials to enable stretchable electrets. Silica nanoparticles in the polydimethylsiloxane elastomer achieve a charge density ∼ 4 × 10-5 C m-2 and a lifetime beyond 60 days. Long-lived, stretchable electrets open extensive opportunities.

Fundamental Limits to the Electrochemical Impedance Stability of Dielectric Elastomers in Bioelectronics.

Incorporation of elastomers into bioelectronics that reduces the mechanical mismatch between electronics and biological systems could potentially improve the long-term electronics-tissue interface. However, the chronic stability of elastomers in physiological conditions has not been systematically studied. Here, using electrochemical impedance spectrum we find that the electrochemical impedance of dielectric elastomers degrades over time in physiological environments. Both experimental and computational results reveal that this phenomenon is due to the diffusion of ions from the physiological solution into elastomers over time. Their conductivity increases by 6 orders of magnitude up to 10-8 S/m. When the passivated conductors are also composed of intrinsically stretchable materials, higher leakage currents can be detected. Scaling analyses suggest fundamental limitations to the electrical performances of interconnects made of stretchable materials.

Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology.

Tissue-wide electrophysiology with single-cell and millisecond spatiotemporal resolution is critical for heart and brain studies. Issues arise, however, from the invasive, localized implantation of electronics that destroys well-connected cellular networks within matured organs. Here, we report the creation of cyborg organoids: the three-dimensional (3D) assembly of soft, stretchable mesh nanoelectronics across the entire organoid by the cell-cell attraction forces from 2D-to-3D tissue reconfiguration during organogenesis. We demonstrate that stretchable mesh nanoelectronics can migrate with and grow into the initial 2D cell layers to form the 3D organoid structure with minimal impact on tissue growth and differentiation. The intimate contact between the dispersed nanoelectronics and cells enables us to chronically and systematically observe the evolution, propagation, and synchronization of the bursting dynamics in human cardiac organoids through their entire organogenesis.

Stretchable materials of high toughness and low hysteresis.

In materials of all types, hysteresis and toughness are usually correlated. For example, a highly stretchable elastomer or hydrogel of a single polymer network has low hysteresis and low toughness. The single network is commonly toughened by introducing sacrificial bonds, but breaking and possibly reforming the sacrificial bonds causes pronounced hysteresis. In this paper, we describe a principle of stretchable materials that disrupt the toughness-hysteresis correlation, achieving both high toughness and low hysteresis. We demonstrate the principle by fabricating a composite of two constituents: a matrix of low elastic modulus, and fibers of high elastic modulus, with strong adhesion between the matrix and the fibers, but with no sacrificial bonds. Both constituents have low hysteresis (5%) and low toughness (300 J/m2), whereas the composite retains the low hysteresis but achieves high toughness (10,000 J/m2). Both constituents are prone to fatigue fracture, whereas the composite is highly fatigue resistant. We conduct experiment and computation to ascertain that the large modulus contrast alleviates stress concentration at the crack front, and that strong adhesion binds the fibers and the matrix and suppresses sliding between them. Stretchable materials of high toughness and low hysteresis provide opportunities to the creation of high-cycle and low-dissipation soft robots and soft human-machine interfaces.

Stretchable Seal.

Many stretchable electronic devices require stretchable hermetic seals. However, stretchability and permeability are inextricably linked at the molecular level: stretchable, low-permeability materials do not exist. We collect data for the permeation of water and oxygen in many materials and describe the scaling relations for both flat and wrinkled seals. Whereas flat seals struggle to fulfill the simultaneous requirements of stretchability, low stiffness, and low transmissibility, wrinkled seals can fulfill them readily. We further explore the behavior of wrinkled seals under cyclic stretch using aluminum, polyethylene, and silica films on elastomer substrates. The wrinkled aluminum develops fatigue cracks after a small number of cycles, but the wrinkled polyethylene and silica maintain low transmissibility after 10 000 cycles of tensile strain.

Wearable and Washable Conductors for Active Textiles.

The emergence of stretchable electronics and its potential integration with textiles have highlighted a challenge: Textiles are wearable and washable, but electronic devices are not. Many stretchable conductors have been developed to enable wearable active textiles, but little has been done to make them washable. Here we demonstrate a new class of stretchable conductors that can endure wearing and washing conditions commonly associated with textiles. Such a conductor consists of a hydrogel, a dissolved hygroscopic salt, and a butyl rubber coating. The hygroscopic salt enables ionic conduction and matches the relative humidity of the hydrogel to the average ambient relative humidity. The butyl rubber coating prevents the loss and gain of water due to the daily fluctuation of ambient relative humidity. We develop the chemistry of dip-coating the butyl rubber onto the hydrogel, using silanes to achieve both the cross-link of the butyl rubber and the adhesion between the butyl rubber and the hydrogel. We test the endurance of the conductor by soaking it in detergent while stretching it cyclically and by machine-washing it. The loss of water and salt is minimal. It is hoped that these conductors open applications in healthcare, entertainment, and fashion.