Emerging Modalities and Implantable Technologies for Neuromodulation.

Techniques for neuromodulation serve as effective routes to care of patients with many types of challenging conditions. Continued progress in this field of medicine will require (1) improvements in our understanding of the mechanisms of neural control over organ function and (2) advances in technologies for precisely modulating these functions in a programmable manner. This review presents recent research on devices that are relevant to both of these goals, with an emphasis on multimodal operation, miniaturized dimensions, biocompatible designs, advanced neural interface schemes, and battery-free, wireless capabilities. A future that involves recording and modulating neural activity with such systems, including those that exploit closed-loop strategies and/or bioresorbable designs, seems increasingly within reach.

Transient, Implantable, Ultrathin Biofuel Cells Enabled by Laser-Induced Graphene and Gold Nanoparticles Composite.

Transient power sources with excellent biocompatibility and bioresorablility have attracted significant attention. Here, we report high-performance, transient glucose enzymatic biofuel cells (TEBFCs) based on the laser-induced graphene (LIG)/gold nanoparticles (Au NPs) composite electrodes. Such LIG electrodes can be easily fabricated from polyimide (PI) with an infrared CO2 laser and exhibit a low impedance (16 Ω). The resulted TEBFC yields a high open circuit potential (OCP) of 0.77 V and a maximum power density of 483.1 µW/cm2. The TEBFC not only exhibits a quick response time that enables reaching the maximum OCP within 1 min but also owns a long lifetime over 28 days in vitro. The excellent biocompatibility and transient performance from in vitro and in vivo tests allow long-term implantation of TEBFCs in rats for energy harvesting. The TEBFCs with advanced processing methods provide a promising power solution for transient electronics.

Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery.

A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.

Flexible electronic/optoelectronic microsystems with scalable designs for chronic biointegration.

Flexible biocompatible electronic systems that leverage key materials and manufacturing techniques associated with the consumer electronics industry have potential for broad applications in biomedicine and biological research. This study reports scalable approaches to technologies of this type, where thin microscale device components integrate onto flexible polymer substrates in interconnected arrays to provide multimodal, high performance operational capabilities as intimately coupled biointerfaces. Specificially, the material options and engineering schemes summarized here serve as foundations for diverse, heterogeneously integrated systems. Scaled examples incorporate >32,000 silicon microdie and inorganic microscale light-emitting diodes derived from wafer sources distributed at variable pitch spacings and fill factors across large areas on polymer films, at full organ-scale dimensions such as human brain, over ∼150 cm2 In vitro studies and accelerated testing in simulated biofluids, together with theoretical simulations of underlying processes, yield quantitative insights into the key materials aspects. The results suggest an ability of these systems to operate in a biologically safe, stable fashion with projected lifetimes of several decades without leakage currents or reductions in performance. The versatility of these combined concepts suggests applicability to many classes of biointegrated semiconductor devices.

Materials for flexible bioelectronic systems as chronic neural interfaces.

Engineered systems that can serve as chronically stable, high-performance electronic recording and stimulation interfaces to the brain and other parts of the nervous system, with cellular-level resolution across macroscopic areas, are of broad interest to the neuroscience and biomedical communities. Challenges remain in the development of biocompatible materials and the design of flexible implants for these purposes, where ulimate goals are for performance attributes approaching those of conventional wafer-based technologies and for operational timescales reaching the human lifespan. This Review summarizes recent advances in this field, with emphasis on active and passive constituent materials, design architectures and integration methods that support necessary levels of biocompatibility, electronic functionality, long-term stable operation in biofluids and reliability for use in vivo. Bioelectronic systems that enable multiplexed electrophysiological mapping across large areas at high spatiotemporal resolution are surveyed, with a particular focus on those with proven chronic stability in live animal models and scalability to thousands of channels over human-brain-scale dimensions. Research in materials science will continue to underpin progress in this field of study.

Conductively coupled flexible silicon electronic systems for chronic neural electrophysiology.

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.

Materials and processing approaches for foundry-compatible transient electronics.

Foundry-based routes to transient silicon electronic devices have the potential to serve as the manufacturing basis for "green" electronic devices, biodegradable implants, hardware secure data storage systems, and unrecoverable remote devices. This article introduces materials and processing approaches that enable state-of-the-art silicon complementary metal-oxide-semiconductor (CMOS) foundries to be leveraged for high-performance, water-soluble forms of electronics. The key elements are (i) collections of biodegradable electronic materials (e.g., silicon, tungsten, silicon nitride, silicon dioxide) and device architectures that are compatible with manufacturing procedures currently used in the integrated circuit industry, (ii) release schemes and transfer printing methods for integration of multiple ultrathin components formed in this way onto biodegradable polymer substrates, and (iii) planarization and metallization techniques to yield interconnected and fully functional systems. Various CMOS devices and circuit elements created in this fashion and detailed measurements of their electrical characteristics highlight the capabilities. Accelerated dissolution studies in aqueous environments reveal the chemical kinetics associated with the underlying transient behaviors. The results demonstrate the technical feasibility for using foundry-based routes to sophisticated forms of transient electronic devices, with functional capabilities and cost structures that could support diverse applications in the biomedical, military, industrial, and consumer industries.

Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems.

Materials that can serve as long-lived barriers to biofluids are essential to the development of any type of chronic electronic implant. Devices such as cardiac pacemakers and cochlear implants use bulk metal or ceramic packages as hermetic enclosures for the electronics. Emerging classes of flexible, biointegrated electronic systems demand similar levels of isolation from biofluids but with thin, compliant films that can simultaneously serve as biointerfaces for sensing and/or actuation while in contact with the soft, curved, and moving surfaces of target organs. This paper introduces a solution to this materials challenge that combines (i) ultrathin, pristine layers of silicon dioxide (SiO2) thermally grown on device-grade silicon wafers, and (ii) processing schemes that allow integration of these materials onto flexible electronic platforms. Accelerated lifetime tests suggest robust barrier characteristics on timescales that approach 70 y, in layers that are sufficiently thin (less than 1 µm) to avoid significant compromises in mechanical flexibility or in electrical interface fidelity. Detailed studies of temperature- and thickness-dependent electrical and physical properties reveal the key characteristics. Molecular simulations highlight essential aspects of the chemistry that governs interactions between the SiO2 and surrounding water. Examples of use with passive and active components in high-performance flexible electronic devices suggest broad utility in advanced chronic implants.

Flexible Transient Phototransistors by Use of Wafer-Compatible Transferred Silicon Nanomembranes.

Flexible transient photodetectors, a form of optoelectronic sensors that can be physically self-destroyed in a controllable manner, could be one of the important components for future transient electronic systems. In this work, a scalable, device-first, and bottom-up thinning process enables the fabrication of a flexible transient phototransistor on a wafer-compatible transferred silicon nanomembrane. A gate modulation significantly restrains the dark current to 10-12 A. With full exposure of the light-sensitive channel, such a device yields an ultrahigh photo-to-dark current ratio of 107 with a responsivity of 1.34 A W-1 (λ = 405 nm). The use of a high-temperature degradable polymer transient interlayer realizes on-demand self-destruction of the fabricated phototransistors, which offers a solution to the technical security issue of advanced flexible electronics. Such demonstration paves a new way for designing transient optoelectronic devices with a wafer-compatible process.

Schottky contact on ultra-thin silicon nanomembranes under light illumination.

By repeating oxidation and subsequent wet chemical etching, we produced ultra-thin silicon nanomembranes down to 10 nm based on silicon-on-insulator structures in a controllable way. The electrical property of such silicon nanomembranes is highly influenced by their contacts with metal electrodes, in which Schottky barriers (SBs) can be tuned by light illumination due to the surface doping. Thermionic emission theory of carriers is applied to estimate the SB at the interface between metal electrodes and Si nanomembranes. Our work reveals that the Schottky contacts with Si nanomembranes can be influenced by external stimuli (like light luminescence or surface state) more heavily compared to those in the thicker ones, which implies that such ultra-thin-film devices could be of potential use in optical detectors.

Anti-friction gold-based stretchable electronics enabled by interfacial diffusion-induced cohesion.

Stretchable electronics that prevalently adopt chemically inert metals as sensing layers and interconnect wires have enabled high-fidelity signal acquisition for on-skin applications. However, the weak interfacial interaction between inert metals and elastomers limit the tolerance of the device to external friction interferences. Here, we report an interfacial diffusion-induced cohesion strategy that utilizes hydrophilic polyurethane to wet gold (Au) grains and render them wrapped by strong hydrogen bonding, resulting in a high interfacial binding strength of 1017.6 N/m. By further constructing a nanoscale rough configuration of the polyurethane (RPU), the binding strength of Au-RPU device increases to 1243.4 N/m, which is 100 and 4 times higher than that of conventional polydimethylsiloxane and styrene-ethylene-butylene-styrene-based devices, respectively. The stretchable Au-RPU device can remain good electrical conductivity after 1022 frictions at 130 kPa pressure, and reliably record high-fidelity electrophysiological signals. Furthermore, an anti-friction pressure sensor array is constructed based on Au-RPU interconnect wires, demonstrating a superior mechanical durability for concentrated large pressure acquisition. This chemical modification-free approach of interfacial strengthening for chemically inert metal-based stretchable electronics is promising for three-dimensional integration and on-chip interconnection.

Multilevel design and construction in nanomembrane rolling for three-dimensional angle-sensitive photodetection.

Releasing pre-strained two-dimensional nanomembranes to assemble on-chip three-dimensional devices is crucial for upcoming advanced electronic and optoelectronic applications. However, the release process is affected by many unclear factors, hindering the transition from laboratory to industrial applications. Here, we propose a quasistatic multilevel finite element modeling to assemble three-dimensional structures from two-dimensional nanomembranes and offer verification results by various bilayer nanomembranes. Take Si/Cr nanomembrane as an example, we confirm that the three-dimensional structural formation is governed by both the minimum energy state and the geometric constraints imposed by the edges of the sacrificial layer. Large-scale, high-yield fabrication of three-dimensional structures is achieved, and two distinct three-dimensional structures are assembled from the same precursor. Six types of three-dimensional Si/Cr photodetectors are then prepared to resolve the incident angle of light with a deep neural network model, opening up possibilities for the design and manufacturing methods of More-than-Moore-era devices.

Ultrathin, Transferred Layers of Silicon Oxynitrides as Tunable Biofluid Barriers for Bioresorbable Electronic Systems.

Bio/ecoresorbable electronic systems create unique opportunities in implantable medical devices that serve a need over a finite time period and then disappear naturally to eliminate the need for extraction surgeries. A critical challenge in the development of this type of technology is in materials that can serve as thin, stable barriers to surrounding ground water or biofluids, yet ultimately dissolve completely to benign end products. This paper describes a class of inorganic material (silicon oxynitride, SiON) that can be formed in thin films by plasma-enhanced chemical vapor deposition for this purpose. In vitro studies suggest that SiON and its dissolution products are biocompatible, indicating the potential for its use in implantable devices. A facile process to fabricate flexible, wafer-scale multilayer films bypasses limitations associated with the mechanical fragility of inorganic thin films. Systematic computational, analytical, and experimental studies highlight the essential materials aspects. Demonstrations in wireless light-emitting diodes both in vitro and in vivo illustrate the practical use of these materials strategies. The ability to select degradation rates and water permeability through fine tuning of chemical compositions and thicknesses provides the opportunity to obtain a range of functional lifetimes to meet different application requirements.

One-step rolling fabrication of VO2 tubular bolometers with polarization-sensitive and omnidirectional detection.

Uncooled infrared detection based on vanadium dioxide (VO2) radiometer is highly demanded in temperature monitoring and security protection. The key to its breakthrough is to fabricate bolometer arrays with great absorbance and excellent thermal insulation using a straightforward procedure. Here, we show a tubular bolometer by one-step rolling VO2 nanomembranes with enhanced infrared detection. The tubular geometry enhances the thermal insulation, light absorption, and temperature sensitivity of freestanding VO2 nanomembranes. This tubular VO2 bolometer exhibits a detectivity of ~2 × 108 cm Hz1/2 W-1 in the ultrabroad infrared spectrum, a response time of ~2.0 ms, and a calculated noise-equivalent temperature difference of 64.5 mK. Furthermore, our device presents a workable structural paradigm for polarization-sensitive and omnidirectional light coupling bolometers. The demonstrated overall characteristics suggest that tubular bolometers have the potential to narrow performance and cost gap between photon detectors and thermal detectors with low cost and broad applications.

Self-Rolled-Up Ultrathin Single-Crystalline Silicon Nanomembranes for On-Chip Tubular Polarization Photodetectors.

Freestanding single-crystalline nanomembranes and their assembly have broad application potential in photodetectors for integrated chips. However, the release and self-assembly process of single-crystalline semiconductor nanomembranes still remains a great challenge in on-chip processing and functional integration, and photodetectors based on nanomembrane always suffer from limited absorption of nanoscale thickness. Here, a non-destructive releasing and rolling process is employed to prepare tubular photodetectors based on freestanding single-crystalline Si nanomembranes. Spontaneous release and self-assembly are achieved by residual strain introduced by lattice mismatch at the epitaxial interface of Si and Ge, and the intrinsic stress and strain distributions in self-rolled-up Si nanomembranes are analyzed experimentally and computationally. The advantages of light trapping and wide-angle optical coupling are realized by tubular geometry. This Si microtube device achieves reliable Ohmic contact and exhibits a photoresponsivity of over 330 mA W-1 , a response time of 370 µs, and a light incident detection angle range of over 120°. Furthermore, the microtubular structure shows a distinct polarization angle-dependent light absorption, with a dichroic ratio of 1.24 achieved at 940 nm. The proposed Si-based microtubes provide new possibilities for the construction of multifunctional chips for integrated circuit ecosystems in the More than Moore era.

Ultrathin, Soft, Bioresorbable Organic Electrochemical Transistors for Transient Spatiotemporal Mapping of Brain Activity.

A critical challenge lies in the development of the next-generation neural interface, in mechanically tissue-compatible fashion, that offer accurate, transient recording electrophysiological (EP) information and autonomous degradation after stable operation. Here, an ultrathin, lightweight, soft and multichannel neural interface is presented based on organic-electrochemical-transistor-(OECT)-based network, with capabilities of continuous high-fidelity mapping of neural signals and biosafety active degrading after performing functions. Such platform yields a high spatiotemporal resolution of 1.42 ms and 20 µm, with signal-to-noise ratio up to ≈37 dB. The implantable OECT arrays can well establish stable functional neural interfaces, designed as fully biodegradable electronic platforms in vivo. Demonstrated applications of such OECT implants include real-time monitoring of electrical activities from the cortical surface of rats under various conditions (e.g., narcosis, epileptic seizure, and electric stimuli) and electrocorticography mapping from 100 channels. This technology offers general applicability in neural interfaces, with great potential utility in treatment/diagnosis of neurological disorders.

Recent advances in microsystem approaches for mechanical characterization of soft biological tissues.

Microsystem technologies for evaluating the mechanical properties of soft biological tissues offer various capabilities relevant to medical research and clinical diagnosis of pathophysiologic conditions. Recent progress includes (1) the development of tissue-compliant designs that provide minimally invasive interfaces to soft, dynamic biological surfaces and (2) improvements in options for assessments of elastic moduli at spatial scales from cellular resolution to macroscopic areas and across depths from superficial levels to deep geometries. This review summarizes a collection of these technologies, with an emphasis on operational principles, fabrication methods, device designs, integration schemes, and measurement features. The core content begins with a discussion of platforms ranging from penetrating filamentary probes and shape-conformal sheets to stretchable arrays of ultrasonic transducers. Subsequent sections examine different techniques based on planar microelectromechanical system (MEMS) approaches for biocompatible interfaces to targets that span scales from individual cells to organs. One highlighted example includes miniature electromechanical devices that allow depth profiling of soft tissue biomechanics across a wide range of thicknesses. The clinical utility of these technologies is in monitoring changes in tissue properties and in targeting/identifying diseased tissues with distinct variations in modulus. The results suggest future opportunities in engineered systems for biomechanical sensing, spanning a broad scope of applications with relevance to many aspects of health care and biology research.

Nanomembrane-assembled nanophotonics and optoelectronics: from materials to applications.

Nanophotonics and optoelectronics are the keys to the information transmission technology field. The performance of the devices crucially depends on the light-matter interaction, and it is found that three-dimensional (3D) structures may be associated with strong light field regulation for advantageous application. Recently, 3D assembly of flexible nanomembranes has attracted increasing attention in optical field, and novel optoelectronic device applications have been demonstrated with fantastic 3D design. In this review, we first introduce the fabrication of various materials in the form of nanomembranes. On the basis of the deformability of nanomembranes, 3D structures can be built by patterning and release steps. Specifically, assembly methods to build 3D nanomembrane are summarized as rolling, folding, buckling and pick-place methods. Incorporating functional materials and constructing fine structures are two important development directions in 3D nanophotonics and optoelectronics, and we settle previous researches on these two aspects. The extraordinary performance and applicability of 3D devices show the potential of nanomembrane assembly for future optoelectronic applications in multiple areas.

Self-rolling of vanadium dioxide nanomembranes for enhanced multi-level solar modulation.

Thermochromic window develops as a competitive solution for carbon emissions due to comprehensive advantages of its passivity and effective utilization of energy. How to further enhance the solar modulation ([Formula: see text]) of thermochromic windows while ensuring high luminous transmittance ([Formula: see text]) becomes the latest challenge to touch the limit of energy efficiency. Here, we show a smart window combining mechanochromism with thermochromism by self-rolling of vanadium dioxide (VO2) nanomembranes to enhance multi-level solar modulation. The mechanochromism is introduced by the temperature-controlled regulation of curvature of rolled-up smart window, which benefits from effective strain adjustment in VO2 nanomembranes upon the phase transition. Under geometry design and optimization, the rolled-up smart window with high [Formula: see text] and [Formula: see text] is achieved for the modulation of indoor temperature self-adapted to seasons and climate. Furthermore, such rolled-up smart window enables high infrared reflectance after triggered phase transition and acts as a smart lens protective cover for strong radiation. This work supports the feasibility of self-rolling technology in smart windows and lens protection, which promises broad interest and practical applications of self-adapting devices and systems for smart building, intelligent sensors and actuators with the perspective of energy efficiency.

Mapping of Spatiotemporal Auricular Electrophysiological Signals Reveals Human Biometric Clusters.

Underneath the ear skin there are rich vascular network and sensory nerve branches. Hence, the 3D mapping of auricular electrophysiological signals can provide new biomedical perspectives. However, it is still extremely challenging for current sensing techniques to cover the entire ultra-curved auricle. Here, a 3D graphene-based ear-conformable sensing device with embedded and distributed 3D electrodes for full-auricle physiological monitoring is reported. As a proof-of-concept, spatiotemporal auricular electrical skin resistance (AESR) mapping is demonstrated for the first time, and human subject-specific AESR distributions are observed. From the data of more than 30 ears (both right and left ears), the auricular region-specific AESR changes after cycling exercise are observed in 98% of the tests and are clustered into four groups via machine learning-based data analyses. Correlations of AESR with heart rate and blood pressure are also studied. This 3D electronic platform and AESR-based biometrical findings show promising biomedical applications.