Materials and Structural Designs toward Motion Artifact-Free Bioelectronics.

Bioelectronics encompassing electronic components and circuits for accessing human information play a vital role in real-time and continuous monitoring of biophysiological signals of electrophysiology, mechanical physiology, and electrochemical physiology. However, mechanical noise, particularly motion artifacts, poses a significant challenge in accurately detecting and analyzing target signals. While software-based "postprocessing" methods and signal filtering techniques have been widely employed, challenges such as signal distortion, major requirement of accurate models for classification, power consumption, and data delay inevitably persist. This review presents an overview of noise reduction strategies in bioelectronics, focusing on reducing motion artifacts and improving the signal-to-noise ratio through hardware-based approaches such as "preprocessing". One of the main stress-avoiding strategies is reducing elastic mechanical energies applied to bioelectronics to prevent stress-induced motion artifacts. Various approaches including strain-compliance, strain-resistance, and stress-damping techniques using unique materials and structures have been explored. Future research should optimize materials and structure designs, establish stable processes and measurement methods, and develop techniques for selectively separating and processing overlapping noises. Ultimately, these advancements will contribute to the development of more reliable and effective bioelectronics for healthcare monitoring and diagnostics.

Wearable and Implantable Cortisol-Sensing Electronics for Stress Monitoring.

Cortisol is a steroid hormone that is released from the body in response to stress. Although a moderate level of cortisol secretion can help the body maintain homeostasis, excessive secretion can cause various diseases, such as depression and anxiety. Conventional methods for cortisol measurement undergo procedures that limit continuous monitoring, typically collecting samples of bodily fluids, followed by separate analysis in a laboratory setting that takes several hours. Thus, recent studies demonstrate wearable, miniaturized sensors integrated with electronic modules that enable wireless real-time analysis. Here, the primary focus is on wearable and implantable electronic devices that continuously measure cortisol concentration. Diverse types of cortisol-sensing techniques, such as antibody-, DNA-aptamer-, and molecularly imprinted polymer-based sensors, as well as wearable and implantable devices that aim to continuously monitor cortisol in a minimally invasive fashion are discussed. In addition to the cortisol monitors that directly measure stress levels, other schemes that indirectly measure stress, such as electrophysiological signals and sweat are also summarized. Finally, the challenges and future directions in stress monitoring and management electronics are reviewed.

Stretchable and Directly Patternable Double-Layer Structure Electrodes with Complete Coverage.

Stretchable electrodes are widely used in next-generation wearable electronics. Recent studies incorporated designs that help rigid electrodes attain stretchability. However, these structures exhibited unsatisfactory charge/signal extraction efficiency because of their low areal fill factor. Additionally, they cannot be photolithographically patterned on polymer substrates because of their low adhesion, requiring additional complicated fabrication steps. We developed photolithographically patternable stretchable electrodes with complete coverage and enhanced charge-extraction efficiency. The electrodes, comprising double layers, included a chemically treated Ag nanowire mesh and Au thin film. The interfacial linker role of polyvinylpyrrolidone chemically strengthened the interfacial bonds, and the reinforced concrete structure of nanowire-embedded metal thin films enhanced the mechanical properties. Therefore, the electrodes provided superior efficiency and stability in capturing physical, electromagnetic, and electrophysiological signals while exceeding the existing stretchable electrode limits. A broad range of applications are foreseen, such as electrocardiogram sensing electrodes, strain sensors, temperature sensors, and antennas.

Cuticular pad-inspired selective frequency damper for nearly dynamic noise-free bioelectronics.

Bioelectronics needs to continuously monitor mechanical and electrophysiological signals for patients. However, the signals always include artifacts by patients' unexpected movement (such as walking and respiration under approximately 30 hertz). The current method to remove them is a signal process that uses a bandpass filter, which may cause signal loss. We present an unconventional bandpass filter material-viscoelastic gelatin-chitosan hydrogel damper, inspired by the viscoelastic cuticular pad in a spider-to remove dynamic mechanical noise artifacts selectively. The hydrogel exhibits frequency-dependent phase transition that results in a rubbery state that damps low-frequency noise and a glassy state that transmits the desired high-frequency signals. It serves as an adaptable passfilter that enables the acquisition of high-quality signals from patients while minimizing signal process for advanced bioelectronics.

High-Performance Implantable Bioelectrodes with Immunocompatible Topography for Modulation of Macrophage Responses.

Implantable bioelectrodes enable precise recording or stimulation of electrical signals with living tissues in close contact. However, their performance is frequently compromised owing to inflammatory tissue reactions, which macrophages either induce or resolve by polarizing to an inflammatory (M1) or noninflammatory (M2) phenotype, respectively. Thus, we aimed to fabricate biocompatible and functional implantable conductive polymer bioelectrodes with optimal topography for the modulation of macrophage responses. To this end, we produced heparin-doped polypyrrole (PPy/Hep) electrodes of different surface roughness, with Ra values from 5.5 to 17.6 nm, by varying the charge densities during electrochemical synthesis. In vitro culture revealed that macrophages on rough PPy/Hep electrodes preferentially polarized to noninflammatory phenotypes. In particular, PPy/Hep-900 (Ra = 14 nm) was optimal with respect to electrochemical properties and the suppression of inflammatory M1 polarization. In vivo implantation indicated that PPy/Hep-900 significantly reduced macrophage recruitment, suppressed inflammatory polarization, and mitigated fibrotic tissue formation. In addition, the implanted PPy/Hep-900 electrodes could successfully record electrocardiographic signals for up to 10 days without substantial decreases in sensitivity, while other electrodes substantially lost their signal sensitivity during implantation. Altogether, we demonstrate that modulating the surface features of PPy/Hep can benefit the design and applications of high-performance and high-biocompatibility bioelectrodes.

Cerebrospinal Fluid-philic and Biocompatibility-Enhanced Soft Cranial Window for Long-Term In Vivo Brain Imaging.

Soft, transparent poly(dimethyl siloxane) (PDMS)-based cranial windows in animal models have created many opportunities to investigate brain functions with multiple in vivo imaging modalities. However, due to the hydrophobic nature of PDMS, the wettability by cerebrospinal fluid (CSF) is poor, which may cause air bubble trapping beneath the window during implantation surgery, and favorable heterogeneous bubble nucleation at the interface between hydrophobic PDMS and CSF. This may result in excessive growth of the entrapped bubble under the soft cranial window. Herein, to yield biocompatibility-enhanced, trapped bubble-minimized, and soft cranial windows, this report introduces a CSF-philic PDMS window coated with hydroxyl-enriched poly(vinyl alcohol) (PVA) for long-term in vivo imaging. The PVA-coated PDMS (PVA/PDMS) film exhibits a low contact angle θACA (33.7 ± 1.9°) with artificial CSF solution and maintains sustained CSF-philicity. The presence of the PVA layer achieves air bubble-free implantation of the soft cranial window, as well as induces the formation of a thin wetting film that shows anti-biofouling performance through abundant water molecules on the surface, leading to long-term optical clarity. In vivo studies on the mice cortex verify that the soft and CSF-philic features of the PVA/PDMS film provide minimal damage to neuronal tissues and attenuate immune response. These advantages of the PVA/PDMS window are strongly correlated with the enhancement of cortical hemodynamic changes and the local field potential recorded through the PVA/PDMS film, respectively. This collection of results demonstrates the potential for future microfluidic platforms for minimally invasive CSF extraction utilizing a CSF-philic fluidic passage.

Injectable Biomedical Devices for Sensing and Stimulating Internal Body Organs.

The rapid pace of progress in implantable electronics driven by novel technology has created devices with unconventional designs and features to reduce invasiveness and establish new sensing and stimulating techniques. Among the designs, injectable forms of biomedical electronics are explored for accurate and safe targeting of deep-seated body organs. Here, the classes of biomedical electronics and tools that have high aspect ratio structures designed to be injected or inserted into internal organs for minimally invasive monitoring and therapy are reviewed. Compared with devices in bulky or planar formats, the long shaft-like forms of implantable devices are easily placed in the organs with minimized outward protrusions via injection or insertion processes. Adding flexibility to the devices also enables effortless insertions through complex biological cavities, such as the cochlea, and enhances chronic reliability by complying with natural body movements, such as the heartbeat. Diverse types of such injectable implants developed for different organs are reviewed and the electronic, optoelectronic, piezoelectric, and microfluidic devices that enable stimulations and measurements of site-specific regions in the body are discussed. Noninvasive penetration strategies to deliver the miniscule devices are also considered. Finally, the challenges and future directions associated with deep body biomedical electronics are explained.