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Biosensors and bioelectronics (B&B) are typical devices working at the interfaces of biology and electronics [...].
Wearable and implantable bioelectronics enable continuous physiological monitoring and therapeutic modulation, yet their performance critically depends on the stability and conformality of the interfaces with soft and dynamic biological tissues. Mechanical and biochemical mismatches between conventional electronic materials and living tissues often lead to interfacial stress, unstable contact, and inflammatory responses that compromise the long-term function of bioelectronics. This review presents a mechanism-driven framework for understanding tissue-bioelectronics interfaces by systematically examining the physical, chemical, and biological interactions that govern device-tissue coupling across temporal and length scales. We show how these interfacial mechanisms inform key design principles in structural engineering and materials development, enabling improved mechanical compliance, adhesion, and long-term interfacial stability. We further highlight recent advances in fabrication strategies that support soft, conformal, and multifunctional bioelectronic systems, together with representative applications spanning physiological sensing and therapeutic modulation. Finally, we discuss emerging strategies for mitigating foreign-body responses and outline remaining challenges and opportunities for achieving durable, adaptive, and clinically translatable tissue-bioelectronics interfaces.
Long-chain aldehydes, particularly nonanal, are recognized as potential volatile biomarkers of lung cancer in exhaled breath. This study investigates the influence of peptide counter-ions on the performance of QCM-based biosensors using two odorant-binding protein-derived peptides (OBPP4 and OBPP4 GSGSGS) for the selective gas-phase detection of these aldehydes. Exchanging the counter-ion from trifluoroacetate to chloride improves biosensor sensitivity and lowers the limit of detection within the set of biosensors investigated in this study. The OBPP4 GSGSGS with chloride exhibited the highest sensitivity to nonanal (0.153 Hz/ppm) and the lowest LOD (9.8 ppm), with excellent selectivity over other groups of volatiles. The novelty of this work lies in demonstrating, for the first time, that simple counter-ion exchange in synthetic peptides can significantly enhance the gas-phase binding of volatile aldehydes, classified as lung cancer biomarkers, without altering the peptide sequence, offering a straightforward and effective optimization strategy for peptide-based piezoelectric biosensors.
Printed electronics have emerged as a versatile manufacturing platform for next-generation biosensors, enabling on-demand and low-cost fabrication of functional devices on flexible, stretchable, and unconventional substrates. One major challenge in this field lies in the sintering of printed features, as conventional high-temperature processing is incompatible with polymeric substrates and thermally sensitive biological components. Low-temperature sintering inks, typically processed below 200 °C or even at room temperature, have become a critical enabling technology for bio-integrated electronics. This review provides an overview of the current state-of-the-art and key challenges associated with low-temperature sintering inks for printed bioelectronics. We discuss inks based on metal nanoparticles, metal-organic decomposition precursors, metal oxides, chalcogenides, and hybrid material systems. The emphasis is on how ink chemistry, ligand selection, and precursor structure govern rheology, stability, and sintering behavior. In addition, key low-temperature sintering and curing strategies, including thermal, photonic, laser, plasma, microwave, and chemical sintering, are compared in terms of energy delivery, densification mechanisms, and substrate compatibility. Finally, we outline emerging directions towards low temperature and room-temperature sintering inks, and sustainable biobased ink formulations, and discuss their applications for wearable, implantable, and soft biosensing platforms.
Bacterial biosensors have emerged as versatile platforms for biomedical and environmental applications, yet their real-world deployment is constrained by limited signal readouts and weak integration with external devices. Two complementary research directions are now converging to address these gaps. First, emerging reporter systems expand the range of outputs beyond fluorescence and luminescence to include bioelectronic signals via extracellular electron transfer, acoustic reporter genes for deep-tissue ultrasound imaging, and hyperspectral reporters for large-scale remote sensing. Second, engineered interface layers, such as polymer and lipid coatings, DNA scaffolds, and inorganic or metal-organic composites, provide robust coupling between cells and their environments or external hardware. Together, these advances broaden the design space for bacterial biosensors and should accelerate their transition from proof-of-concept systems to practical tools for diagnostics, environmental monitoring, and living therapeutics.
Reliable single-walled carbon nanotubes (SWCNTs)-based bioelectronics have been hindered by the inability to form SWCNT films that simultaneously provide strong substrate adhesion, high areal density, and uniform electrical characteristics. Conventional deposition or linker-mediated functionalization often results in multilayered or weakly adhered networks that suffer from device-to-device variability, hysteresis, and instability in aqueous or gas environments. Building on our previously established monolayer, high-density, and highly uniform SWCNT platform created via click-chemistry-driven covalent immobilization, this work advances the material into a fully functional bioelectronic interface through a dual-click chemistry strategy. The approach integrates CuAAC-mediated covalent anchoring of polymer-wrapped SWCNTs with a subsequent copper-free click reaction for biomolecular conjugation, enabling a chemically robust monolayer that maintains structural integrity under harsh solvent sonication, repeated gate-voltage cycling, and long-term sensing operation. Devices fabricated on this dual-click SWCNT monolayer exhibit hysteresis-free electrical characteristics, excellent reproducibility across substrates, and ultrasensitive detection of both gas-phase cadaverine (LOD: 27.02 ppb) and liquid-phase cortisol (LOD: 5 pM). This study demonstrates, for the first time, that a covalently immobilized, monolayer, and high-density SWCNT network can serve as a scalable, stable, and versatile platform for molecular sensing in diverse chemical environments, establishing a unified materials-to-device framework for next-generation SWCNT bioelectronics.
Hydrogel-based wearable and implantable biosensors have quickly established themselves as a paradigm-shifting platform for continuous health monitoring. They effectively reconcile the mechanical and chemical discrepancies between conventional rigid electronics and delicate biological tissues. This success is largely attributed to the hydrogel material's inherent advantages: high water content, a precisely tunable elastic modulus, and versatile functional chemistry. Collectively, these features provide structural, biological, and processing benefits that facilitate truly seamless bioelectronic integration. This Review systematically summarizes the latest advancements in hydrogel biosensors, placing emphasis on their distinctive material attributes. These include the synergistic ionic-electronic conduction, sensitive stimuli responsiveness, advanced antifouling surface chemistry, and exceptional tissue-mimicking compliance. We further delve into the fundamental physical and chemical sensing mechanisms, supported by representative applications spanning from the non-invasive, real-time analysis of sweat, tears, saliva, and interstitial fluids to the more complex domains of subcutaneous, cardiac, and neural implants. Finally, we candidly address the crucial hurdles that remain, such as long-term hydration stability, signal fidelity drift, and adverse immune responses. Concurrently, we highlight pioneering strategies to overcome these issues, including the adoption of zwitterionic designs for enhanced biocompatibility, nanocomposite reinforcement for mechanical robustness, and the utilization of transient biodegradability. By critically elucidating the intricate relationships governing hydrogel structure, chemistry, and bioelectronic function, this Review aims to chart the research trajectory toward the next generation of durable, self-healing, and fully biointegrated sensing systems.
Chronic kidney disease (CKD) is a progressive and irreversible disorder affecting over 850 million individuals globally and is associated with significant morbidity, mortality, and healthcare burden. Conventional diagnostic approaches rely on intermittent laboratory measurements, including serum creatinine, estimated glomerular filtration rate (eGFR), and urinary albumin, which provide limited temporal resolution and fail to capture dynamic physiological changes. Recent advances in wearable biosensing technologies offer new opportunities for continuous, non-invasive monitoring of biochemical and physiological markers relevant to renal function. This review provides a comprehensive analysis of wearable biosensors for CKD monitoring, focusing on sensing mechanisms (electrochemical, optical, and field-effect transistor), biofluid interfaces (sweat, interstitial fluid, and saliva), and materials engineering strategies enabling flexible, high-performance devices. Emphasis is placed on biofluid transport dynamics, analytical performance across sampling matrices, and system-level integration with wireless communication and digital health platforms. Key challenges limiting clinical translation, including biofouling, enzymatic instability, and variability in biofluid composition, are examined-alongside emerging solutions such as antifouling interfaces, synthetic recognition elements, and multimodal sensing architectures. Finally, regulatory pathways and the role of artificial intelligence in digital nephrology are discussed. This review highlights the potential of wearable biosensors to transform CKD management through continuous monitoring, early detection, and personalized therapeutic intervention.
Accurate electrophysiological mapping of biological signals with high spatial and temporal resolution has always been an important requirement to elucidate physiological functions. Herein, we develop a photolithographic organic electrochemical transistor (OECT) matrix with two frequency-dependent channels, which can spatiotemporally map electroneurographic and neurotransmitter signals. The active material can be patterned photolithographically, forming a nanoscale interpenetrating network. The porous structure facilitates fast ion transport, establishing a high-frequency channel to monitor electroneurographic signals; meanwhile enzymatic reaction of glutamate on the surface creates a low-frequency channel to detect neurotransmitter signals, due to the relatively slow diffusion and doping processes. A low detection limit down to 900 zM for glutamate is achieved. During the test, the horseshoe network structure of the OECT array gives the device the ability of conformal contact on the surface of the cerebral cortex, avoiding the motion artifact noise, and the signal-to-noise ratio (SNR) can reach ∼40 dB. The dual-frequency channels efficiently decouple electroneurographic and neurotransmitter signals to avoid signal interference. Finally, the photolithographic matrix images dual-mode neurophysiological patterns in the cerebral cortex of mice, and can dynamically colocalize epileptic focus with high resolution for precise neurosurgical intervention.
Whole-cell microbial biosensors with electrogenic bacteria are emerging electrochemical devices that can perform complex functions, operate in challenging environments, and send and receive information electrochemically. Recent work has explored interfacing electrogenic bacteria with organic electrochemical transistors (OECTs) to produce compact electrochemical devices that can amplify extracellular electron transfer and respond more quickly than conventional devices. However, this work has focused primarily on the steady-state current produced. Understanding the dynamic sensor response to changing environmental conditions is important for utilizing microbial OECTs as real-time biosensors. Here, we study the dynamic response of OECTs interfaced with the electrogenic bacterium Shewanella oneidensis MR-1 and find that the source-drain current exhibits a first-order dynamic response to a step change in lactate concentration. By calibrating the living bioelectronic devices over a wide range of concentrations, the devices can be used as biosensors to monitor changes in lactate concentration in the solution based on the rate of change in current. We also show that the sensitivity and range of the device can be tuned through variations of the source-drain voltage, and by increasing the source-drain voltage, we demonstrate microbial devices that can detect lactate concentrations as low as 10-9 M. Finally, we implement microbial OECTs as compact, portable devices capable of quickly estimating chemical oxygen demand (COD) in wastewater and demonstrate a bacterial encapsulation strategy that enables reusable devices that operate in ambient conditions. This work advances the development of microbial sensors and provides a straightforward and easily implemented model for understanding the dynamic response of microbial bioelectronic sensors.
Wearable microneedle biosensors promise real-time molecular monitoring for precision medicine but are limited by low sensitivity and tissue abrasion. Overcoming these challenges, we recast electrode functionality not merely as a sensing substrate but as a mechanism for resilient, high signal-to-noise ratio (SNR) measurements in tissue. Our microneedle-based resilient nanostructured bioelectrode (RNB) is fabricated using a bilayer process that strengthens the electrode with a micrometer-thick gold adhesion layer and reduces fabrication-induced stress through controlled dealloying. The resulting RNBs are corrosion resistant, stable over a wide potential window, and have an artifact-free, nanocavity-textured interface. They integrate receptor-based electrochemical biosensors with enhanced SNR through increased active area, diffusion, and antifouling while remaining abrasion immune in megapascal-stiff tissues. The RNB extended in vivo biosensor lifetime for pharmacokinetics monitoring to 6 days in a freely moving rat. Paired with a blood-interstitial fluid equilibrium-based bioanalytical framework, the RNB accurately derived blood-equivalent pharmacokinetic parameters, enabling not only precision dosing of narrow therapeutic index drugs but also the direct assessment of hepatic and renal clearance. In hepatic studies, the RNB revealed delayed clearance of a chemotherapeutic (irinotecan) in liver-damaged models. In renal studies, RNB recordings correlated with blood antibiotic pharmacokinetics across chronic kidney disease severities. The RNB detected renal impairment earlier than conventional biomarker thresholds through drug clearance quantification and captured recovery under therapeutic intervention. These results establish the RNB as a viable microneedle platform for high-fidelity in vivo deployment of electrochemical biosensors, enabling minimally invasive, longitudinal monitoring of low-concentration analytes and real-time assessment of organ function.
Over the past two decades, the discovery of graphene has sparked a significant increase in research on two-dimensional (2D) materials These materials exhibit exceptional properties, including a large surface area, flexibility, and tunable electrical conductivity, making them ideal for building up wearable biosensors. Such biosensors offer rapid response times, high sensitivity, biocompatibility, and outstanding mechanical strength. This review provides a comprehensive overview of wearable biosensors based on 2D materials, highlighting their unique properties, synthesis methods, and integration into flexible electronic systems. Significant advancements, existing challenges, and commercialization prospects are explored. The development of these biosensors promises to revolutionize health monitoring and advance personalized medicine by enabling continuous, real-time monitoring of physiological parameters.
This article provides comprehensive methodological guidance for implementing rotating magnetic nanochain-enhanced lateral flow immunoassays with volumetric magnetic detection. Rotating magnetic nanochains act as microscale stirrers that substantially enhance antibody-antigen binding kinetics through convective mixing, yet their integration into lateral flow platforms presents unique technical challenges requiring both computational optimization and specialized characterization. We describe complete workflows for: (i) computational fluid dynamics modeling using COMSOL Multiphysics to simulate nanochain rotation, fluid flow, and mass transport enhancement; (ii) electron microscopy characterization of magnetic nanochain morphology and size distributions; (iii) rotating magnetic field generator design and operation; and (iv) magnetic particle quantification measurement procedures for volumetric signal readout. Each section provides step-by-step instructions with sufficient detail to enable independent replication. The described methods enable development of lateral flow assays achieving sub-nanogram detection limits with rapid (6-minute) analysis times, addressing critical needs in point-of-care diagnostics. These methods complement our related research article in Biosensors and Bioelectronics by providing the technical foundation necessary for adoption and adaptation of this technology by other laboratories.•COMSOL Multiphysics workflow for modeling convective enhancement by rotating magnetic nanochains•Electron microscopy procedures for comprehensive nanochain characterization•Instrumentation methods for rotating field generation and volumetric magnetic particle quantification.
Additive Manufacturing (AM) and Wearable Technologies (WT) have rapidly evolved over the past decade. AM offers highly customisable fabrication, while WT enables minimally invasive health monitoring. The intersection of these fields presents emerging opportunities in biomedical and engineering domains. This study aims to map the scientific landscape of AM-WT research between 2015 and 2025 through a comprehensive bibliometric analysis. A total of 718 peer-reviewed publications were extracted from Web of Science (WoS), Scopus, and PubMed, following PRISMA-ScR guidelines. Using RStudio and the Bibliometrix package, analyses included co-authorship, citation trends, keyword co-occurrence, and thematic mapping. Custom author disambiguation scripts enhanced data quality and reliability. An annual publication growth of 24.89% was observed, with notable increases after 2020. Core themes included 3D printing, biosensors, microfluidics, and organ-on-a-chip devices. A shift from manufacturing-oriented research to biomedical integration is evident. Research output is dominated by the US, China, and South Korea, with moderate but not yet highly internationalised collaboration. The field of AM-WT research is undergoing a decisive transition from fabrication-focused studies to interdisciplinary, application-driven innovations. This shift is marked by increasing integration in healthcare and bioelectronics, yet hindered by regional imbalances and thematic gaps. Addressing these will be critical to advancing global impact. This study offers a cross-database bibliometric overview of AM-WT research. By combining three major data sources, it provides enhanced coverage and introduces novel analytical dimensions to guide future interdisciplinary efforts in personalised healthcare and wearable device innovation.
One-dimensional (1D) multifunctional fibers have garnered significant attention due to their advantageous geometry properties, which allows conformal interfacing with soft biological tissues and efficient charge transport. Here, we developed a solution-deposition strategy for the scalable and cost-effective fabrication of stretchable liquid metal fibers integrated with electrochemically stable, tissue-interfacing electrodes, thereby enabling the realization of stretchable multifunctional fibers. This fiber seamlessly combines electrodes and conductive pathways into a single structure, enabling versatile applications such as electrophysiological signal sensing, in vivo nerve stimulation, and wireless energy transmission. The multifunctional fiber demonstrates significantly improved electrical performance under strain, maintaining conductivity during stretching and bending, and exhibits lower impedance and higher signal stability, particularly during physiological monitoring and electrical stimulation. The fiber's excellent biocompatibility and mechanical compliance makes it well suited for wearable systems and long-term biomedical applications, offering a robust platform for next generation 1D bioelectronics.
Underwater adhesion of polymeric adhesives is highly desirable in specific applications such as wound dressings, wearable devices, bioelectronic devices, biosensors, and water pipeline leakage repairing. However, underwater bonding is considerably different from bonding in air because interfacial water molecules substantially weaken the intimate contact adhesion between the adhesive and submerged surfaces, thus significantly limiting the application of adhesives in various fields. This review was compiled by searching relevant references on PubMed database (before April 2025) based on selected keywords. Recently, many wet adhesion technologies and diverse and flexible adhesive materials have been employed to address the weak adhesion strengths and inferior mechanical properties in underwater environments. Among several strategies, mussel-inspired catechol-based underwater adhesion has gained the attention of scientists because mussel-inspired tissue adhesives (TAs) demonstrate numerous advantages including many interactions with substrates, various designs of some interesting smart TAs, and excellent adhesion based on several interfacial interactions dominated by 3,4-dihydroxyphenylalanine, a catecholic amino acid in mussel adhesive proteins. We discuss the mechanism of catechol-based underwater adhesion, classification of underwater adhesives, and characteristics, applications, advantages, and disadvantages of dopamine (DA)-modified polymeric TAs. Furthermore, we review stimuli-responsive TAs and the essential factors affecting the adhesions of DA-modified TAs in underwater environments. Finally, we discuss some current technical challenges and future perspectives for underwater adhesion.
This work set out to establish an easily applicable system to improve a broad range of bioelectronic devices using the SpyTag-SpyCatcher crosslinking system together with one of the model organisms for extracellular electron transport, Shewanella oneidensis. Therefore, the surface-displayed c-type cytochrome MtrC was equipped with an accessible SpyTag and coupled to SpyCatcher-functionalized surfaces. A transposon screen followed by nanopore sequencing was conducted in order to identify integration positions which facilitate MtrC functionality while the SpyTag is surface accessible. Three integration positions (W314, Y417, T603) were chosen for further characterization. Expression of the MtrC-SpyTag constructs in a S. oneidensis strain lacking all outer membrane cytochromes restored the ability to reduce an extracellular electron acceptor. Two of the three strains reached reduction rates at the wildtype MtrC level proving that the integrated SpyTag does not hamper extracellular electron transfer. In vivo, all three constructs showed significantly better binding properties to SpyCatcher functionalized magnetic beads than the wildtype MtrC control. The two most promising candidates were coupled to conductive, magnetic gold nanoparticles and directed towards a screen-printed electrode showcasing how MtrC-SpyTag expression can improve bioelectronic devices. A significantly higher charge transfer compared to the wildtype control was reached in linear sweep voltammetry and chronoamperometry experiments. Moreover, a shift towards direct electron transfer was observed which reduces the problem of redox shuttle washout in flowthrough systems. Direct binding of the cells to SpyCatcher functionalized electrodes enabled robust current production even after thorough washing of the electrodes while control cells failed to produce current under these conditions. The versatile SpyCatcher toolbox can be used together with the here reported strains to eliminate bottlenecks in bioelectronics like poor biofilm formation or the production of an insulating extracellular polymer matrix.
As one of the most classical and well-characterized enzymes in modern biochemistry, lactate dehydrogenases (LDHs) are versatile oxidoreductases with broad functional and technological relevance. They serve as central components in diagnostic kits, biosensors, bioelectronics, and biocatalytic systems. Bacterial LDHs, in particular, stand out for their intricate regulatory features and remarkable robustness, making them suitable for industrial applications and necessitating a rational framework for their redesign. This paper reviews the structural attributes and catalytic mechanisms of both D-LDHs and L-LDHs from diverse bacterial species, highlighting the molecular determinants that govern their distinct enzymatic behaviors. The functions of key amino acid residues involved in catalysis, allosteric regulation, and cofactor binding are discussed, together with recent advances in genetic engineering and immobilization strategies that enhance enzyme yield and stability. Collectively, these insights provide a conceptual framework for the rational design of LDH variants with properties tailored to specific applications. Finally, unresolved literature gaps, emerging opportunities, and prospective directions for bacterial LDHs are explored in relation to their expanding roles in biotechnology across the environmental, medical, and materials sciences.
Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) are attractive building blocks for bioelectronics owing to their programmable porous structures, rich host-guest chemistry, and tailorable functionalities. Organic photoelectrochemical transistors (OPECTs), which couple light-addressable redox transduction of photoelectrochemical sensing with the intrinsic signal amplification of organic transistors, have recently emerged as promising bioanalysis platforms. By synergizing the functionalities of MOFs and COFs, here we present a cathodic OPECT bioanalysis by using a hemin-incorporated ZIF-8 (Hemin@ZIF-8) biological MOF (bioMOF) to augment the performance of a photocathodic TpPa-Cl COF. The platform operates via a split-type cortisol-targeted sandwich immunorecognition using glucose oxidase (GOx)-labeled detection antibodies, where the immunocaptured GOx catalyzes the oxidation of glucose to gluconic acid, leading to the disintegration of the pH-responsive bioMOF on the gate and thus the release of encapsulated hemin. The released hemin serves as an efficient electron acceptor for photoexcited electrons in the photocathodic COF, suppressing carrier recombination and enhancing the photoelectric response of the device. The as-developed cathodic OPECT delivers sensitive cortisol detection with an ultralow detection limit of 1.0 fg mL-1. By harnessing the synergy between bioMOFs and COFs, this work introduces a novel approach to gate OPECTs, revealing their potential for high-performance optoelectronic bioanalysis.