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.
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.
Biosensors and bioelectronics (B&B) are typical devices working at the interfaces of biology and electronics [...].
Hydrogels are promising materials for constructing next-generation bioelectronics because of their excellent biocompatibility and mechanical compliance. Yet, creating robust and multifunctional hydrogel devices that conform to the surface of 3D organs remains challenging. Here, we report a biomimetic strategy for engineering ultrathin and ultrastrong hydrogel membranes as an advanced platform for organ-conformal bioelectronics. In these hydrogels, self-organized nanofiber networks confer strain-stiffening characteristics with a phenomenal combination of high mechanical strength (∼13.65 MPa), fracture toughness (∼21 573 J/m2), and low initial stiffness (∼600 kPa), which accommodates the construction of ultrathin membranes (∼10 μm thickness) reconciling mechanical robustness and 3D conformability. Theoretical simulations reveal unique strengthening mechanisms originating from the topological reconfiguration of fibrillar joints, indicating a widely applicable principle for designing soft composites involving 3D fibrillar networks. We show that various electronic components, including conducting polymers and wafer-fabricated microelectronic sensors, can be integrated on the ultrathin hydrogel membranes, providing means for multimodal physiological sensing and stimulation. These hydrogel membranes open paths to robust, functional and biocompatible interfaces with 3D soft organs and tissues, which are useful for epidermal electronics, implantable brain-machine interfaces, peripheral nerve stimulation, and many other bioelectronic applications.
Epidermal patches are multifunctional skin-interfacing platforms with applications spanning wound management, real-time biosensing, drug delivery, and tissue regeneration. Hydrogels play a central role due to their mechanical compliance, water-rich composition, and tunable physicochemical properties. Key design features flexibility, stretchability, self-healing, and self-adhesion, which ensure stable skin contact and device stability. Tailored electrical conductivity, enabled by conductive polymers, fillers, and novel fabrication strategies, allows seamless integration with bioelectronics for intelligent health monitoring. Fabrication innovations, such as 3D/4D printing, stereolithography, digital light processing, extrusion-based writing, inkjet printing, electrospinning, and microneedle-based platforms, allow precise spatial control and multifunctional integration. Emerging approaches, including AI-assisted biosensing, stimuli-responsive drug release, noninvasive skin metabolite monitoring, and biodegradable systems, further expand their potential. Applications range from infection-resistant wound dressings and minimally invasive drug delivery to acne therapy, cardiac patches, and hydrogel micropatch probes for skin metabolomics. Challenges remain in achieving scalable manufacturing, long-term durability, and material sustainability. Future development will converge intelligent hydrogel design, integrated biosensing, data-driven analytics, advanced metabolomics, and personalized transdermal therapeutic, transforming epidermal patches from passive materials into adaptive, closed-loop biointerfaces capable of sensing, decision-making, and on-demand intervention. By uniting therapeutic, diagnostic, and protective functions, hydrogel-based epidermal patches are set to revolutionize personalized healthcare.
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.
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.
Organic electrochemical transistors (OECTs) are promising for bioelectronics and low-power logic owing to their mixed ionic-electronic conduction and mechanical softness. However, thermoelectric gating of OECTs remains unexplored due to the incompatibility of rigid, electronically dominated thermoelectric modules with hydrated soft systems. Here, we introduce printable thermoelectric ionogels with n-p convertible thermopower, where the Seebeck coefficient is tunable from -3.61 to +9.74 mV K- 1 through facile [EMIm][Cl] doping. These ionogels act simultaneously as thermoelectric legs and ionic dielectrics, enabling direct integration with OECTs to realize soft, complementary p-n thermoelectric modules. We demonstrate thermoelectric gating of both BBL- and p(g2T-T)-based OECTs, achieving high on/off ratios (>103) and robust transconductance under low temperature gradients (<30 K), while retaining mechanical stretchability. This strategy provides a general framework for coupling thermoelectric functionality with OECTs, opening new avenues for energy-autonomous, flexible electronics with built-in thermal sensing and adaptive control.
Simultaneous interrogation of cardiac electrophysiological and metabolic processes is essential for investigating and treating heart disease. Key challenges remain in creating stretchable multimodal bioelectronic devices capable of organ-scale, label-free probing of electrophysiology and metabolism in vivo. Here, we present stretchable, scalable, large-area transparent microelectrode arrays (MEAs) that integrate up to 144 microelectrodes and interconnects, enabling a centimeter-scale field of view to tackle these challenges. The microelectrodes consist of conductive polymer-coated metal nanowire composites with outstanding optical transparency and electrochemical performance for both electrophysiological sensing and electrical pacing. These large-area arrays exhibit excellent yield, uniformity, biocompatibility, and mechanical deformability like native cardiac tissue. They successfully achieve in vivo spatiotemporal mapping of electrophysiological activity together with colocalized label-free autofluorescence imaging of metabolism across all four beating heart chambers under clinically relevant conditions in small animals, including ischemia, arrhythmia, and device-delivered electrotherapy. The platform offers methodological opportunities to advance basic and clinical cardiology.
Flexible piezoelectric materials demonstrate broad application potential in wearable health monitoring, human-machine interaction, and biosensing. However, the piezoelectric response of pure PVDF-TrFE is limited and insufficient to meet the requirements for highly sensitive sensing. In this study, ZnO/PVDF-TrFE composite films with varying ZnO doping contents (3-11 wt%) were fabricated and systematically characterized in terms of their structural, thermal, and electrical properties. The results indicate that ZnO significantly promotes the formation of the polar β-phase in PVDF-TrFE, with the maximum β-phase content (Fβ = 24.76%) and optimal piezoelectric performance achieved at 9 wt% ZnO doping. Devices based on this optimal composition exhibited stable ultrasonic transmission and reception capabilities under high-frequency pulse excitation, enabling sensitive detection of minor static pressure variations (e.g., contact pressure) through changes in ultrasonic echo signals, thereby realizing wearable conformity monitoring. Moreover, a sensor designed with a three-channel flexible substrate successfully captured human wrist pulse signals with high accuracy, demonstrating the practical utility and reliability of the device in flexible bio-electronic sensing applications.
The past decade has witnessed a fundamental shift in 2D nanomaterials, from isolated single-component sheets to vdW nanohybrids, architected as stacked, stitched, or surface-engineered assemblies of chemically distinct layers. Enabled by weak interlayer forces, these hybrids permit modular integration of photonic, catalytic, electronic, and bioactive functions without lattice matching or harsh chemistries. In biomedicine, this modularity is transformative: one layer can absorb Near Infrared, NIR light for photothermal or photodynamic therapy, another can intercalate and release drugs or nucleic acids, a third can modulate redox biology through ROS scavenging or nanozyme activity, while polymeric or biomimetic coatings provide immune evasion, targeting, or biodegradability. Compared with isotropic nanoparticles, 2D vdW interfaces offer maximal surface area, multivalent binding, anisotropic ion/electron transport, tissue-compliant mechanics, and engineerable interlayer galleries for controlled, stimulus-responsive release. Crucially, vdW stacking preserves the intrinsic properties of each layer while enabling emergent synergistic behaviors including photothermal-photodynamic coupling, catalytic-photonic amplification, mechanobiology-driven responsiveness, and staged therapeutic logic. Together, these attributes position vdW nanohybrids as a powerful and versatile class of materials poised to redefine therapeutic, diagnostic, regenerative, and bioelectronic frontiers in next-generation nanomedicine.
Spinal cord stimulation (SCS) is a surgical therapy for chronic neuropathic and mixed-origin pain refractory to conventional treatments. Patient selection considering both clinical and psycho-social factors is essential. This study prospectively validated an online e-health tool for SCS candidate selection and compared its recommendations with expert physician judgment. A total of 80 patients (aged 18-85 years) with persistent spinal pain syndrome, complex regional pain syndrome, neuropathic pain syndromes, or ischemic pain syndromes were enrolled at a single pain unit (December 2020-May 2024). Clinical, demographic, and psycho-social variables were collected and entered into the SCS e-health tool, which provided implantation recommendations. Physicians blinded to the tool output rated the probability of trial success. The patients underwent a 45-day SCS trial, followed by implantation in responders. Agreement between tool recommendations and expert judgment was assessed using Fisher exact test and Cohen's κ. Overall, 69 patients (86.3%) showed positive trial results and were implanted. Success rates corresponded to tool recommendations: 100% for "strongly recommended," 86.2% for "recommended," and 57.1% for "rarely recommended" (p = 0.0214). One-year follow-up confirmed sustained benefits in the strongly recommended group. Agreement between the tool and physician judgment was moderate for clinical variables (unweighted κ = 0.51, weighted κ = 0.54) and fair/moderate when including psycho-social variables (unweighted κ = 0.38, weighted κ = 0.44). Pain intensity and disability were relieved over time. The SCS e-health tool is a reliable aid for selecting candidates, integrating clinical and psycho-social factors reflecting trial and long-term outcomes. It can guide clinicians in identifying patients most likely to benefit from SCS and support preimplant decision-making.
Two-dimensional (2D) sliding ferroelectrics promise an ultrathin, fatigue-free platform for reconfigurable electronics, but their development has been hindered by a strict requirement for lattice matching, which limits the material choice and functionality. Here, we overcome this limitation by demonstrating room-temperature sliding ferroelectricity in a lattice-mismatched semiconducting MoS2/ReS2 heterobilayer. This van der Waals semiconductor displays robust switchable resistive states with submicrosecond dynamics and an endurance exceeding 105 cycles. Building on these properties, we developed a ferroelectric field-effect transistor-based biosensor (bio-FeFET) for label-free detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a key biomarker for oxidative DNA damage. The polarization-induced field enhances electrostatic enrichment of negatively charged aptamers, achieving high sensitivity and an ultralow limit of detection (LoD). Importantly, polarization reversal enables a reconfigurable "write-read-erase" operation, thereby allowing the electrical regeneration of the sensing interface without chemical treatment. These findings not only broaden the material horizon for sliding ferroelectrics but also support the development of high-sensitivity, reconfigurable bioelectronic interfaces for logic-integrated sensing.
Nanobody-based biosensors promise exceptional molecular recognition and robustness, but their implementation has been limited by unstable and non-scalable surface chemistries. Here we introduce a materials platform that integrates stable electropolymerized tyramine nanofilms with label-free, non-faradaic electrochemical impedance spectroscopy for direct molecular detection. The electropolymerized nanofilms form amine-functionalized coatings that are electrically insulating yet chemically active, supporting site-specific covalent immobilization of nanobodies in controlled orientations. Target binding induces more than a 50% increase in the capacitance signal response, providing a distinct label-free signature of molecular recognition. The platform can be adapted to diverse bioreceptors and antifouling layers, offering a general route to chemically robust and scalable bioelectronic interfaces. By decoupling film conductivity from functional stability, this work establishes a new class of interfaces that bridge molecular design with label-free signal transduction for next-generation biosensing technologies.
Previous optogenetic bioelectronic systems have enabled a highly selective way of modulating neural populations by delivering a certain wavelength of light to engage with exogenously expressed light-sensitive proteins, which lay the foundation of therapeutic interventions of neural circuits. However, real-time biofeedback and strategic modulation are crucial for adjusting customized clinical treatment adjustment. To achieve this purpose, we integrated illumination, temperature, and electromyographic (EMG) sensing elements into the optogenetic bioelectronic system to avoid overexposure caused by localized overheating and to provide functional recovery evaluation during neural regeneration, which guides the in situ adjustment of the intensity, frequency, and duration of illumination parameters controlled by a wireless connected programmable external control board. In this study, both in vitro and in vivo experiments were performed to examine the optical, thermal, and electrical characteristics of our bioelectronic system. On this basis, we demonstrated a series of standardized EMG results to evaluate the recovery condition and modify the illumination parameters of each test rat. Combining temperature monitoring feedback and EMG signaling feedback, our optogenetic bioelectronic system enables strategic optogenetic spinal cord injury (SCI) treatment through real-time illumination modulation to achieve customized spinal cord injury treatment.
Liquid crystal polymer (LCP) is increasingly used in flexible implantable bioelectronic devices due to its low moisture uptake, chemical stability, and ability to form robust thermoplastic bonds. However, integrating fine-pitch thin-film metallization into bonded embossed LCP structures presents challenges related to pattern fidelity, bond integrity, alignment accuracy, and long-term electrical reliability, particularly when the metal thickness is small relative to the surface roughness. In this work, we present and characterize a fabrication process for integrating a 500-nm-thick sputtered Cr/Au thin-film metallization onto a 25-μm-thick embossed high-temperature LCP (HT-LCP) substrate, patterned into long (20 cm) and narrow (8 μm) traces using lift-off. Bond integrity between the metallized HT-LCP and a low-temperature LCP (LT-LCP) layer was evaluated using peel testing, while structural and electrical integrity were assessed using NanoCT imaging and resistance measurements. Long-term reliability was evaluated using reactive accelerated aging (RAA) at 87 °C in physiological saline with 10 mM hydrogen peroxide. The results show that the thin metal layer does not degrade bond strength and that embedded traces maintain structural and electrical integrity through bonding and aging. After 12 days of RAA testing, no measurable changes in electrical performance were observed. Electrochemical impedance spectroscopy demonstrated that electrodes coated with a 100-nm sputtered Pt layer exhibited approximately 2 × lower impedance than flat Pt electrodes, attributed to increased surface roughness. Additionally, the bonded LCP structure was thinned from 50 μm to 10 μm using CF4/O2 reactive ion etching with >90% uniformity. These results demonstrate that thin-film metallization integrated into bonded embossed LCP systems can achieve high interconnect density without compromising mechanical or electrical reliability. This work provides practical guidelines for the design of thin, flexible, and durable LCP-based implantable bioelectronic devices.
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Wearable bioelectronic systems require soft, deformable materials that maintain high electrical conductivity and reliable interfacial charge transport under large mechanical strains. However, most existing hydrogel- or elastomer-based conductors involve trade-offs among mechanical compliance, electrical performance, and long-term biocompatibility, making it challenging to integrate all three properties within a single material platform. Here, we introduce a plasmonic hot-electron-assisted conductive PAM-PEDOT:PSS-Ag hydrogel, engineered to address these multifunctional requirements for continuous cardiovascular monitoring. Silver nanoparticles (Ag NPs) dispersed within the hydrogel matrix generate localised surface plasmon resonance (LSPR) under UV irradiation, producing smooth, spatially uniform heating and hot-electron injection throughout the precursor solution. This synergistic plasmonic heating effect accelerates polymerisation (∼420 s; 0.1167 h), enhances network homogeneity, and lowers interfacial charge-transfer resistance by promoting more ordered PEDOT:PSS chain assembly and improved crosslinking dynamics. As a result, the hydrogel exhibits ultrahigh stretchability (>2000%), stable conductivity (∼328.82 ± 1.78 mS m-1), and intrinsic antibacterial activity (≥99.7%). The material exhibits consistent electromechanical performance from -20 °C to 40 °C, showing tunable strain sensitivity governed by temperature-dependent network mechanics and ionic mobility. When used as epidermal electrodes, the hydrogel enables high-fidelity electrocardiogram (ECG) acquisition (SNR ≈ 25 dB) in human and rodent models. Integrated with machine-learning analytics, the platform supports accurate demographic prediction (96.2%), demonstrating a scalable material-device-data framework for next-generation personalised cardiovascular monitoring.
Cardiorespiratory coupling (CRC) reflects coordination between heart and lung function, but how it changes with increasing intensity during graded exercise remains unclear. We investigated CRC as real-time covariation between cardiac timing and breath-by-breath pulmonary oxygen uptake (VO2) to test whether coupling strengthens with workload in adolescent athletes. We conducted an observational, within-subject analysis of the ACTES cycling dataset. Eighteen adolescents cycled at 50, 110, and 140 W. Beat-to-beat RR intervals and pulmonary VO2 time series were examined in ultra-short 60 s segments. Fluctuations were summarized using SDRR/RMSSD and SDVO2/RMSSDVO2. CRC was measured using joint symbolic dynamics (JSD; Shannon entropy, SE, and Miller-Madow-corrected entropy, CSE) and the highest normalized cross-correlation (X-Corr). Mean RR decreased and mean pulmonary VO2 increased with workload (both p < 0.0001). SDRR and RMSSD were lower at 110 and 140 W versus 50 W; SDVO2 declined from 50 to 110/140 W, whereas RMSSDVO2 was unchanged. X-Corr increased from 50 to 110/140 W (p ≤ 0.0014). JSD indices decreased as workload increased (SE: global p = 0.139; CSE: global p = 0.029), suggesting tighter CRC. CRC becomes more pronounced with increased workload, aligning with reduced heart rate variability and reflecting vagal withdrawal and reflex responses that improve heart-lung integration in adolescent athletes.