Long-term stability of neural interfaces is frequently compromised by mechanical mismatch and chronic neuroinflammation, often leading to electrode detachment and signal failure. While hydrogel coatings offer a solution, conventional designs typically rely on exogenous conductive fillers that can sacrifice mechanical flexibility or induce toxicity. Here, we report on a soft neural interface based on the supramolecular co-assembly of a renewable natural polysaccharide, okra mucilage polysaccharide (OMP), and an α-helical peptide amphiphiles (APA). The resulting OMP-APA hydrogel (OP gel) exhibits environment-responsive enhancements in bioadhesion and charge-transport capability triggered by physiological pH and electrical stimulation. These properties arise from intrinsic, stimulus-responsive alterations in fibre architecture and orientation, eliminating the need for conductive fillers. Leveraging interfacial liquid-liquid phase separation, we demonstrate the in situ coating of ultra-thin OP-gel coating onto carbon fibre electrodes (CFE). The OP-gel-coated electrodes (OP-CFE) significantly mitigate foreign body responses and glial scarring, enabling stable, high-quality neural recordings in a mouse cortical in vivo model. Our findings provide a versatile strategy for constructing seamless, multifunctional bio-interfaces through supramolecular co-assembly, with broad implications for advancing neural prosthetics and neuroscience research.
G-triplexes are noncanonical DNA structures formed by three guanine tracts, but their sequence design rules for small-molecule binding remain unclear. In this work, we carried out a systematic sequence screening to optimize G-triplex sequences for improved interaction with methylene blue (MB), and applied the best sequence in an electrochemical biosensor for melamine detection. Over 80 candidate sequences were designed by varying loop nucleotides, 5'-flanking bases, and strand length, and were evaluated by square wave voltammetry. The optimal sequence F9 (5'-ATGGGAGGGTGGG-3') achieved the highest current suppression (ΔI/I0 ≈ 0.81), outperforming all tested G-triplex and several well-known G-quadruplex sequences. Circular dichroism confirmed that F9 folds into a parallel G-triplex with a melting temperature of 65.1 °C, which increased to 70.0 °C upon MB binding. Electrochemical titration gave a 1:1 binding ratio with an association constant of 9.37 × 105 M-1. Molecular dynamics simulations showed that MB binds to the 5'-face of the G-triplex by π-π stacking, with a computed binding free energy of -151.9 kJ/mol. A hairpin probe (MelaPin) combining the F9 sequence with a poly-T melamine recognition region was then constructed. The resulting biosensor showed a linear response over 1-100 μM melamine with a detection limit of 0.74 μM, and a recovery of 96.0 ± 0.8% in spiked infant formula. This work provides a practical framework for G-triplex sequence design and shows that the G-triplex/MB system can serve as a simple, label-free signal module for electrochemical sensing.
The light-addressable electrochemical sensor (LAES) enables spatially resolved electrochemical measurements without the need for physical interconnects and fixed electrode geometries. However, current LAES constructions predominantly rely on rigid inorganic semiconductors, limiting their compatibility with flexible electronics. Herein, we present a novel LAES platform based on the organic semiconductor poly(1,3,5-triethynylbenzene) (PTEB), synthesized via a mild copper-catalyzed Glaser coupling reaction. The resulting PTEB film exhibits an interconnected porous network morphology and a direct bandgap of 2.15 eV, along with strong photoelectrochemical responsiveness, high pH sensitivity, and microscale imaging resolution. Particularly, PTEB films deposited on conductive polyester substrates retained 95 % of their photocurrent response under mechanical bending, underscoring excellent mechanical stability. This work addresses key limitations of conventional inorganic semiconductor-based LAES and provides a promising material platform for the development of next-generation flexible and wearable LAES devices.
Light-addressable electrochemistry (LAE) enables the activation and detection of localized faradaic electrochemical processes on a flat, unconstructed semiconductor electrode through targeted light illumination, making it a promising approach for single-cell electrochemistry. Herein, we report a direct current (DC) redox imaging technique for single retinal pigment epithelial cells utilizing LAE with an α-Fe2O3 electrode activated by a constant, focused laser beam. The proposed DC-LAE method showed micron-scale resolution and was successfully used to image single cells under physiological conditions. We demonstrated that the visualization was primarily due to the hindrance of photoinduced OH- oxidation by adherent cells, resulting in a reduction of local photocurrents. Inspired by this funding, electroactive substances with high redox activities, such as hydroquinone (HQ), l-ascorbic acid (AA), and potassium ferricyanide (K4Fe(CN)6) were introduced into the culture medium. These substances significantly enhanced the DC redox imaging performance under low-intensity laser conditions without compromising cell viability. We believe that integrating pure DC-LAE with cell imaging advances quantitative analyses of cellular electrochemical behavior, offering valuable insights into cellular functions and processes.
Cell adhesion to the extracellular matrix (ECM) regulates essential biological processes and plays a critical role in disease progression. Current adhesion assays often rely on labeling or lack single-cell resolution. Here, we present a phase angle-responsive light-addressable electrochemical sensor (LAES) for label-free, single-cell imaging of cell-substrate adhesion. By analyzing the phase angle, which is the temporal offset between voltage and photocurrent, we achieve robust detection of interfacial dielectric changes, overcoming limitations of conventional amplitude-based LAES. This platform enables the quantitative assessment of cell adhesion across diverse cell types and semiconductor substrates. Dynamic modulation of adhesion using ECM coatings and trypsin treatment further confirms the sensitivity of phase angle imaging to adhesion strength. A point-contact electrical equivalent circuit model supports the observed correlation between phase angle shifts and cell-substrate junction resistance. This work establishes phase angle-based LAES as a powerful tool for single-cell adhesion mapping with strong potential for mechanobiology and adhesion-targeting therapeutic screening.
Accurate and reliable gesture recognition using electrical impedance tomography (EIT) holds significant potential for human-computer interaction and assistive technologies, yet ensuring consistent performance across multiple sessions remains challenging due to factors such as system noise, electrode shifts, and frequency-dependent signal variation. To address these issues, we propose an optimized EIT-based gesture recognition system featuring a dual-ring electrode configuration, an enhanced classification algorithm, and a high-frame-rate data acquisition approach. By systematically examining the similarity evaluation index (SEI) at various frequencies, we identified 10 kHz as the optimal operating frequency, achieving an SEI of 16.5%, substantially exceeding the baseline SEIL value. Our improved neural network architecture, PEU-SFU-ResNet50, further enhances feature extraction and classification robustness, attaining 88.18% accuracy in intersession tests-approximately 12% higher than the baseline model-and demonstrating 98% accuracy in single-session scenarios, outperforming standard ResNet50 and artificial neural network (ANN). Ablation experiments and cross-validation validated the efficacy and robustness of our proposed system, underscoring its potential for multisession gesture recognition applications.
The light-addressable electrochemical sensor (LAES) is a powerful tool for single-cell imaging due to its label-free and probe-free advantages. In this work, we report a photocurrent polarity-switchable LAES using a single-phase photoelectrode of a BiFeO3 thin film for living cell imaging. The proposed BiFeO3 could show both p- and n-type photocurrent behavior by simply altering the external bias voltage. LAES imaging of the same individual MCF-7 cells was performed in anodic and cathodic modes. Decreases in both photocurrents were observed due to the hindering effect of the adherent cells on local photoinduced Faraday currents. Furthermore, the dynamic photocurrent changes on cells after trypsin treatment were imaged and studied at anode and cathode polarities. Both polarities showed an increase in local photocurrents on cells as the cell-substrate junction weakened, and this change displayed heterogeneous characteristics. This is the first time that LAES cell imaging was achieved in a p-type mode. Meanwhile, our photocurrent polarity-switchable imaging approach overcomes the limitations of conventional photoelectrodes, which have been confined to single-polarity operation. We believe this work has the potential to significantly broaden the application scope of LAES in single-cell visualization and analysis, offering great insights into cellular behavior and function.
This study introduces an EIT -based gesture recognition system focusing on the entire arm, including hand movements. Utilizing a 16-electrode system and the Gauss-Newton method, we conducted experiments with six participants, testing various gestures at frequencies of 1 kHz, 10 kHz, and 100 kHz. The introduced Similarity Evaluation Index (SEI) identified 10 kHz as a potentially optimal testing frequency, exhibiting an 11 % difference in relative conductivity. Repeated measurements demonstrated system stability, while individual variations underscored the complexity influenced by behavioral habits and physiology. Future endeavors aim to refine sensitivity, expand the gesture repertoire, and explore practical applications, positioning this work at the forefront of human-technology interaction research.
The multiplexed detection of metabolites in parallel within a single biosensor plate is sufficiently valuable but also challenging. Herein, we combine the inherent light addressability of silicon with the high selectivity of enzymes, for the construction of multiplexed photoelectrochemical enzymatic biosensors. To conduct a stable electrochemistry and reagentless biosensing on silicon, a new strategy involving the immobilization of both redox mediators and enzymes using an amide bond-based hydrogel membrane was proposed. The membrane characterization results demonstrated a covalent coupling of ferrocene mediator to hydrogel, in which the mediator acted as not only a signal generator but also a renewable sacrifice agent. By adding corresponding enzymes on different spots of hydrogel membrane modified silicon and recording local photocurrents with a moveable light pointer, this biosensor setup was used successfully to detect multiple metabolites, such as lactate, glucose, and sarcosine, with good analytical performances. The limits of detection of glucose, sarcosine and lactate were found to be 179 μM, 16 μM, and 780 μM with the linear ranges of 0.5–2.5 mM, 0.3–1.5 mM, and 1.0–3.0 mM, respectively. We believe this proof-of-concept study provides a simple and rapid one-step immobilization approach for the fabrication of reagentless enzymatic assays with silicon-based light-addressable electrochemistry.
Multi-channel evaluation on a single sensor interface is highly valuable but full of challenge. Herein, a universal light-addressable electrochemical immunoassay based on silicon photoelectrodes was proposed for spatially -resolved detection of prostate-specific antigen (PSA) as a model target. To stabilize and functionalize silicon substrate, a simple and robust antifouling coating was prepared by cross-linking bovine serum albumin (BSA) matrix with glutaraldehyde (GA). For the PSA detection, an electrochemical sandwich-type immunosensor was performed on the basis of BSA@GA functionalized silicon, in which horse radish peroxidase (HRP) was used to catalyze the reaction of H2O2 and hydroquinone (HQ), resulting in in situ generation of benzoquinone (BQ). The light-induced local reduction photocurrent of BQ was then recorded as the sensor response by irradiating the target spot of photoelectrode respectively with a moveable light pointer. The results demonstrated the feasibility of localized measurements of enzymatic reactions. Coupling with light-addressable electrochemistry (LAE) and enzyme-linked immunosorbent assay (ELISA) protocol, multiplexed PSA detection could be achieved on a single sensor chip with good sensitivity and specificity. This proof-of-concept study provides a promising platform for high-throughput and accurate immunoanalysis in diagnostic or biodefense applications.
The application of silicon (Si) substrate as photoelectrode in light-addressable electrochemistry (LAE) is severely limited due to its ease of surface oxidation. The resulted silicon oxide (SiOx) layer is electronically insulating and blocks charge transfer between the electrode and electrolyte. Keeping the Si from being oxidized is a key challenge for its practical use as a semiconductor electrode. In this work, we find that by developing a thin layer of polydopamine film on the surface of Si substrate, followed by carbonization at 550 °C, the natural oxidation of Si substrate can be successfully forestalled. When applied as an electrode, it is further found that the carbonized polydopamine (cPDA) layer can also prevent anodic oxidation of Si. The cPDA layer-modified Si substrate exhibits good photoelectrochemical performance and great stability, with no obvious signal decrease under ambient environment over 32 h. Our work here provides a new modification strategy for anti-oxidation of Si substrate and it is promising in the application of light-addressable electrochemical sensing and imaging.
Label-free electrochemical visualization of cancer cell apoptosis is essential for cancer therapies. In this work, we proposed a noninvasive imaging method using a light-addressable electrochemical sensor (LAES) for label-free imaging of drug-induced tumor cell apoptosis. The dynamic AC photocurrent changes on MCF-7 human breast adenocarcinoma cells after inducing by tamoxifen were imaged. And the reasons for photocurrent changes on the cells were explored by monitoring the changes in the ζ potentials of cells and Faradic impedance. The results demonstrated that the AC photocurrent on apoptotic MCF-7 cells increased, and the apoptosis degree of each cell was heterogeneous. Moreover, the AC photocurrent increase was attributed to the increased cell membrane permeability and the increased gap between the cell basal surface and the substrate caused by cell apoptosis. This study provides a brand new approach for label-free visualizing cell apoptosis heterogeneity, which has great potential in apoptosis-associated drug screening or drug efficacy evaluation.
The light-addressable electrochemical sensor (LAES) is a recently emerged bioanalysis technique combining electrochemistry with the photoelectric effect in a semiconductor. In an LAES, a semiconductor substrate is illuminated locally to generate charge carriers in a well-defined area, thereby confining the electrochemical process to a target site. Benefiting from the unique light addressability, an LAES can not only detect multiple analytes in parallel within a single sensor plate but also act as a bio(chemical) imaging sensor to visualize the two-dimensional distribution of specific analytes. An LAES usually has three working modes: a potentiometric mode using light-addressable potentiometric sensors (LAPS) and an impedance mode using scanning photoinduced impedance microscopy (SPIM), while an amperometric mode refers to light-addressable electrochemistry (LAE) and photoelectrochemical (PEC) sensing. In this review, we describe the detection principles of each mode of LAESs and the concept of light addressability. In addition, we highlight the recent progress and advance of LAESs in spatial resolution, sensor system design, multiplexed detection, and bio(chemical) imaging applications. An outlook on current research challenges and future prospects is also presented.
A miniaturized platform combining integrated microelectrode (IME) and functional nucleic acids was developed for homogeneous label-free electrochemical biosensing. IME was constructed with a carbon fiber microelectrode and a platinum wire in a θ type glass tube as a two-electrode system for electrochemical monitoring at microliter level. A newly reported G-triplex/methylene blue (G3/MB) complex was used as the signal generator in the homogeneous label-free electrochemical biosensor. G3 has strong affinity with MB and it can cause significant decrease of the diffusion current of MB after binding. Melamine was chosen as the model target. Since melamine can interact with nucleobase thymine (T) to form T-melamine-T structure through complementary hydrogen bonds, a single-strand functional DNA hairpin structure with poly T and G3 elaborately blocked via base pairing was designed. The presence of melamine can trigger the conformation switching of the DNA hairpin to release the G3. The released G3 combined with MB could therefore change the diffusion current, leading to a simple and rapid detection of melamine. The combination of functional DNA hairpin as target recognition element, G3/MB as signal generator, and IME as transducer provided a “Mix and Measure” miniaturized platform for the construction of homogeneous label-free electrochemical biosensors.
Here, we describe a new photoelectrochemical imaging method termed light-addressable square wave voltammetry (LASWV). It measures local SWV currents at an unstructured electrolyte/insulator/semiconductor (EIS) field-effect substrate by illuminating and addressing the substrate with an intensity-constant laser. Due to the continuous generation of charge carriers in the light-irradiated semiconductor, the drift and diffusion of photoinjected carriers within the semiconductor bulk would slow down the equilibrium processes of charge and discharge in one potential pulse cycle. Therefore, even though SWV is sampled at the end of the direct and reverse pulses to reject capacitive currents, in our approach, photoinduced capacitive current can still be detected as an effective sensory signal. The obtained current-potential (I-V) curve shows a typical shape corresponding to the accumulation, depletion, and inversion regions of field-effect devices. We demonstrated that LASWV can be used as a field-effect chemical sensor to measure the solution pH and monitor enzymatic reactions. More importantly, since the charge carriers are only generated in the illuminated area, the laser spot in the device can be used as a virtual probe to record local electrochemical properties such as impedance with microresolution.
Light‐addressable potentiometric sensor (LAPS) is highly attractive in many sectors, including human disease detection, drug screening, and environmental monitoring. Currently, classical LAPS chips adopt inorganic semiconductors, such as silicon, as the photosensitive layer. Organic semiconductors can provide the next generation of the photosensitive layer because of their high absorption efficiency, large structural variability, eco‐friendliness, and bendability. However, no promising organic materials have been reported so far for the construction of LAPS chips. Here, the authors demonstrate the potential of fullerene (C 60 ), a π‐conjugated carbon molecule with high n‐type conduction, as a candidate material for the photosensitive layer of LAPS. They report on a peculiar bipolar photo‐response under both reverse and forward biased conditions for C 60 ‐based LAPS. An oxygen‐trap‐induced space‐charge mechanism is proposed to explain the unique bipolar photo‐response phenomenon. The proposed C 60 ‐based LAPS exhibits an excellent pH sensitivity of 150 mV/pH as well as a high spatial resolution of 3.8 µm. The authors anticipate that these results will spark interest in this field and enable the replacement of the inorganic‐semiconductor photosensitive layer by organic semiconductor materials for the construction of high‐performance LAPS.
Photoelectrochemical imaging has great potential in the label-free investigation of cellular processes. Herein, we report a new fast photoelectrochemical imaging system (PEIS) for DC photocurrent imaging of live cells, which combines high speed with excellent lateral resolution and high photocurrent stability, which are all crucial for studying dynamic cellular processes. An analog micromirror was adopted to raster the sensor substrate, enabling high-speed imaging. α-Fe2O3 (hematite) thin films synthesized via electrodeposition were used as a robust substrate with high photocurrent and good spatial resolution. The capabilities of this system were demonstrated by monitoring cell responses to permeabilization with Triton X-100. The ability to carry out dynamic functional imaging of multiple cells simultaneously provides improved confidence in the data than could be achieved with the slower electrochemical single-cell imaging techniques described previously. When monitoring pH changes, the PEIS can achieve frame rates of 8 frames per second.
A novel homogeneous label-free electrochemical biosensor using G-triplex/methylene blue (G3/MB) complex as the signal generator together with an amplification assisted by the λ-exonuclease (λ-Exo) has been successfully constructed for ultrasensitive microRNA (miRNA) detection. An integrated microelectrode was designed to realize the miniaturization of the homogeneous electrochemical assay. Taking advantage of G3, that can specifically bind with MB and decrease its diffusion current, a single-stranded functional DNA hairpin structure was designed as the bio-recognition probe. The probe consisted of G3, eight bases to block G3, and the complementary sequences of the target miRNA. Here we chose miRNA141—a potentially diagnostic biomarker of prostate cancer as the model target. The presence of miRNA141 could hybridize with the probe DNA to form a double-stranded structure with a 5′-phosphorylated terminus. Then λ-Exo was adopted to digest mononucleotides from the 5′-end, leading to the release of G3 part and miRNA141. The released miRNA could hybridize with another probe to trigger the cycling process, while the released G3 could therefore interact with MB to cause a detectable decrease of diffusion current. The proposed strategy showed a low detection limit of 16 fM and an excellent specificity to discriminate single-base mismatches. Furthermore, this sensor was applied to detect miRNA141 from diluted human serum samples, indicating that it has great potential in the application of nucleic acid detection in real samples.
A new photoelectrochemical imaging method termed scanning electrochemical photometric sensor (SEPS) is proposed in this work. It was derived from light-addressable potentiometric sensor (LAPS) and scanning photoinduced impedance microscopy (SPIM) using a front-side laser illumination at a field-effect structure. When the laser beam scans across the sensor substrate, local photocurrent changes at inversion due to the light absorption of analytes can be recorded. It will be shown that SEPS could be used for label-free living cell imaging with micro-resolution as well as real-time quantitative absorption analysis, which would broaden the applications of traditional LAPS/SPIM from potentiometric/impedance measurements to local optical analysis.
Conventional metal oxide semiconductor (MOS) gas sensors have been investigated for decades to protect our life and property. However, the traditional devices can hardly fulfill the requirements of our fast developing mobile society, because the high operating temperatures greatly limit their applications in battery-loaded portable systems that can only drive devices with low power consumption. As ammonia is gaining importance in the production and storage of hydrogen, there is an increasing demand for energy-efficient ammonia detectors. Hence, in this work, a Schottky diode resulting from the contact between zinc oxide nanorods and gold is designed to detect gaseous ammonia at room temperature with a power consumption of 625 μW. The Schottky diode gas sensors benefit from the change of barrier height in different gases as well as the catalytic effect of gold nanoparticles. This diode structure, fabricated without expensive interdigitated electrodes and displaying excellent performance at room temperature, provides a novel method to equip mobile devices with MOS gas sensors.