Patterning Techniques Based on Metallized Electrospun Nanofibers for Advanced Stretchable Electronics.

Stretchable electronics have experienced remarkable progress, especially in sensors and wireless communication systems, attributed to their ability to conformably contact with rough or uneven surfaces. However, the development of complex, multifunctional, and high-precision stretchable electronics faces substantial challenges, including instability at rigid-soft interfaces and incompatibility with traditional high-precision patterning technologies. Metallized electrospun nanofibers emerge as a promising conductive filler, offering exceptional stretchability, electrical conductivity, transparency, and compatibility with existing patterning technologies. Here, this review focuses on the fundamental properties, preparation processes, patterning technologies, and application scenarios of conductive stretchable composites based on metallized nanofibers. Initially, it introduces the fabrication processes of metallized electrospun nanofibers and their advantages over alternative materials. It then highlights recent progress in patterning technologies, including collector collection, vapor deposition with masks, and lithography, emphasizing their role in enhancing precision and integration. Furthermore, the review shows the broad applicability and potential influence of metallized electrospun nanofibers in various fields through their use in sensors, wireless systems, semiconductor devices, and intelligent healthcare solutions. Ultimately, this review seeks to spark further innovation and address the prevailing challenges in stretchable electronics, paving the way for future breakthroughs in this dynamic field.

Multimodal spatiotemporal monitoring of basal stem cell-derived organoids reveals progression of olfactory dysfunction in Alzheimer's disease.

Olfactory dysfunction (OD) is a highly prevalent symptom and an early sign of neurodegenerative diseases in humans. However, the roles of peripheral olfactory system in disease progression and the mechanisms behind neurodegeneration remain to be studied. Olfactory epithelium (OE) organoid is an ideal model to study pathophysiology in vitro, yet the reliance on 3D culture condition limits continual in situ monitoring of organoid development. Here, we combined impedance biosensors and live imaging for real-time spatiotemporal analysis of OE organoids morphological and physiological features during Alzheimer's disease (AD) progression. The impedance measurements showed that organoids generated from basal stem cells of APP/PS1 transgenic mice had lower proliferation rate than that from wild-type mice. In concert with the biosensor measurements, live imaging enabled to visualize the spatial and temporal dynamics of organoid morphology. Abnormal protein aggregation and accumulation, including amyloid plaques and neurofibrillary tangles, was found in AD organoids and increased as disease progressed. This multimodal in situ bioelectrical measurement and imaging provide a new platform for investigating onset mechanisms of OD, which would shed new light on early diagnosis and treatment of neurodegenerative disease.

Long-Term Flexible Neural Interface for Synchronous Recording of Cross-Regional Sensory Processing along the Olfactory Pathway.

Humans perceive the world through five senses, of which olfaction is the oldest evolutionary sense that enables the detection of chemicals in the external environment. Recent progress in bioinspired electronics has boosted the development of artificial sensory systems. Here, a biohybrid olfactory system is proposed by integrating living mammals with implantable flexible neural electrodes, to employ the outstanding properties of mammalian olfactory system. In olfactory perception, the peripheral organ-olfactory epithelium (OE) projects axons into the olfactory relay station-olfactory bulb (OB). The olfactory information encoded in the neural activity is recorded from both OE and OB simultaneously using flexible neural electrodes. Results reveal that spontaneous slow oscillations (<12 Hz) in both OE and OB closely follow respiration. This respiration-locked rhythm modulates the amplitude of fast oscillations (>20 Hz), which are associated with odor perception. Further, by extracting the characteristics of odor-evoked oscillatory signals, responses of different odors are identified and classified with 80% accuracy. This study demonstrates for the first time that the flexible electrode enables chronic stable electrophysiological recordings of the peripheral and central olfactory system in vivo. Overall, the method provides a novel neural interface for olfactory biosensing and cognitive processing.

Mimicking the Biological Sense of Taste In Vitro Using a Taste Organoids-on-a-Chip System.

Thanks to the gustatory system, humans can experience the flavors in foods and drinks while avoiding the intake of some harmful substances. Although great advances in the fields of biotechnology, microfluidics, and nanotechnologies have been made in recent years, this astonishing recognition system can hardly be replaced by any artificial sensors designed so far. Here, taste organoids are coupled with an extracellular potential sensor array to form a novel bioelectronic organoid and developed a taste organoids-on-a-chip system (TOS) for highly mimicking the biological sense of taste ex vivo with high stability and repeatability. The taste organoids maintain key taste receptors expression after the third passage and high cell viability during 7 days of on-chip culture. Most importantly, the TOS not only distinguishs sour, sweet, bitter, and salt stimuli with great specificity, but also recognizes varying concentrations of the stimuli through an analytical method based on the extraction of signal features and principal component analysis. It is hoped that this bioelectronic tongue can facilitate studies in food quality controls, disease modelling, and drug screening.

Biomimetic integrated gustatory and olfactory sensing array based on HL-1 cardiomyocyte facilitating drug screening for tachycardia treatment.

The ectopic co-expression of taste and olfactory receptors in cardiomyocytes provides not only possibilities for the construction of biomimetic gustatory and olfactory sensors but also promising novel therapeutic targets for tachycardia treatment. Here, bitter taste and olfactory receptors endogenously expressed in HL-1 cells were verified by RT-PCR and immunofluorescence staining. Then HL-1 cardiomyocyte-based integrated gustatory and olfactory sensing array coupling with the microelectrode array (MEA) was first constructed for drugs screening and evaluation for tachycardia treatment. The MEA sensor detected the extracellular field potentials and reflected the systolic-diastolic properties of cardiomyocytes in real time in a label-free and non-invasive way. The in vitro tachycardia model was constructed using isoproterenol as the stimulator. The proposed sensing array facilitated potential drug screening for tachycardia treatment, such as salicin, artemisinin, xanthotoxin, and azelaic acid which all activated specific receptors on HL-1 cells. IC50 values for four potential drugs were calculated to be 0.0036 µM, 309.8 µM, 14.68 µM, and 0.102 µM, respectively. Visualization analysis with heatmaps and PCA cluster showed that different taste and odorous drugs could be easily distinguished. The mean inter-class Euclidean distance between different bitter drugs was 1.681, which was smaller than the distance between bitter and odorous drugs of 2.764. And the inter-class distance was significantly higher than the mean intra-class Euclidean distance of 1.172. In summary, this study not only indicates a new path for constructing novel integrated gustatory and olfactory sensors but also provides a powerful tool for the quantitative evaluation of potential drugs for tachycardia treatment.

Neuronal network-based biomimetic chip for long-term detection of olfactory dysfunction model in early-stage Alzheimer's disease.

Olfactory dysfunction is an early symptom of neurodegenerative disease. Amyloid-beta oligomers (AßOs), the pathologic protein of Alzheimer's disease (AD), have been confirmed to be firstly deposited in olfactory bulb (OB), causing smell to malfunction. However, the detailed mechanisms underlying pathogenic nature of AßOs-induced olfactory neuronal degeneration in AD are not completely realized. Here, an early-stage olfactory dysfunction pathological model of AD in vitro based on biomimetic OB neuronal network chip was established for dynamic multi-site detection of neuronal electrical activity and network connection. We found both spike firing and correlation of overall neuronal network change regularly displayed gradually active state and then rapidly decay state after AßOs induction. Moreover, MK-801 and memantine were administrated at early-stage to detect alteration of OB neurons simulating nasal administration for AD treatment, which showed an almost recovery through the intermittent firing pattern. Together, this neuronal network-on-chip has revealed synaptic impairment and network neurodegeneration of olfactory dysfunction in AD, providing potential mechanisms information for early-stage progressive olfactory amyloidogenic pathology.

Biohybrid Tongue for Evaluation of Taste Interaction between Sweetness and Sourness.

The past decade has witnessed tremendous progress achieved in taste research, while few studies focus on interactions among taste compounds. Indeed, sweeteners and acidulants are commonly used food additives, and sweet-sour mixtures always provide improved tastes. For example, sensory studies have shown that sourness suppresses sweetness. However, the degree of sweetness suppression by sourness is difficult to evaluate quantitatively and objectively. Therefore, we propose a biohybrid tongue that is constructed by integrating mammalian gustatory epithelium with a microelectrode array chip. The taste quality and intensity information is coded in time-frequency patterns of local field potential. Different response patterns evoked by sweet and sour stimuli are observed, and the response is dose-dependent. Then, interaction effects of sourness against sweetness are quantified. The results indicate that suppression of sweetness by sourness occurs by increasing sourness concentrations. In summary, this study provides a powerful new tool for quantitative evaluation of sweet, sour, and their binary taste interactions that mimic the mammalian taste system.

An in vivo bioelectronic nose for possible quantitative evaluation of odor masking using M/T cell spatial response patterns.

Odor masking is a prominent phenomenon in the biological olfactory perception system. It has been applied in industry and daily life to develop masking agents to reduce or even eliminate the adverse effects of unpleasant odors. However, it is challenging to assess the odor masking efficiency with traditional gas sensors. Here, we took advantage of the olfactory perception system of an animal to develop a system for the evaluation and quantification of odor masking based on an in vivo bioelectronic nose. The linear decomposition method was used to extract the features of the spatial response pattern of the mitral/tufted (M/T) cell population of the olfactory bulb of a rat to monomolecular odorants and their binary mixtures. Finally, the masking intensity was calculated to quantitatively measure the degree of interference of one odor to another in the biological olfactory system. Compared with the human sensory evaluation reported in a previous study, the trend of masking intensity obtained with this system positively correlated with the human olfactory system. The system could quantitatively analyze the masking efficiency of masking agents, as well as assist in the development of new masking agents or flavored food in odor or food companies.

Hybrid Integrated Cardiomyocyte Biosensors for Bitter Detection and Cardiotoxicity Assessment.

Among basic taste sensations, bitter taste is vital to the survival of mammals due to its indispensable role in toxin prediction or identification, so the identification of bitter compounds is of great value in the pharmaceutical and food industry. Recently, bitter taste receptor (T2Rs)-based biosensors have been developed for specific bitter detection. However, the taste biosensors based on taste cells/tissues suffer from simple function, low sensitivity, low content, and limited parameters. Here, to establish a high-content, highly sensitive, and multifunctional taste biosensor, we developed a multifunctional hybrid integrated cardiomyocyte biosensor (HICB) for bitter detection. Due to the expression of bitter taste receptors in cardiomyocytes, the HICB can recognize the specific bitter agonists by synchronously recording the extracellular field potential (EFP) and mechanical beating (MB) signals from the cultured cardiomyocytes in vitro. Multiple feature parameters were defined and extracted from the electromechanical signals of cardiomyocytes to analyze the specific responses to four typical bitter compounds. The radar map, heat map, and principal component analysis (PCA) were used to visualize and classify the specific responses. Moreover, bitter-induced cardiotoxicity also was chronically evaluated, and these bitter compounds presented an inhibition effect on the electrophysiological and contractile activities of cardiomyocytes. This high-content HICB offers an alternative platform for both bitter detection and cardiotoxicity assessment, showing promising applications in the fields of taste detection and toxicity screening.

Biomimetic in vitro respiratory system using smooth muscle cells on ECIS chips for anti-asthma TCMs screening.

Airway smooth muscle (ASM) contraction is a major pathophysiological characteristic of asthma. Although ß2-adrenoceptor (ß2-AR) agonists are currently used as bronchodilators, they cause rapid effect and long-term agonist-induced desensitization. Thus, it is necessary to search for more effective and safer relaxant agents for ASM cells. In this work, bitter taste receptors (TAS2Rs) were demonstrated to be expressed in primary mouse ASM cells endogenously, and they were considered as new drug targets for asthma treatment. Traditional Chinese medicines (TCMs) contained a wide range of TAS2R agonists and some of them had the efficacy of relieving cough and asthma with less toxic side effects. Then the electronic cell-substrate impedance sensor (ECIS) was used for the first time to establish a method to detect the contraction/relaxation effects of ASM cells. Therefore, we introduced a biomimetic in vitro respiratory system using ASM cells on ECIS chips to screen for potential TCMs against asthma. Quinine, nobiletin, and picfeltarraenin IA screened in this study could effectively inhibit the ASM contraction in a concentration-dependent manner, showing potential value as novel anti-asthma drugs. Furthermore, the effective screening of anti-asthma drugs was realized based on 3D ASM cell arrays and gel imaging system. Consistent results were found and the reliability of the biomimetic in vitro respiratory system for the screening of TCMs against asthma was further verified. The biomimetic system designed in this study has the advantages of operation simplicity, high throughput, non-invasive, real-time, and high sensitivity, and therefore provides a promising drug screening platform for asthma disease.

A Review of Recent Advances in Flexible Wearable Sensors for Wound Detection Based on Optical and Electrical Sensing.

Chronic wounds that are difficult to heal can cause persistent physical pain and significant medical costs for millions of patients each year. However, traditional wound care methods based on passive bandages cannot accurately assess the wound and may cause secondary damage during frequent replacement. With advances in materials science and smart sensing technology, flexible wearable sensors for wound condition assessment have been developed that can accurately detect physiological markers in wounds and provide the necessary information for treatment decisions. The sensors can implement the sensing of biochemical markers and physical parameters that can reflect the infection and healing process of the wound, as well as transmit vital physiological information to the mobile device through optical or electrical signals. Most reviews focused on the applicability of flexible composites in the wound environment or drug delivery devices. This paper summarizes typical biochemical markers and physical parameters in wounds and their physiological significance, reviews recent advances in flexible wearable sensors for wound detection based on optical and electrical sensing principles in the last 5 years, and discusses the challenges faced and future development. This paper provides a comprehensive overview for researchers in the development of flexible wearable sensors for wound detection.

A biohybrid nose for evaluation of odor masking in the peripheral olfactory system.

Olfaction is a synthetic sense in which odor mixtures elicit emergent perceptions at the expense of perceiving the individual components. The most common result of mixing two odors is masking one component by another. However, there is lack of analytical techniques for measuring the sense of smell, which is mediated by cross-odorant interactions. Here, we propose a biohybrid nose for objective and quantitative evaluation of malodor masking efficiency of perfumed products. This biohybrid nose is constructed by integrating mammalian olfactory epithelium with microelectrode array chip to read out the olfactory information as electrical signal from multiple tissue sites. The intrinsic odor response of olfactory epithelium is found to be represented by widespread spatiotemporal oscillatory activity. The masking efficiency of fragrance is quantified by calculating the relative difference between the malodor and the binary mixture (malodor + fragrance) response patterns. Results indicate that masking efficiency of fragrance is concentration-dependent, whereas completely masking may occurs when fragrance is employed at a concentration 2-3 orders of magnitude higher than malodor. This study demonstrates for the first time that capitalizing on the biological sense of smell to create biohybrid system provides an effective technique to resolve more complex biosensing-related issues such as odor interactions in mixtures.

A novel bionic in vitro bioelectronic tongue based on cardiomyocytes and microelectrode array for bitter and umami detection.

Electronic tongues (ETs) have been developed and widely used in food, beverage and pharmaceutical fields, but limited in sensitivity and specificity. In recent years, bioelectronic tongues (BioETs) integrating biological materials and various types of transducers are proposed to bridge the gap between ET system and biological taste. In this work, a bionic in vitro cell-based BioET is developed for bitter and umami detection, utilizing rat cardiomyocytes as a primary taste sensing element and microelectrode arrays (MEAs) as a secondary transducer for the first time. The primary cardiomyocytes of Sprague Dawley (SD) rats, which endogenously express bitter and umami taste receptors, were cultured on MEAs. Cells attached and grew well on the sensor surface, and syncytium was formed for potential conduction and mechanical beating, indicating the good biocompatibility of surface coating. The specificity of this BioET was verified by testing different tastants and bitter compounds. The results show that the BioET responds to bitter and umami compounds specifically among five basic tastants. For bitter recognition, only those can activate receptors in cardiomyocytes can be recognized by the BioET, and different bitter substances could be discriminated by principal component analysis (PCA). Moreover, the specific detections of two bitters (Denatonium Benzoate, Diphenidol) and an umami compound (Monosodium Glutamate) were realized with a detection limit of 10-6 M. The cardiomyocytes-based BioET proposed in this work provides a new approach for the construction of BioETs and has promising applications in taste detection and pharmaceutical study.

A wearable system for olfactory electrophysiological recording and animal motion control.

BACKGROUND: Bran-computer interface (BCI) is an important technique used in brain science. However, the large size of equipment and wires severely limit its practical applications. NEW METHODS: This study presents a wearable system with bidirectional brain-computer interface based on Wi-Fi technology, which can be used for olfactory electrophysiological recording and animal motion control. RESULTS: On the "brain-to-computer" side, the results show that the wireless system can record high-quality olfactory electrophysiological signals for over a month. By analyzing the recorded data, we find that the same mitral/tufted (M/T) cells can be activated by many odorants and different M/T cells can be activated by a single odorant. Further, we find neurons in dorsal lateral OB are highly sensitive to isoamyl acetate. On the "computer-to-brain" side, the results show that we can efficiently control rats' motions by applying electrical stimulations to electrodes implanted in specific brain regions. COMPARISON WITH EXISTING METHODS: Most existing wireless BCI systems are designed for either recording or stimulating while our system is a bidirectional BCI featured with both functions. Taking advantage of our years of experience in olfactory decoding, we developed the first wireless system for olfactory electrophysiological recording and animal motion control. It provides high-quality recording and efficient motion control for a long time. CONCLUSIONS: The system provides possibility of practical BCI applications, such as in vivo bioelectronic nose and "rat-robot".