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1.
ACS Nano ; 18(24): 15332-15357, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38837178

ABSTRACT

Cardiovascular diseases (CVDs) are the leading cause of mortality and therefore pose a significant threat to human health. Cardiac electrophysiology plays a crucial role in the investigation and treatment of CVDs, including arrhythmia. The long-term and accurate detection of electrophysiological activity in cardiomyocytes is essential for advancing cardiology and pharmacology. Regarding the electrophysiological study of cardiac cells, many micronano bioelectric devices and systems have been developed. Such bioelectronic devices possess unique geometric structures of electrodes that enhance quality of electrophysiological signal recording. Though planar multielectrode/multitransistors are widely used for simultaneous multichannel measurement of cell electrophysiological signals, their use for extracellular electrophysiological recording exhibits low signal strength and quality. However, the integration of three-dimensional (3D) multielectrode/multitransistor arrays that use advanced penetration strategies can achieve high-quality intracellular signal recording. This review provides an overview of the manufacturing, geometric structure, and penetration paradigms of 3D micronano devices, as well as their applications for precise drug screening and biomimetic disease modeling. Furthermore, this review also summarizes the current challenges and outlines future directions for the preparation and application of micronano bioelectronic devices, with an aim to promote the development of intracellular electrophysiological platforms and thereby meet the demands of emerging clinical applications.


Subject(s)
Myocytes, Cardiac , Humans , Electrophysiological Phenomena , Animals
2.
Biosens Bioelectron ; 251: 116113, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38364328

ABSTRACT

Autophagy is an important physiological phenomenon in eukaryotes that helps maintain the cellular homeostasis. Autophagy is involved in the development of various cardiovascular diseases, affecting the maintenance of cardiac function and disease prognosis. Physiological levels of autophagy serve as a defense mechanism for cardiomyocytes against environmental stimuli, but an overabundance of autophagy may contribute to the development of cardiovascular diseases. However, conventional biological methods are difficult to monitor the autophagy process in a dynamic and chronic manner. Here, we developed a cardiomyocyte-based biosensing platform that records electrophysiological evolutions in action potentials to reflect the degree of autophagy. Different concentrations of rapamycin-mediated autophagy were administrated in the culture environment to simulate the autophagy model. Moreover, the 3-methyladenine (3-MA)-mediated autophagy inhibition was also investigated the protection on the autophagy. The recorded action potentials can precisely reflect different degrees of autophagy. Our study confirms the possibility of visualizing and characterizing the process of cardiomyocyte autophagy using cardiomyocyte-based biosensing platform, allowing to monitor the whole autophagy process in a non-invasive, real-time, and continuous way. We believe it will pave a promising avenue to precisely study the autophagy-related cardiovascular diseases.


Subject(s)
Biosensing Techniques , Cardiovascular Diseases , Humans , Myocytes, Cardiac , Sirolimus/pharmacology , Autophagy/physiology
3.
Biosens Bioelectron ; 246: 115860, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38039735

ABSTRACT

Action potentials play a pivotal role in diverse cardiovascular physiological mechanisms. A comprehensive understanding of these intricate mechanisms necessitates a high-fidelity intracellular electrophysiological investigative approach. The amalgamation of micro-/nano-electrode arrays and electroporation confers substantial advantages in terms of high-resolution intracellular recording capabilities. Nonetheless, electroporation systems typically lack precise control, and commonly employed electroporation modes, involving tailored sequences, may escalate cellular damage and perturbation of normal physiological functions due to the multiple or higher-intensity electrical pulses. In this study, we developed an innovative electrophysiological biosensing system customized to facilitate precise single-pulse electroporation. This advancement serves to achieve optimal and uninterrupted intracellular action potential recording within cardiomyocytes. The refinement of the single-pulse electroporation technique is realized through the integration of the electroporation and assessment biosensing system, thereby ensuring a consistent and reliable means of achieving stable intracellular access. Our investigation has unveiled that the optimized single-pulse electroporation technique not only maintains robust biosafety standards but also enables the continuous capture of intracellular electrophysiological signals across an expansive three-day period. The universality of this biosensing system, adaptable to various micro/nano devices, furnishes real-time analysis and feedback concerning electroporation efficacy, guaranteeing the sustained, secure, and high-fidelity acquisition of intracellular data, thereby propelling the field of cardiovascular electrophysiological research.


Subject(s)
Biosensing Techniques , Myocytes, Cardiac , Action Potentials/physiology , Myocytes, Cardiac/physiology , Containment of Biohazards , Electroporation
4.
Biosens Bioelectron ; 246: 115832, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38016198

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Biosensing Techniques , Neurodegenerative Diseases , Olfaction Disorders , Humans , Mice , Animals , Alzheimer Disease/metabolism , Mice, Transgenic , Stem Cells/metabolism , Organoids/metabolism , Olfaction Disorders/metabolism , Amyloid beta-Peptides/metabolism
5.
Nano Lett ; 23(24): 11850-11859, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38051785

ABSTRACT

Cardiac oxidative stress is a significant phenotype of myocardial infarction disease, a leading cause of global health threat. There is an urgent need to develop innovative therapies. Nanosized extracellular vesicle (nEV)-based therapy shows promise, yet real-time monitoring of cardiomyocyte responses to nEVs remains a challenge. In this study, a dynamic and label-free cardiomyocyte biosensing system using microelectrode arrays (MEAs) was constructed. Cardiomyocytes were cultured on MEA devices for electrophysiological signal detection and treated with nEVs from E. coli, gardenia, HEK293 cells, and mesenchymal stem cells (MSC), respectively. E. coli-nEVs and gardenia-nEVs induced severe paroxysmal fibrillation, revealing distinct biochemical communication compared to MSC-nEVs. Principal component analysis identified variations and correlations between nEV types. MSC-nEVs enhanced recovery without inducing arrhythmias in a H2O2-induced oxidative stress injury model. This study establishes a fundamental platform for assessing biochemical communication between nEVs and cardiomyocytes, offering new avenues for understanding nEVs' functions in the cardiovascular system.


Subject(s)
Hydrogen Peroxide , Myocytes, Cardiac , Humans , HEK293 Cells , Hydrogen Peroxide/metabolism , Escherichia coli , Arrhythmias, Cardiac , Oxidative Stress
6.
Food Chem ; 429: 136822, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37450994

ABSTRACT

Cyclodextrins, with their unparalleled attributes of eco-friendliness, natural abundance, versatile utility, and facile functionalization, make a paramount contribution to the field of molecular imprinting. Leveraging the unique properties of cyclodextrins in molecularly imprinted polymers synthesis has revolutionized the performance of molecularly imprinted polymers, resulting in enhanced adsorption selectivity, capacity, and rapid extraction of pesticides, while also circumventing conventional limitations. As the concern for food quality and safety continues to grow, the need for standard analytical methods to detect pesticides in food and environmental samples has become paramount. Cyclodextrins, being non-toxic and biodegradable, present an attractive option for greener reagents in imprinting polymers that can also ensure environmental safety post-application. This review provides a comprehensive summary of the significance of cyclodextrins in molecular imprinting for pesticide detection in food and environmental samples. The recent advancements in the synthesis and application of molecularly imprinted polymers using cyclodextrins have been critically analyzed. Furthermore, the current limitations have been meticulously examined, and potential opportunities for greenification with cyclodextrin applications in this field have been discussed. By harnessing the advantages of cyclodextrins in molecular imprinting, it is possible to develop highly selective and efficient methods for detecting pesticides in food and environmental samples while also addressing the challenges of sustainability and environmental impact.


Subject(s)
Cyclodextrins , Molecular Imprinting , Pesticides , Molecularly Imprinted Polymers , Solid Phase Extraction
7.
ACS Sens ; 8(6): 2197-2206, 2023 06 23.
Article in English | MEDLINE | ID: mdl-37303111

ABSTRACT

Abnormal cardiac electrophysiological activities significantly contribute to the incidence of cardiovascular diseases. Therefore, it is crucial to recognize effective drugs, which require an accurate, stable, and sensitive platform. Although conventional extracellular recordings offer a non-invasive and label-free manner to monitor the electrophysiological state of cardiomyocytes, the misrepresented and low-quality extracellular action potentials are difficult to provide accurate and high-content information for drug screening. This study presents the development of a three-dimensional cardiomyocyte-nanobiosensing system that can specifically recognize drug subgroups. The nanopillar-based electrode is manufactured by template synthesis and standard microfabrication technology on a porous polyethylene terephthalate membrane. Based on the cardiomyocyte-nanopillar interface, high-quality intracellular action potentials can be recorded by the minimally invasive electroporation. We validate the performance of a cardiomyocyte-nanopillar-based intracellular electrophysiological biosensing platform by two subclasses of sodium channel blockers, quinidine and lidocaine. The recorded intracellular action potentials accurately reveal the subtle differences between these drugs. Our study indicates that high-content intracellular recordings utilizing nanopillar-based biosensing can provide a promising platform for the electrophysiological and pharmacological investigation of cardiovascular diseases.


Subject(s)
Cardiovascular Diseases , Myocytes, Cardiac , Humans , Lidocaine/pharmacology , Electroporation
8.
Adv Sci (Weinh) ; 10(23): e2207651, 2023 08.
Article in English | MEDLINE | ID: mdl-37310418

ABSTRACT

Chemiluminescence (CL) imaging, as an excitation-free technique, exhibits a markedly improved signal-to-noise ratio (SNR) owing to the absence of an excitation light source and autofluorescence interference. However, conventional chemiluminescence imaging generally focuses on the visible and first near-infrared (NIR-I) regions, which hinders high-performance biological imaging due to strong tissue scattering and absorption. To address the issue, self-luminescent NIR-II CL nanoprobes with a second near-infrared (NIR-II) luminescence in the presence of hydrogen peroxide are rationally designed. A cascade energy transfer, including chemiluminescence resonance energy transfer (CRET) from the chemiluminescent substrate to NIR-I organic molecules and Förster resonance energy transfer (FRET) from NIR-I organic molecules to NIR-II organic molecules, occurs in the nanoprobes, contributing to NIR-II light with great efficiency and good tissue penetration depth. Based on excellent selectivity, high sensitivity to hydrogen peroxide, and long-lasting luminescence performance, the NIR-II CL nanoprobes are applied to detect inflammation in mice, showing a 7.4-fold enhancement in SNR compared with that of fluorescence.


Subject(s)
Luminescence , Nanoparticles , Animals , Mice , Nanoparticles/chemistry , Hydrogen Peroxide , Diagnostic Imaging , Fluorescence
9.
Adv Sci (Weinh) ; 10(7): e2206101, 2023 03.
Article in English | MEDLINE | ID: mdl-36638268

ABSTRACT

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.


Subject(s)
Microphysiological Systems , Taste , Humans , Tongue , Cell Survival , Drug Evaluation, Preclinical
10.
Biosens Bioelectron ; 223: 115034, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36574741

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Receptors, Odorant , Humans , Myocytes, Cardiac , Drug Evaluation, Preclinical , Biomimetics , Smell , Taste , Tachycardia
11.
Biosens Bioelectron ; 216: 114619, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35986984

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Biosensing Techniques , Neurodegenerative Diseases , Olfaction Disorders , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Biomimetics , Dizocilpine Maleate/metabolism , Humans , Memantine/metabolism , Neurons/metabolism , Olfaction Disorders/etiology , Olfaction Disorders/metabolism , Olfaction Disorders/pathology , Olfactory Bulb , Smell
12.
Anal Chem ; 94(19): 6976-6985, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35503097

ABSTRACT

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.


Subject(s)
Sweetening Agents , Taste , Animals , Mammals , Taste/physiology , Tongue
13.
Adv Healthc Mater ; 11(3): e2100934, 2022 02.
Article in English | MEDLINE | ID: mdl-34648692

ABSTRACT

Tissue engineering techniques have enabled to replicate the geometrical architecture of native tissues but usually fail to reproduce their exact cellular arrangements during the fabricating process, while it is critical for manufacturing physiologically relevant tissues. To address this problem, a "sewing-like" method of controlling cellular alignment during the fabricating process is reported here. By integrating the stretching step into the fabricating process, a static mechanical environment is created which, in turn, regulates the subsequent cellular alignment, elongation, and differentiation in the generated tissues. With this method, patterned cellular constructs can be fabricated with controlled cellular alignment. Moreover, this method shows a potent capability to fabricate physiologically relevant skeletal muscle constructs in vitro by mechanically inducing myoblast fusion and maturation. As a potential clinical application, aligned myofibers are directly fabricated onto injured muscles in vivo, which repair the damaged tissues effectively. This study shows that the "sewing-like" method can produce engineered tissues with precise control of cellular arrangements and more clinically viable functionalities.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Muscle, Skeletal , Tissue Engineering/methods
14.
Analyst ; 147(1): 178-186, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34870643

ABSTRACT

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.


Subject(s)
Odorants , Olfactory Bulb , Animals , Rats , T-Lymphocytes
15.
ACS Sens ; 6(7): 2593-2604, 2021 07 23.
Article in English | MEDLINE | ID: mdl-34253023

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Taste , Animals , Cardiotoxicity , Myocytes, Cardiac , Receptors, G-Protein-Coupled
16.
Anal Chim Acta ; 1162: 338452, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-33926702

ABSTRACT

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.


Subject(s)
Anti-Asthmatic Agents , Animals , Anti-Asthmatic Agents/pharmacology , Biomimetics , Electric Impedance , Electronics , Mice , Muscle, Smooth , Myocytes, Smooth Muscle , Receptors, G-Protein-Coupled , Reproducibility of Results , Respiratory System
17.
Biosens Bioelectron ; 171: 112737, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33080464

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Odorants , Animals , Microelectrodes , Smell
18.
Biosens Bioelectron ; 145: 111673, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31546200

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Electronic Nose , Quaternary Ammonium Compounds/isolation & purification , Sodium Glutamate/isolation & purification , Animals , Bionics/trends , Myocytes, Cardiac/metabolism , Quaternary Ammonium Compounds/chemistry , Rats , Receptors, G-Protein-Coupled/genetics , Sodium Glutamate/chemistry , Taste/genetics , Taste Buds/chemistry
19.
Talanta ; 199: 131-139, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30952236

ABSTRACT

Detection and identification of bitter compounds draw great attention in pharmaceutical and food industry. Several well-known agonists of specific bitter taste receptors have been found to exhibit anti-cancer effects. For example, N-C=S-containing compounds, such as allyl-isothiocyanates, have shown cancer chemo-preventive effects. It is worth noting that human T2R38 receptor is specific for compounds containing N-C=S moiety. Here, a bioinspired cell-based bioelctronic tongue (BioET) is developed for the high-specificity isothiocyanate-induced bitter detection, utilizing human Caco-2 cells as a primary sensing element and interdigitated impedance sensor as a secondary transducer. As an intestinal carcinoma cell line, Caco-2 endogenously expresses human bitter receptor T2R38, and the activation of T2R38 induces the changes of cellular morphology which can be detected by electric cell-substrate impedance sensing (ECIS). After configuration and optimization of parameters including timing of compound administration and cell density, quantitative bitter evaluation models were built for two well-known bitter compounds, phenylthiocarbamide (PTC) and propylthiouracil (PROP). The bitter specific detection of this BioET is inhibited by probenecid and U-73122, and is not elicited by other taste modalities or bitter ligands that do not activate T2R38. Moreover, by combining different computational tools, we designed a ligand-based virtual screening (LBVS) protocol to select ligands that are likely to activate T2R38 receptor. Three computationally predicted agonists of T2R38 were selected using the LBVS protocol, and the BioET presented response to the predicted agonists, validating the capability of the LBVS protocol. This study suggests this unique cell-based BioET paves a general and promising way to specifically detect N-C=S-containing compounds that can be used for pharmaceutical study and drug development.


Subject(s)
Electronic Nose , Isothiocyanates/analysis , Receptors, G-Protein-Coupled/metabolism , Caco-2 Cells , Dose-Response Relationship, Drug , Humans , Isothiocyanates/pharmacology , Ligands , Molecular Structure , Phenylthiourea/chemistry , Phenylthiourea/pharmacology , Propylthiouracil/chemistry , Propylthiouracil/pharmacology , Receptors, G-Protein-Coupled/agonists , Structure-Activity Relationship , Tumor Cells, Cultured
20.
J Neurosci Methods ; 307: 221-229, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29859214

ABSTRACT

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".


Subject(s)
Brain-Computer Interfaces , Evoked Potentials, Somatosensory/physiology , Motion , Olfactory Pathways/physiology , Smell/physiology , Wearable Electronic Devices , Action Potentials/physiology , Animals , Conditioning, Operant , Electric Stimulation , Electroencephalography , Male , Microelectrodes , Olfactory Pathways/cytology , Rats , Rats, Sprague-Dawley , Sensory Receptor Cells/physiology
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