Recent advances in the development of bioelectronic nose

The olfactory system has the ability to discriminate and identify thousands of odorant compounds at very low concentrations. Recently, many researchers have been trying to develop artificial sensing devices that are based on the olfactory system. A bioelectronic nose, which uses olfactory receptors (ORs) as sensing elements, would benefit naturally optimized molecular recognition. Accordingly, ORs can be effectively used as a biological element in bioelectronic noses. Bioelectronic nose can be classified into cell-based and protein-based biosensors. The cell-based biosensor uses living cells that express olfactory receptors as the biological sensing elements and the protein-based biosensor uses the olfactory receptor protein. The binding of odorant molecules to the ORs can be measured using various methods such as piezoelectric, optic, and electric devices. Thus, bioelectronic nose can be developed by combining the biological sensing elements with these non-biological devices. The application of bioelectronic nose in a wide range of different scientific and medical fields is essentially dependent on the development of highly sensitive and selective biosensors. These sensor systems for the rapid detection of specific odorants are crucial for environmental monitoring, anti-bioterrorism, disease diagnostics, and food safety. In this article, we reviewed recent advances in the development of bioelectronic nose.     

The bioelectronic nose and tongue using olfactory and taste receptors: Analytical tools for food quality and safety assessment

Food intake is the primary method for obtaining energy and component materials in the human being. Humans evaluate the quality of food by combining various facets of information, such as an item of food's appearance, smell, taste, and texture in the mouth. Recently, bioelectronic noses and tongues have been reported that use human olfactory and taste receptors as primary recognition elements, and nanoelectronics as secondary signal transducers. Bioelectronic sensors that mimic human olfaction and gustation have sensitively and selectively detected odor and taste molecules from various food samples, and have been applied to food quality assessment. The portable and multiplexed bioelectronic nose and tongue are expected to be used as next-generation analytical tools for rapid on-site monitoring of food quality. In this review, we summarize recent progress in the bioelectronic nose and tongue using olfactory and taste receptors, and discuss the potential applications and future perspectives in the food industry.     

Nanovesicle-based bioelectronic nose platform mimicking human olfactory signal transduction

We developed a nanovesicle-based bioelectronic nose (NBN) that could recognize a specific odorant and mimic the receptor-mediated signal transmission of human olfactory systems. To build an NBN, we combined a single-walled carbon nanotube-based field effect transistor with cell-derived nanovesicles containing human olfactory receptors and calcium ion signal pathways. Importantly, the NBN took advantages of cell signal pathways for sensing signal amplification, enabling ≈ 100 times better sensitivity than that of previous bioelectronic noses based on only olfactory receptor protein and carbon nanotube transistors. The NBN sensors exhibited a human-like selectivity with single-carbon-atomic resolution and a high sensitivity of 1 fM detection limit. Moreover, this sensor platform could mimic a receptor-meditated cellular signal transmission in live cells. This sensor platform can be utilized for the study of molecular recognition and biological processes occurring at cell membranes and also for various practical applications such as food screening and medical diagnostics.     

Olfactory receptor cells respond to odors in a tissue and semiconductor hybrid neuron chip

Olfactory systems of human beings and animals have the abilities to sense and distinguish varieties of odors. In this study, a bioelectronic nose was constructed by fixing biological tissues onto the surface of light-addressable potentiometric sensor (LAPS) to mimic human olfaction and realize odor differentiation. The odorant induced potentials on tissue-semiconductor interface was analyzed by sensory transduction theory and sheet conductor model. The extracellular potentials of the receptor cells in the olfactory epithelium were detected by LAPS. Being stimulated by different odorants, such as acetic acid and butanedione, olfactory epithelium activities were analyzed on basis of local field potentials and presented different firing modes. The signals fired in different odorants could be distinguished into different clusters by principal component analysis (PCA). Therefore, with cellular populations well preserved, the epithelium tissue and LAPS hybrid system will be a promising neuron chip of olfactory biosensors for odor detecting.     

Bioelectronic nose with high sensitivity and selectivity using chemically functionalized carbon nanotube combined with human olfactory receptor

Single-walled carbon nanotubes (swCNTs) hold great promise for use as molecular wires because they exhibit high electrical conductivity and chemical stability. However, constructing swCNT-based transducer devices requires controlled strategies for assembling biomolecules on swCNTs. In this study, we proposed a chemically modified swCNT. The swCNT was functionalized with 1,5-diaminonaphthalene via π-stacking, for reliable attachment of the human olfactory receptor 2AG1 (hOR2AG1). The human olfactory receptor was then anchored. We investigated the use of this functionalized CNT in the fabrication of a highly sensitive and selective bioelectronic nose. For the bioelectronic nose, the swCNT-field effect transistor (FET) platform was composed of polyethylene glycol (PEG)-coated regions to prevent non-specific absorption and chemically modified swCNTs regions containing hOR2AG1, which can bind to the specific odorant. This approach allowed us to create well-defined micron-scale patterns of hOR2AG1 on the swCNTs. Our bioelectronic nose displayed ultrahigh sensitivity down to concentrations as low as 1fM due to the enhanced hOR2AG1-odorant interaction through the tight binding of hOR2AG1 on the chemically modified swCNTs. In addition, the approach described here may provide an alternative route for multiplexed detection of diverse odorants and to improve the sensitivity of sensor devices.     

Olfactory cell-based biosensor: a first step towards a neurochip of bioelectronic nose

Human olfactory system can distinguish thousands of odors. In order to realize the biomimetic design of electronic nose on the principle of mammalian olfactory system, this article reports an olfactory cell-based biosensor as a real bionic technique for odorants detection. Effective cultures of olfactory receptor neurons and olfactory bulb cells have been achieved on the semiconductor chip. Using light-addressable potentiometric sensor (LAPS) as sensing chip to monitor extracellular potential of the neurons, the response under stimulations of the odorants or neurotransmitters, such as acetic acid and glutamic acid, was tested. The results demonstrate that this kind of hybrid system of LAPS and olfactory neurons, which is sensitive to odorous changes, has great potential and is promising to be used as a novel neurochip of bioelectronic nose for detecting odors.     

FET-based nanobiosensors for the detection of smell and taste

Various nanobiosensors composed of biomaterials and nanomaterials have been developed, due to their demonstrated advantage of showing high performance. Among various biomaterials for biological recognition elements of the nanobiosensor, sensory receptors, such as olfactory and taste receptors, are promising biomaterials for developing nanobiosensors, because of their high selectivity to target molecules. Field-effect transistors(FET) with nanomaterials such as carbon nanotube(CNT), graphene, and conducting polymer nanotube(CPNT), can be combined with the biomaterials to enhance the sensitivity of nanobiosensors.Recently, many efforts have been made to develop nanobiosensors using biomaterials, such as olfactory receptors and taste receptors for detecting various smells and tastes. This review focuses on the biomaterials and nanomaterials used in nanobiosensor systems and studies of various types of nanobiosensor platforms that utilize olfactory receptors and taste receptors which could be applied to a wide range of industrial fields, including the food and beverage industry, environmental monitoring, the biomedical field, and anti-terrorism.     

Heterogeneity of molecular mechanisms the olfactor reception

In experiments on the frog isolated olfactory epithelium by using vital fluorescent microscope, odorants with fruit, rank, flower and camphor smell were shown to involve intracellular signaling systems in olfactory transduction. The odorants with different qualitative smells have different messenger and activity mechanisms. Intracellular messengers do not participate in reception of odorants with piquant and rotten smells. Thus the perception of different odour substances is maintained by physical and chemical processes. Hence, not only taste, carotid, medullar, but olfactory reception as well are characterised by heterogeneity of biophysical mechanisms.     

Morituri te salutant? Olfactory signal transduction and the role of phosphoinositides

During the past 150 years, researchers have investigated the cellular, physiological, and molecular mechanisms underlying the sense of smell. Based on these efforts, a conclusive model of olfactory signal transduction in the vertebrate's nose is now available, spanning from G-protein-mediated odorant receptors to ion channels, which are linked by a cyclic adenosine 3',5'-monophosphate-mediated signal transduction cascade. Here we review some historical milestones in the chronology of olfactory research, particularly emphasising the role of cyclic nucleotides and inositol trisphosphate as alternative second messengers in olfactory cells. We will describe the functional anatomy of the nose, outline the cellular composition of the olfactory epithelium, and describe the discovery of the molecular backbone of the olfactory signal transduction cascade. We then summarize our current model, in which cyclic adenosine monophosphate is the sole excitatory second messenger in olfactory sensory neurons. Finally, a possible significance of microvillous olfactory epithelial cells and inositol trisphosphate in olfaction will be discussed.     

Nanobiohybrid Material‐Based Bioelectronic Devices

Biomolecules, especially proteins and nucleic acids, have been widely studied to develop biochips for various applications in scientific fields ranging from bioelectronics to stem cell research. However, restrictions exist due to the inherent characteristics of biomolecules, such as instability and the constraint of granting the functionality to the biochip. Introduction of functional nanomaterials, recently being researched and developed, to biomolecules have been widely researched to develop the nanobiohybrid materials because such materials have the potential to enhance and extend the function of biomolecules on a biochip. The potential for applying nanobiohybrid materials is especially high in the field of bioelectronics. Research in bioelectronics is aimed at realizing electronic functions using the inherent properties of biomolecules. To achieve this, various biomolecules possessing unique properties have been combined with novel nanomaterials to develop bioelectronic devices such as highly sensitive electrochemical‐based bioelectronic sensing platforms, logic gates, and biocomputing systems. In this review, recently reported bioelectronic devices based on nanobiohybrid materials are discussed. The authors believe that this review will suggest innovative and creative directions to develop the next generation of multifunctional bioelectronic devices.     

How much does nasal cavity morphology matter? Patterns and rates of olfactory airflow in phyllostomid bats

The morphology of the nasal cavity in mammals with a good sense of smell includes features that are thought to improve olfactory airflow, such as a dorsal conduit that delivers odours quickly to the olfactory mucosa, an enlarged olfactory recess at the back of the airway, and a clear separation of the olfactory and respiratory regions of the nose. The link between these features and having a good sense of smell has been established by functional examinations of a handful of distantly related mammalian species. In this paper, we provide the first detailed examination of olfactory airflow in a group of closely related species that nevertheless vary in their sense of smell. We study six species of phyllostomid bats that have different airway morphologies and foraging ecologies, which have been linked to differences in olfactory ability or reliance. We hypothesize that differences in morphology correlate with differences in the patterns and rates of airflow, which in turn are consistent with dietary differences. To compare species, we make qualitative and quantitative comparisons of the patterns and rates of airflow through the olfactory region during both inhalation and exhalation across the six species. Contrary to our expectations, we find no clear differences among species in either the patterns of airflow through the airway or in rates of flow through the olfactory region. By and large, olfactory airflow seems to be conserved across species, suggesting that morphological differences appear to be driven by other mechanical demands on the snout, such as breathing and feeding. Olfactory ability may depend on other aspects of the system, such as the neurobiological processing of odours that work within the existing morphology imposed by other functional demands on the nasal cavity.     

Odorant receptor genes in humans.

The sense of smell is highly sophisticated in vertebrates but Homo sapiens ranks low in olfactory performance when compared to other species - why? Olfaction initiates with the interaction of odorants with specific receptors on the surface of olfactory sensory neurons in the nose. The genes encoding odorant receptors form the largest family in the vertebrate genome, numbering as many as 1000 in rodents. It has recently come to light that the repertoire of human odorant receptor genes, unlike in other vertebrates, is riddled with pseudogenes.     

Assessment of solid state fermentation by a biolectronic artificial nose

The use of a bioelectronic artificial nose (AN) is described for on-site-monitoring to assess the reaction patterns of solid state fermentations for control of microclimate at sampling site. The nose consists of fractionated olfactory cell proteins of bullfrog (as a receptor membrane) coated on a piezoelectric quartz crystal connected to an oscillator and a data recorder with a personal computer (PC). Five fractions of the olfactory cell proteins gave 5 probes. The response of the nose was analyzed by the PC either as profiles to show the kinds of doors, or as scale factors to show the intensity of odours. Definite differences were noted between the profiles of the headspace gases from earlier and later stages of composing of solid hog wastes. The scale factors showed a single large peak in the earlier stage and one small peak in the later stage. The former showed vigorous biodegradation of organic matter and the latter indicated stabilization of the finished compost. In addition to its use in composing, the nose can discriminate various kinds of alcoholic beverages.     

综述与专论: 纳米酶及其细胞活性氧调控

随着纳米技术的不断进步,人们逐渐开发出能够模拟天然抗氧化酶催化活性的无机纳米材料．这些纳米材料能够模拟过氧化物酶、过氧化氢酶、超氧化物歧化酶等天然酶的催化过程,从而调控细胞的氧化还原水平．本文从金属化合物、贵金属以及碳基纳米酶的角度,阐述了它们对细胞内活性氧(ROS)的调控作用以及在各种氧化应激相关疾病治疗中的应用．作为一种新型的模拟酶,纳米酶有望在生物医学领域中为疾病治疗提供一种新的策略．     

Functional organization of a neural network for aversive olfactory learning in Caenorhabditis elegans

Many animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of Caenorhabditis elegans for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference. Calcium imaging and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory sensory neurons into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.     

NEURAL METHODS OF CALIBRATION OF SENSORS FOR GAS MEASUREMENTS AND AROMA IDENTIFICATION SYSTEM

The article presents the neural methods of calibration of gas sensors for use in an artificial electronic nose for gas measurements. Different neural network solutions will be presented and compared. They include the classical multilayer perceptron, neuro-fuzzy networks and support vector machines. The other aspect illustrated in the article is the introductory preprocessing of the measured sensor signals in order to attain the highest possible efficiency of the gas measuring system. The theoretical considerations will be supported by the numerical experiments concerning the application of the electronic nose. The first practical aspect is concerned with the application of the developed system for classification problems and will be illustrated in the examples of the recognition of the biocomponents in the gasoline and the recognition of smells of cosmetic cream at the aging process. The second one belongs to the estimation problem and is concerned with the determination of the concentration of the particular gas components in the mixture of gases.

PRACTICAL APPLICATIONS

The results presented in the article may find practical application for calibration of the electronic nose in gas measurements. The electronic nose is widely used for smell recognition. It may find practical application in the petroleum, cosmetics or food industry for the assessment of the quality of their products. Military application is also of great interest.     

Searching for the Ligands of Odorant Receptors

Through the sense of smell mammals can detect and discriminate between a large variety of odorants present in the surrounding environment. Odorants bind to a large repertoire of odorant receptors located in the cilia of olfactory sensory neurons of the nose. Each olfactory neuron expresses one single type of odorant receptor, and neurons expressing the same type of receptor project their axons to one or a few glomeruli in the olfactory bulb, creating a map of odorant receptor inputs. The information is then passed on to other regions of the brain, leading to odorant perception. To understand how the olfactory system discriminates between odorants, it is necessary to determine the odorant specificities of individual odorant receptors. These studies are complicated by the extremely large size of the odorant receptor family and by the poor functional expression of these receptors in heterologous cells. This article provides an overview of the methods that are currently being used to investigate odorant receptor–ligand interactions.     

Olfaction spontaneously highlights visual saliency map

Attention is intrinsic to our perceptual representations of sensory inputs. Best characterized in the visual domain, it is typically depicted as a spotlight moving over a saliency map that topographically encodes strengths of visual features and feedback modulations over the visual scene. By introducing smells to two well-established attentional paradigms, the dot-probe and the visual-search paradigms, we find that a smell reflexively directs attention to the congruent visual image and facilitates visual search of that image without the mediation of visual imagery. Furthermore, such effect is independent of, and can override, top-down bias. We thus propose that smell quality acts as an object feature whose presence enhances the perceptual saliency of that object, thereby guiding the spotlight of visual attention. Our discoveries provide robust empirical evidence for a multimodal saliency map that weighs not only visual but also olfactory inputs.     

Verbal cues modulate hedonic perception of odors in 5-year-old children as well as in adults

The judgment of pleasantness/unpleasantness is the prominent reaction to the olfactory world. In human adults, the hedonic valence of odor perception is affected by various factors, among which is an individual's lexical knowledge about smells. The present study examined whether such top-down effects of lexical knowledge on hedonic judgment of olfactory input are similar in children (5-6 years) and adults (20-25 years). In both groups, the lexical knowledge was found to influence the perception of the least emotional (or most neutral) odors: the pleasantness of the smells of banana and mint was enhanced when participants were given the corresponding odor label before olfactory sensation. These results lend support to the notion that, during childhood, smells are not only encoded perceptually but that verbal encoding also steers contextual effects that may be prominent factors in the early memorization and categorization of odors.