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Odor Sensor (Under Construction)
Development of Odor Sensor

In the atmosphere, various volatiles are contained. Some play important effects on our health, for example, volatiles generated by plants and woods make us comfortable, which are also used as an aromatic therapy. However, some other volatiles are known to lead to a health hazard, for example, chemical substances contained in house-paint, cigarettes and so on. These substances make serious effect to human body sometimes instantly with even a low concentration. For protecting human health from those serious substances we need to detect them correctly and instantly even in low concentration contained in the air. Odor detection is also important and useful for a rescue operation to find out buried people in disaster area, for conducting a drug at an airport, for finding out explosive substance including mine, and so on. For those serious social problems, highly sensitive and selective odor sensors are necessary and expected to be developed as soon as possible.

Existing odorant sensors are mainly fabricated based on metal-oxide semiconductor devices or quartz crystal microbalances. These sensors have been used for practical odorant-detection applications, because of their long-term stability and physicochemical principles. However, the performance of these sensors is still inferior to that of olfactory systems of living organisms in terms of selectivity, sensitivity, and response time. Moreover, for detecting chemical substances gas chromatography and mass spectrometer have been used as conventional approaches, which can detect a ppb level concentration of substances. However, it is difficult to detect substances with a real time resolution. It is also a problem that these equipments are very expensive and needs an expert for operation. As other chemical sensors antigen-antibody reaction has been developed and some of which are in practical use. However, there are some problems to solve, for example, sensitivity, selectivity, response time, cost, and so on. So we must develop advanced chemical sensors by solving those problems because the chemical sensors should be widely used for our safe and secure lives.

To solve those problems chemical sensors based on biological systems are noteworthy. Some chemical sensors using biological systems have been reported such as yeast cells (Radhika et al., 2007), neurons (Figueroa et al., 2010), frog eggs (Misawa et al., 2009), and culture cells.

Odor sensors using yeast cells are developed by using receptive mechanisms of pheromone called mating factor in Saccharomyces cerevisiae (Radhika et al., 2007、Minic et al., 2004、Pajot-Augy et al., 2003). So far yeast cells have been used as protein expressing system for examining a function of proteins. For example, this system has been applied to reveal the function of receptors of neurotransmitters in mammals. Some mammalian olfactory receptor proteins (i.e.,G-protein coupled receptors; GPCRs) are expressed in this yeast system. Responses of these GPCRs expressed in the yeasts were measured by surface plasmon resonance (SPR) (Minic et al., 2006). However, it is not easy to express GPCRs in the yeast cells or other organisms because of its complex system. The yeast cell is not enough for a target system of odor sensors, where a variety of odorant receptor proteins is expressed. So Figueroa et al. have developed odor sensors using olfactory receptor neurons (ORNs) of mice as olfactory sensors (Figueroa et al., 2010). They isolated about 20,000 ORNs from a mouse which were placed in a well of a micro-fluid. Olfactory responses of these ORNs were recorded by using a Ca-imaging technique. It was reported that they succeeded in discriminating four different odors by analyzing the spatio-temporal patterns of these ORNs.

On the other hand, Living organisms, especially insects, are equipped with sophisticated molecular mechanisms, starting with odorant receptors, which enable sensitive real-time detection of various types of odorants present in the environment. Although insect olfactory receptors selectively respond to a variety of odorants, transduction mechanisms are different from those of mammals. Insects use ionotropic channels for detecting odorants. This system is much easily reconstructed on the cell membrane using genetic engineering. Misawa et al. (2009) succeeded in expressing silkmoth olfactory receptors (i.e., pheromone receptors) on a frog egg membrane. They developed an olfactory sensor by fusing bioengineering and MEMS (Micro Electro Mechanical systems) technology applied to Xenopus egg cells. Using this system it was clarified that insect receptors work well as olfactory sensors. Different odors will be discriminated with high-sensitivity and high-temporal resolution by developing a micro-fluid equipment where eggs expressing different odorant receptors are arranged. However, the life-time of the egg is limited within just a few hours.

Recently, advanced odor sensors have been reported by Kanzaki’s group of the University of Tokyo. Focusing on the olfactory mechanisms of insects, they have developed two odorant sensor elements based on culture cell lines and transgenic silkmoths, that is, insect odorant receptor genes are inserted into their genome with genetic engineering techniques. One sensor element using insect cultured cell lines, Sf21 cell line, is able to sensitively detect odorants by increasing their fluorescent intensities over at least 2 months. The other sensor element using transgenic silkmoths, Bombyx mori, has not only sensitive odorant detection but also odor source orientation. These results show that their proposed sensor elements can be applied to detect various kinds of odorants with high sensitivity and selectivity, and provide an innovative platform to develop odorant sensors with high performance.

In addition to the odor sensors using biological materials described above, new technology has been developed where olfactory receptor proteins are expressed on artificially generated lipid bilayers (membrane).

In near future bioengineering using insect olfactory receptors will break the new direction of olfactory sensor.



    

匂い源探知ロボット:ガス漏れ探知、火災源の早期発見、有害物質や環境汚染物質の発生源の探知、被災地での匂いを手掛かりとした救助活動、さらには空港での麻薬などの検査、爆発物や地雷の検知など


References

Figueroa X.A., Cooksey G.A., Votaw S.V., Horowitz L.F. & Folch A. (2010) Large-scale investigation of the olfactory receptor space using a microfluidic microwell array. Lab Chip DOI: 10.1039/b920585c.

Kiely A., Authier A., Kralicek A.V., Warr C.G. & Newcomb R.D. (2007) Functional analysis of a Drosophila melanogaster olfactory receptor expressed in Sf9 cells. J. Neutosci. Methods 159, 189-194.

Misawa N., Mitsuno H., Kanzaki R. & Takeuchi S. (2009) Microfluidic odorant sensor with frog eggs expressing olfactory receptors. 22nd IEEE International Conference on Micro Electro Mechanical Systems pp.180-183.

Minic J., Persuy M.A., Godel E., Aioun J., Connerton I., Salesse R. & Pajot-Augy E. (2005) Functional expression of olfactory receptors in yeast and development of a bioassay for odorant screening. FEBS J. 272, 524-537.

Minic J., Grosclaude J., Persuy M.A., Aioun J., Salesse R. & Pajot-Augy E. (2006) Quantitative assessment of olfactory receptors activation in immobilized nanosomes: a novel concept for bioelectronic nose. Lab Chip 6, 1026-1032.

Neuhaus E.M., Gisselmann G., Zhang W., Dooley R., Stortkuhl K. & Hatt H. (2005) Odorant receptor heterodimerization in the olfactory system of Drosophila melanogaster. Nat. Neurosci. 8, 15-17.

Pajot-Augy E., Crowe M., Levasseur G., Salesse R. & Connerton I. (2003) Engineered yeasts as reporter systems for odorant detection. J. Recept. Signal Transduct. Res. 23, 155-171.

Radhika V., Proikas-Cezanne T., Jayaraman M., Onesime D., Ha J.H. & Dhanasekaran D.N. (2007) Chemical sensing of DNT by engineered olfactory yeast strain. Nat. Chem. Biol. 3, 325-330

Sato K., Pellegrino M., Nakagawa T., Nakagawa T., Vosshall L.B. & Touhara K. (2008) Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature 452, 1002-1006.

Wicher D., Schafer R., Bauernfeind R., Stensmyr M.C., Heller R., Heinemann S.H. & Hansson B.S. (2008) Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature 452, 1007-1011.


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