Bioelectronic nose and its application to smell...
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REVIEW Open Access
Bioelectronic nose and its application tosmell visualizationHwi Jin Ko1 and Tai Hyun Park1,2,3*
There have been many trials to visualize smell using various techniques in order to objectively express the smellbecause information obtained from the sense of smell in human is very subjective. So far, well-trained experts suchas a perfumer, complex and large-scale equipment such as GC-MS, and an electronic nose have played major rolesin objectively detecting and recognizing odors. Recently, an optoelectronic nose was developed to achieve thispurpose, but some limitations regarding the sensitivity and the number of smells that can be visualized still persist.Since the elucidation of the olfactory mechanism, numerous researches have been accomplished for the developmentof a sensing device by mimicking human olfactory system. Engineered olfactory cells were constructed to mimic thehuman olfactory system, and the use of engineered olfactory cells for smell visualization has been attempted with theuse of various methods such as calcium imaging, CRE reporter assay, BRET, and membrane potential assay; however, itis not easy to consistently control the condition of cells and it is impossible to detect low odorant concentration.Recently, the bioelectronic nose was developed, and much improved along with the improvement of nano-biotechnology. The bioelectronic nose consists of the following two parts: primary transducer and secondarytransducer. Biological materials as a primary transducer improved the selectivity of the sensor, and nanomaterialsas a secondary transducer increased the sensitivity. Especially, the bioelectronic noses using various nanomaterialscombined with human olfactory receptors or nanovesicles derived from engineered olfactory cells have a potentialwhich can detect almost all of the smells recognized by human because an engineered olfactory cell might be able toexpress any human olfactory receptor as well as can mimic human olfactory system. Therefore, bioelectronic nose willbe a potent tool for smell visualization, but only if two technologies are completed. First, a multi-channel array-sensingsystem has to be applied for the integration of all of the olfactory receptors into a single chip for mimicking theperformance of human nose. Second, the processing technique of the multi-channel system signals should besimultaneously established with the conversion of the signals to visual images. With the use of this latest sensingtechnology, the realization of a proper smell-visualization technology is expected in the near future.
Keywords: Olfactory receptor, Odorant, Engineered olfactory cells, Nanovesicles, Bioelectronic nose, Optoelectronicnose, Nano-biotechnology, Smell visualization
BackgroundThe sense of smell plays an important role in human life.Through smelling, the freshness, quality, and taste offood can be assessed, and dangerous materials and situa-tions can be evaluated; moreover, pleasant odors such asa fragrance of flower, perfume, and air freshener can beused for refreshment, and sometimes memories can berecalled. Nevertheless, the exact information of smells
cannot be precisely articulated, as the expression ofsmell is subjective, and the same smell can be recog-nized differently by different people because smell recog-nition also depends on personal experience and smellingability.More than 100 years ago, scientists tried to describe
and classify odors [3, 7, 11, 16, 51, 63], but it proved tobe impossible. Recently, various attempts were made todisplay the smells from a device that was transmittingflavors over the Internet to engineered olfactory cellsand optoelectronic noses using metalloporphyrins [31,44, 68, 69]. But still, it is not easy to visualize smells
* Correspondence: [email protected] Institute, Seoul 151-742, Republic of Korea2School of Chemical and Biological Engineering, Seoul National University,Seoul 151-742, Republic of KoreaFull list of author information is available at the end of the article
The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Ko and Park Journal of Biological Engineering (2016) 10:17 DOI 10.1186/s13036-016-0041-4
because there are several limitations, such as a limitednumber of smells for visualization, a low sensitivity, a lowreproducibility, and a complex process, to overcome.The bioelectronic nose will be a possible solution for
the smell-visualization problem. The successful cloningand expression of the human olfactory receptors  forthe development of the bioelectronic nose and the devel-opment of nano-biotechnology have improved the per-formance of the bioelectronic nose. The bioelectronicnose is constructed with biological materials that havebeen integrated with nanomaterials such as carbonnanotube, conducting polymer, and graphene [21, 27, 42,67]. The use of the olfactory receptor as a biological ma-terial greatly improved the selectivity of the sensor sothat the bioelectronic nose discriminates the differencebetween single carbon atoms , and several nanoma-terials extremely enhanced the sensitivity so that thesensor could detect an odorant at a concentration of0.02 ppt .The sense of smell is importantly used for the daily
lives of humans including determination of food fresh-ness, the recalling of memories, and the perception ofdangerous materials or dangerous situations like fires;unfortunately, though, anosmia and hyposmia patientscannot be provided with any technological benefits atthe present time; therefore, smell visualization is neededfor this purpose and it can be achieved by transferringsmell information to the general public including peoplewith olfactory problem, who are not experts, by convert-ing the complex electrical signals of bioelectronic noseto any simple visualized form, so that they easily can getor see the smell information without analysis of complexsignals. By using olfactory receptors, the bioelectronicnose can also detect a huge variety of smells like the hu-man nose. Thus, it is expected that these properties ofthe bioelectronic nose will play an important role insmell visualization for many applications, and this reviewfeatures the potential of the bioelectronic nose as a use-ful tool for the visualization of smells.
Human olfactionThe human olfactory system is a sensory system for thesmelling of odor molecules and is composed of the areafrom the olfactory epithelium to the olfactory cortex. Humans can smell and recognize a variety of odor-ants that are processed by the sense of smell, and thisfunction is known as an olfaction. Odorants reach themucus-covered olfactory epithelium in the nasal cavityand then bind to the olfactory receptors, which exist inthe cilial membrane of the olfactory sensory neurons,and then the odorant information is transferred fromthe olfactory sensory neurons to the brain. Ion channelsare also located in the mucus-covered cilial membranesand play a role in activation of olfactory neurons. Mucus
contains odorant-binding proteins that play a major rolein the transportation of odor molecules to the olfactoryreceptor proteins in the aqueous mucus that is facilitatedby the solubilization of hydrophobic odor molecules [12,43]. The binding of odorants to the olfactory receptorsinduces a conformational change of the olfactory recep-tor proteins, resulting in a signal transduction throughthe cAMP pathway or the IP3 pathway that is followedby the activation of olfactory neurons by the transporta-tion of ions [6, 18, 47]. The number of the functional ol-factory receptors of human is approximately 400, andhumans can recognize approximately 10,000 odorantsthrough the combination of these olfactory receptors. The olfactory receptor is the initial part that dis-criminates and recognizes the odorants in olfaction.Many researchers have tried to utilize the olfactory re-ceptors that are heterologously expressed in various cellsfor the development of artificial olfactory sensors, as wellas for studies on olfaction, and these efforts are becom-ing fruitful in this research field.
Artificial olfactory systemEngineered olfactory cellSince the 1990s, many research groups have been tryingto figure out olfactory signaling and the deorphanizationof olfactory receptors by using the olfactory epitheliumtissues that are derived from animals, or by using theanimal itself, including a rat , frog , C. elegance, and zebra fish . Several limitations, such as dif-ficulties regarding the maintenance of fresh tissues, theattainment of a continuous supply of the same experi-mental materials from the animals, the analysis of theresponses from unidentified olfactory receptors, and thedetection and analysis of the signals that are derivedfrom the animals, arose for this kind of approach. Toovercome these limitations, engineered olfactory cellswere constructed through the heterologous expressionof the olfactory receptors in mammalian cells [23, 25],insect cells , Xenopus oocyte , and yeasts .Especially, the engineered olfactory cells using mamma-lian cells have been used as a useful tool for deor