Concept of Bioelectronic Nose - Bioelectronic Nose: Integration of Biotechnology and Nanotechnology - page 16

numerous odorants can affect ORs. Thus, incalculable combinations between ORs
and odorants exist, and the relationship should be investigated further [ 97 ]. Follow-
ing the further investigation of the specific function of ORs, the application area of
bioelectronic noses will continue to grow.
Another current issue is the detection of gaseous odorants. In actual olfaction,
the binding event between ORs and odorants occurs in the nasal mucus, an aqueous
solution [ 27 ]. Although most odorants are hydrophobic and well-vaporized, odor-
ants can dissolve well in mucus due to OBPs naturally existing in mucus [ 98 , 99 ].
Thus, studies on OBPs are currently being conducted. Also, if ORs are active in dry
conditions, the problem can be easily solved. Since most proteins are functional
in aqueous solutions, it is challenging to make active ORs in dry conditions using
nanodiscs or amphipols [ 100 ].
The most interesting thing in bioelectronic noses is that OR-based sensors can
mimic the olfactory system. Types of odors have not yet been fundamentally and
scientifically classified. Thus, there is no other choice but to recognize specific
odors based on personal experience. However, bioelectronic noses will offer a way
to classify odors. Each odor has a unique response pattern with activated ORs [ 28 ,
97 ]. A sensor functionalized with a multi-array of all types of ORs can represent
whole response patterns in vitro . This means that bioelectronic noses can classify
the types of odor without the help of the human nose. Thus, multi-array sensor plat-
forms are being developed to fundamentally understand the characteristics of odors.
Other G protein-coupled receptors (GPCRs) such as taste receptors and hormone
receptors can be utilized for the development of biosensor systems through the
same strategy as that of the bioelectronic noses [ 89 - 92 ]. Most GPCRs, regardless
of their GPCR classes, can be produced in mammalian cells or E. coli, similar to
the expression of ORs. The hybridization between receptors and secondary trans-
ducers has facilitated the development of highly sensitive and selective biosensor
systems. A bioelectronic tongue fabricated with human bitter taste receptors and
FETs was able to selectively detect bitter compounds at concentrations as low as
1 fM [ 90 , 92 ]. Moreover, target tastants were efficiently detected in a mixture and
a real food sample [ 92 ]. Human parathyroid hormone receptors (hPTHRs) were
also expressed in E. coli and used for the functionalization of conducting polymer
nanoparticle-based FETs [ 91 ]. hPTHR is a class B GPCR, while OR is a class A
GPCR [ 101 ]. Even though class B GPCRs have larger size and more complicated
structure compared to class A GPCRs, functional hPTHRs were successfully over-
expressed in E. coli . The biosensor based on hPTHRs sensitively and selectively
detected hPTHs, as shown in Fig. 1.7 . In this case, the secondary sensing material
was conducting polymer nanoparticles, and the particle size had been modulated to
improve the sensitivity. The small nanoparticles (20-nm diameter) detected hPTH
more sensitively than the larger nanoparticles (60 or 100-nm diameter) (Figs. 1.7a
and b ). Moreover, the sensor had excellent selectivity capable of discriminating
hPTH among other hormones, such as GLP-1, glucagon, and secretin (Figs. 1.7c
and d ). All these results indicate that the devices functionalized with GPCRs will
allow us to develop not only bioelectronic noses and tongues, but also other biosen-
sors for disease diagnosis.