Protein- and Peptide-Based Biosensors in Artificial Olfaction
2018; Elsevier BV; Volume: 36; Issue: 12 Linguagem: Inglês
10.1016/j.tibtech.2018.07.004
ISSN0167-9430
AutoresArménio Jorge Moura Barbosa, Ana Rita Oliveira, Ana Cecília A. Roque,
Tópico(s)Biochemical Analysis and Sensing Techniques
ResumoArtificial olfaction is being implemented in key societal areas like early disease diagnostics, food safety hazards, air quality, and security. Protein- and peptide-based VOC biosensors, coupled with cutting-edge transducers, increase the selectivity and sensitivity in detecting key VOCs with limits of detection in the order of ppb. Gas-phase testing, rather than VOC solutions, is becoming the state of the art in biosensor validation. Combinatorial techniques such as phage display and virtual screening are advancing the discovery of new VOC-binding peptides. Progresses in biomolecule immobilization are steadily increasing the reusability and shelf-life of biosensors, while maintaining the desired selectivity. Animals' olfactory systems rely on proteins, olfactory receptors (ORs) and odorant-binding proteins (OBPs), as their native sensing units to detect odours. Recent advances demonstrate that these proteins can also be employed as molecular recognition units in gas-phase biosensors. In addition, the interactions between odorant molecules and ORs or OBPs are a source of inspiration for designing peptides with tunable odorant selectivity. We review recent progress in gas biosensors employing biological units (ORs, OBPs, and peptides) in light of future developments in artificial olfaction, emphasizing examples where biological components have been employed to detect gas-phase analytes. Animals' olfactory systems rely on proteins, olfactory receptors (ORs) and odorant-binding proteins (OBPs), as their native sensing units to detect odours. Recent advances demonstrate that these proteins can also be employed as molecular recognition units in gas-phase biosensors. In addition, the interactions between odorant molecules and ORs or OBPs are a source of inspiration for designing peptides with tunable odorant selectivity. We review recent progress in gas biosensors employing biological units (ORs, OBPs, and peptides) in light of future developments in artificial olfaction, emphasizing examples where biological components have been employed to detect gas-phase analytes. The possibility of mimicking nature, building artificial intelligent systems to perform complex tasks, and dealing with large sets of data is gaining increasing relevance in all areas, including biological sciences [1Castelvecchi D. Can we open the black box of AI?.Nature. 2016; 538: 20-23Crossref PubMed Scopus (610) Google Scholar]. The mysteries of olfaction, in particular human olfaction, still intrigue scientists and, not surprisingly, it is considered the least understood sense [2Wang P. et al.Bioinspired Smell and Taste Sensors. Springer, 2015Crossref Scopus (2) Google Scholar, 3McGann J.P. Poor human olfaction is a 19th-century myth.Science. 2017; 356eaam7263Crossref PubMed Scopus (238) Google Scholar]. Artificial olfaction systems aim to mimic the sense of smell and typically consist of electronic nose devices (e-noses) (see Glossary) that include an array of gas sensors associated with signal-processing tools [4Fitzgerald J.E. et al.Artificial nose technology: status and prospects in diagnostics.Trends Biotechnol. 2017; 35: 33-42Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 5Zhang X. et al.An overview of an artificial nose system.Talanta. 2018; 184: 93-102Crossref PubMed Scopus (30) Google Scholar, 6Persaud K.C. Towards bionic noses.Sens. Rev. 2017; 37: 165-171Crossref Scopus (8) Google Scholar]. Classically, in an e-nose, a sample enters the system through an inlet that guides the gas molecules to a chamber where the sensing material is deposited. The interaction of the volatile organic compounds (VOCs) with the sensing material generates a signal (for example, electric, optical, or gravimetric) that is transduced and further processed by a signal-processing computer. Odors are typically composed of a set of VOCs. The detection of VOCs is of significant interest, not only to understand biological processes, but also in several scientific and technological areas. For instance, VOC sensors hold great promise in the early diagnosis of diseases [7Broza Y.Y. et al.Hybrid volatolomics and disease detection.Angew. Chem. Int. Ed. Engl. 2015; 54: 11036-11048Crossref PubMed Scopus (175) Google Scholar, 8Krilaviciute A. et al.Detection of cancer through exhaled breath: a systematic review.Oncotarget. 2015; 6: 38643-38657Crossref PubMed Scopus (118) Google Scholar, 9Vishinkin R. Haick H. Nanoscale sensor technologies for disease detection via volatolomics.Small. 2015; 11: 6142-6164Crossref PubMed Scopus (139) Google Scholar, 10Fitzgerald J. Fenniri H. Cutting edge methods for non-invasive disease diagnosis using e-tongue and e-nose devices.Biosensors. 2017; 7: 59Crossref Scopus (27) Google Scholar, 11Cruz H. et al.Development of e-nose biosensors based on organic semiconductors towards low-cost health care diagnosis in gynecological diseases.Mater. Today Proc. 2017; 4: 11544-11553Crossref Scopus (2) Google Scholar, 12Rocco G. Every breath you take: the value of the electronic nose (e-nose) technology in the early detection of lung cancer.J. Thorac. Cardiovasc. Surg. 2018; 155: 2622-2625Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar], food quality control [13Srivastava A.K. et al.Nanosensors and nanobiosensors in food and agriculture.Environ. Chem. Lett. 2018; 16: 161-182Crossref Scopus (121) Google Scholar, 14Loutfi A. et al.Electronic noses for food quality: a review.J. Food Eng. 2015; 144: 103-111Crossref Scopus (527) Google Scholar, 15Zanardi E. et al.New insights to detect irradiated food: an overview.Food Anal. Methods. 2018; 11: 224-235Crossref Scopus (23) Google Scholar], security [16Giannoukos S. et al.Chemical sniffing instrumentation for security applications.Chem. Rev. 2016; 116: 8146-8172Crossref PubMed Scopus (126) Google Scholar], agriculture [17Cui S. et al.Plant pest detection using an artificial nose system: a review.Sensors. 2018; 18: 378Crossref Scopus (98) Google Scholar], environmental monitoring [18Szulczyński B. et al.Different ways to apply a measurement instrument of e-nose type to evaluate ambient air quality with respect to odour nuisance in a vicinity of municipal processing plants.Sensors (Switzerland). 2017; 17: E2671Crossref PubMed Scopus (46) Google Scholar], and insect supervision [19Dung T. et al.Applications and advances in bioelectronic noses for odour sensing.Sensors. 2018; 18: 103Crossref Scopus (57) Google Scholar, 20Wasilewski T. et al.Bioelectronic nose: current status and perspectives.Biosens. Bioelectron. 2017; 87: 480-494Crossref PubMed Scopus (98) Google Scholar]. The broad range of application areas for e-noses has been accelerating the progress of gas-sensing technologies, with an extensive research and market space for developing new sensing materials and devices [2Wang P. et al.Bioinspired Smell and Taste Sensors. Springer, 2015Crossref Scopus (2) Google Scholar]. Current gas-sensing materials, including those commercially available, include mostly metal oxide semiconductors and conductive polymers. The main drawbacks of these systems are the low stability and high promiscuity towards VOC molecules, resulting in low selectivity. As such, incorporating the sensing components of biological olfaction systems into gas-sensing materials can increase the VOC selectivity of the resultant gas sensors and bio-electronic noses (Figure 1) [4Fitzgerald J.E. et al.Artificial nose technology: status and prospects in diagnostics.Trends Biotechnol. 2017; 35: 33-42Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 6Persaud K.C. Towards bionic noses.Sens. Rev. 2017; 37: 165-171Crossref Scopus (8) Google Scholar, 19Dung T. et al.Applications and advances in bioelectronic noses for odour sensing.Sensors. 2018; 18: 103Crossref Scopus (57) Google Scholar, 20Wasilewski T. et al.Bioelectronic nose: current status and perspectives.Biosens. Bioelectron. 2017; 87: 480-494Crossref PubMed Scopus (98) Google Scholar, 21Wasilewski T. et al.Advances in olfaction-inspired biomaterials applied to bioelectronic noses.Sens. Actuators B Chem. 2018; 257: 511-537Crossref Scopus (50) Google Scholar, 22Son M. et al.Bioelectronic nose: an emerging tool for odor standardization.Trends Biotechnol. 2017; 35: 301-307Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar]. Still, most published works report biosensing using VOC analytes in solutions [23Sanmartí-espinal M. et al.Quantification of interacting cognate odorants with olfactory receptors in nanovesicles.Sci. Rep. 2017; 7: 1-11Crossref PubMed Scopus (8) Google Scholar, 24Mitsuno H. et al.Novel cell-based odorant sensor elements based on insect odorant receptors.Biosens. Bioelectron. 2015; 65: 287-294Crossref PubMed Scopus (64) Google Scholar, 25Mulla M.Y. et al.Capacitance-modulated transistor detects odorant binding protein chiral interactions.Nat. Commun. 2015; 6: 1-9Crossref Scopus (179) Google Scholar, 26Kotlowski C. et al.Fine discrimination of volatile compounds by graphene-immobilized odorant-binding proteins.Sens. Actuators B Chem. 2018; 256: 564-572Crossref Scopus (36) Google Scholar, 27Larisika M. et al.Electronic olfactory sensor based on A. mellifera odorant-binding protein 14 on a reduced graphene oxide field-effect transistor.Angew. Chem. Int. Ed. Engl. 2015; 54: 13245-13248Crossref PubMed Scopus (66) Google Scholar], in contrast to the real-life implementation of e-noses to analyse gaseous samples. Therefore, this review focuses only on recent research trends in gas-phase biosensing. Olfactory receptors (ORs) are believed to recognize different odorants, so odorant recognition depends on the OR being activated and on the extent of its activation [28Antunes G. Simoes de Souza F.M. Olfactory receptor signaling.Methods Cell Biol. 2016; 132: 127-145Crossref PubMed Scopus (28) Google Scholar, 29Behrens M. et al.Structure–function relationships of olfactory and taste receptors.Chem. Senses. 2018; 43: 81-87Crossref PubMed Scopus (33) Google Scholar] (Box 1). Identifying which odorants specifically bind to a certain OR is called deorphanization [30de Fouchier A. et al.Functional evolution of Lepidoptera olfactory receptors revealed by deorphanization of a moth repertoire.Nat. Commun. 2017; 815709Crossref PubMed Scopus (97) Google Scholar, 31Silva Teixeira C.S. et al.Unravelling the olfactory sense: from the gene to odor perception.Chem. Senses. 2016; 41: 105-121PubMed Google Scholar]. The deorphanization of ORs is a crucial step to understand several aspects of the smelling sensory process, including the complete knowledge of an OR's activity, the impact of the physicochemical properties of odorant molecules in an OR's selectivity, and the way in which information is accurately processed to generate the recognized pattern that culminates in the final olfactory perception [31Silva Teixeira C.S. et al.Unravelling the olfactory sense: from the gene to odor perception.Chem. Senses. 2016; 41: 105-121PubMed Google Scholar]. These studies must take into account the ability of an odorant to be recognized by multiple ORs, and the fact that a specific OR can recognize several odorants. Some ORs have already been isolated and applied to gas-sensing biosensors (Table 1).Box 1Differences between Proteins and Peptides Currently Used in VOC BiosensingThe biomolecules applied so far in gas biosensing include ORs, OBPs, and peptides, with remarkable structural differences highlighted in Figure I.ORs are members of the G protein-coupled receptor family: they are structurally defined by seven trans-membrane α-helices, about 320 amino acid residues in length [29Behrens M. et al.Structure–function relationships of olfactory and taste receptors.Chem. Senses. 2018; 43: 81-87Crossref PubMed Scopus (33) Google Scholar]. These proteins, upon volatile binding, generate a signal that is transmitted from the olfactory sensory neurons, where ORs are located, to the brain in a recognized pattern that culminates in olfactory perception.Mammalian OBPs belong to the lipocalin superfamily of proteins, transport proteins [38Persaud K.C. Tuccori E. Biosensors based on odorant binding proteins.in: Park T.H. Bioelectronic Nose. Springer, 2014: 171-190Crossref Scopus (7) Google Scholar, 41Northey T. et al.Crystal structures and binding dynamics of odorant-binding protein 3 from two aphid species Megoura viciae and Nasonovia ribisnigri.Sci. Rep. 2016; 624739Crossref PubMed Scopus (44) Google Scholar, 42Pelosi P. et al.Structure and biotechnological applications of odorant-binding proteins.Appl. Microbiol. Biotechnol. 2014; 98: 61-70Crossref PubMed Scopus (117) Google Scholar] that are 150–160 residues in length [43Mastrogiacomo R. et al.An odorant-binding protein is abundantly expressed in the nose and in the seminal fluid of the rabbit.PLoS One. 2014; 9: 45-48Crossref Scopus (25) Google Scholar] and have typical lipocalin-fold of eight anti-parallel β-sheets and a short α-helix close to the C terminal. The β-sheets form an antiparallel β-barrel shaping a central pocket for ligand binding [44Schiefner A. et al.Crystal structure of the human odorant binding protein, OBP IIa.Proteins. 2015; 83: 1180-1184Crossref PubMed Scopus (19) Google Scholar]. Insect OBPs present well-conserved folding with protein chains of 130–150 amino acids [40Brito N.F. et al.A look inside odorant-binding proteins in insect chemoreception.J. Insect Physiol. 2016; 95: 51-65Crossref PubMed Scopus (175) Google Scholar]. The tertiary protein structure comprises a compact set of six α-helices with a hydrophobic cavity. Additionally, the folding is stabilized by the presence of three disulfide bonds [39Pelosi P. et al.Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects.Biol. Rev. 2018; 93: 184-200Crossref PubMed Scopus (292) Google Scholar, 40Brito N.F. et al.A look inside odorant-binding proteins in insect chemoreception.J. Insect Physiol. 2016; 95: 51-65Crossref PubMed Scopus (175) Google Scholar]. These disulfide bonds are considered the fingerprint of insect OBPs. Notwithstanding amino acid variability, the overall structure of insect OBPs is highly conserved, even among members of different orders of insects [39Pelosi P. et al.Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects.Biol. Rev. 2018; 93: 184-200Crossref PubMed Scopus (292) Google Scholar, 40Brito N.F. et al.A look inside odorant-binding proteins in insect chemoreception.J. Insect Physiol. 2016; 95: 51-65Crossref PubMed Scopus (175) Google Scholar, 78Carraher C. et al.Towards an understanding of the structural basis for insect olfaction by odorant receptors.Insect Biochem. Mol. Biol. 2015; 66: 31-41Crossref PubMed Scopus (61) Google Scholar].Peptides represent a simple and low-cost option for biosensors. Ranging from approximately 5 to 15 protein residues, they can be synthetically or biologically produced. Their selectivity towards target VOCs is easier to tune due to their small size [20Wasilewski T. et al.Bioelectronic nose: current status and perspectives.Biosens. Bioelectron. 2017; 87: 480-494Crossref PubMed Scopus (98) Google Scholar, 56Sankaran S. et al.Biology and applications of olfactory sensing system: a review.Sens. Actuators B Chem. 2012; 171–172: 1-17Crossref Scopus (105) Google Scholar]. VOC-sensing peptides have been developed by different approaches (Box 2, Figure 2), and applied in several substrates and sensing devices, as summarized in Table 2.Table 1Protein Biosensors in Gas SensingProteinVOCsSupportTransducerLoD/measuredaIndicates when the detected concentration was not the LoD, but the "measured" in that paper.SourceExpression systemRefsOlfactory receptorsOR-10DiacetylGoldQCM1 × 10−12 MC. elegansE. coli32Sung J.H. et al.Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli.Biosens. Bioelectron. 2006; 21: 1981-1986Crossref PubMed Scopus (98) Google ScholarSAW1.2 × 10−11 mMMCF-7 cells34Wu C. et al.A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors.Biosens. Bioelectron. 2012; 31: 44-48Crossref PubMed Scopus (29) Google ScholarhOR 17–40hOR3A1HelionalCNTInterdigitated microelectrode array,Current-voltage0.02 pptHomo sapiensMC18 (Saccharomyces cerevisiae)HEK-293T cells36Lee S.H. et al.Mimicking the human smell sensing mechanism with an artificial nose platform.Biomaterials. 2012; 33: 1722-1729Crossref PubMed Scopus (96) Google ScholarmOR174-9mOR203-1mOR256-17Acetophenone, OthersCNTCNT transistors, Current-gate Voltage1–10 μMMus musculusS. cerevisiae35Goldsmith B.R. et al.Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins.ACS Nano. 2011; 5: 5408-5416Crossref PubMed Scopus (141) Google ScholarOdorant-binding proteinsAaegOBP22N,N-diethyl-meta-toluamide (DEET)GoldZnO film bulk acoustic resonators–A. aegyptiE. coli55Zhao X. et al.Protein functionalized ZnO thin film bulk acoustic resonator as an odorant biosensor.Sens. Actuators B Chem. 2012; 163: 242-246Crossref Scopus (35) Google ScholarpOBPEthanol; methanolSiSi-substrate with interdigitated electrodes (EIS)20 ppmaIndicates when the detected concentration was not the LoD, but the "measured" in that paper.; 10 ppmaIndicates when the detected concentration was not the LoD, but the "measured" in that paper.Sus scrofaPig nasal tissue46Capone S. et al.Electrical characterization of a pig odorant binding protein by impedance spectroscopy.Proc. IEEE Sens. 2009; 2009: 1758-1762Google ScholarpOBP(R)-(−)-1-octen-3-ol (octenol); (R)-(−)-carvone (carvone)GoldSAW0.48 ppm; 0.72 ppmS. scrofaPig nasal tissue47Di Pietrantonio F. et al.Surface acoustic wave biosensor based on odorant binding proteins deposited by laser induced forward transfer.IEEE Int. Ultrason. Symp. 2013; 2013: 2144-2147Google ScholarwtbOBP(R)-(−)-1-octen-3-ol (octenol); (R)-(−)-carvone (carvone)SAW0.2–0.23 ppm (carvone); 0.18–0.21 ppm (octenol)Bos taurusBL21-DE3 E. Coli49Di Pietrantonio F. et al.Tailoring odorant-binding protein coatings characteristics for surface acoustic wave biosensor development.Appl. Surf. Sci. 2014; 302: 250-255Crossref Scopus (16) Google ScholarpOBPwtbOBPdmbOBP(R)-(−)-1-octen-3-ol (octenol); (R)-(−)-carvone (carvone)GoldSAWwtpOBP: 25.9 (octenol), 7.0 (carvone) Hz/ppm;wtbOBP: 3.5 (octenol), 5.4 (carvone) Hz/ppm;dmbOBP: 6.0 (octenol), 9.2 (carvone) Hz/ppm;S. scrofa; B. TaurusPig nasal tissue; BL21-DE3 E. Coli51Di Pietrantonio F. et al.Detection of odorant molecules via surface acoustic wave biosensor array based on odorant-binding proteins.Biosens. Bioelectron. 2013; 41: 328-334Crossref PubMed Scopus (79) Google ScholarpOBP wtbOBP dmbOBP(R)-(−)-1-octen-3-ol (octenol); (R)-(−)-carvone (carvone)GoldSAW0.48 ppm (octenol); 0.74 ppm (carvone)S. scrofa; B. TaurusPig nasal tissue; E. coli52Di Pietrantonio F. et al.A surface acoustic wave bio-electronic nose for detection of volatile odorant molecules.Biosens. Bioelectron. 2015; 67: 516-523Crossref PubMed Scopus (45) Google ScholarwtbOBP(R)-(−)-1-octen-3-ol (octenol)GoldSolidly mounted resonator7 ppmB. taurusBL21-DE3 E. coli48Cannata D. et al.Odorant detection via solidly mounted resonator biosensor.IEEE Int. Ultrason. Symp. 2012; 2012: 1537-1540Google ScholarwtbOBP(R)-(−)-1-octen-3-ol (octenol); (R)-(−)-carvone (carvone)GoldSAW0.18 ppm; 0.2 ppmB. taurusBL21-DE3 E. Coli49Di Pietrantonio F. et al.Tailoring odorant-binding protein coatings characteristics for surface acoustic wave biosensor development.Appl. Surf. Sci. 2014; 302: 250-255Crossref Scopus (16) Google ScholarwtbOBP(R)-(−)-1-octen-3-ol (octenol)GoldSAW2 ppmB. taurusBL21-DE3 E. coli50Palla-Papavlu A. et al.Preparation of surface acoustic wave odor sensors by laser-induced forward transfer.Sens. Actuators B Chem. 2014; 192: 369-377Crossref Scopus (28) Google ScholarwtbOBP, dmbOBPDMMPSilicon nitratePhotonic ring resonator6.8 ppbB. taurusBL21-DE3 E. coli53Bonnot K. et al.Biophotonic ring resonator for ultrasensitive detection of DMMP as a simulant for organophosphorus agents.Anal. Chem. 2014; 86: 5125-5130Crossref PubMed Scopus (16) Google Scholara Indicates when the detected concentration was not the LoD, but the "measured" in that paper. Open table in a new tab The biomolecules applied so far in gas biosensing include ORs, OBPs, and peptides, with remarkable structural differences highlighted in Figure I. ORs are members of the G protein-coupled receptor family: they are structurally defined by seven trans-membrane α-helices, about 320 amino acid residues in length [29Behrens M. et al.Structure–function relationships of olfactory and taste receptors.Chem. Senses. 2018; 43: 81-87Crossref PubMed Scopus (33) Google Scholar]. These proteins, upon volatile binding, generate a signal that is transmitted from the olfactory sensory neurons, where ORs are located, to the brain in a recognized pattern that culminates in olfactory perception. Mammalian OBPs belong to the lipocalin superfamily of proteins, transport proteins [38Persaud K.C. Tuccori E. Biosensors based on odorant binding proteins.in: Park T.H. Bioelectronic Nose. Springer, 2014: 171-190Crossref Scopus (7) Google Scholar, 41Northey T. et al.Crystal structures and binding dynamics of odorant-binding protein 3 from two aphid species Megoura viciae and Nasonovia ribisnigri.Sci. Rep. 2016; 624739Crossref PubMed Scopus (44) Google Scholar, 42Pelosi P. et al.Structure and biotechnological applications of odorant-binding proteins.Appl. Microbiol. Biotechnol. 2014; 98: 61-70Crossref PubMed Scopus (117) Google Scholar] that are 150–160 residues in length [43Mastrogiacomo R. et al.An odorant-binding protein is abundantly expressed in the nose and in the seminal fluid of the rabbit.PLoS One. 2014; 9: 45-48Crossref Scopus (25) Google Scholar] and have typical lipocalin-fold of eight anti-parallel β-sheets and a short α-helix close to the C terminal. The β-sheets form an antiparallel β-barrel shaping a central pocket for ligand binding [44Schiefner A. et al.Crystal structure of the human odorant binding protein, OBP IIa.Proteins. 2015; 83: 1180-1184Crossref PubMed Scopus (19) Google Scholar]. Insect OBPs present well-conserved folding with protein chains of 130–150 amino acids [40Brito N.F. et al.A look inside odorant-binding proteins in insect chemoreception.J. Insect Physiol. 2016; 95: 51-65Crossref PubMed Scopus (175) Google Scholar]. The tertiary protein structure comprises a compact set of six α-helices with a hydrophobic cavity. Additionally, the folding is stabilized by the presence of three disulfide bonds [39Pelosi P. et al.Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects.Biol. Rev. 2018; 93: 184-200Crossref PubMed Scopus (292) Google Scholar, 40Brito N.F. et al.A look inside odorant-binding proteins in insect chemoreception.J. Insect Physiol. 2016; 95: 51-65Crossref PubMed Scopus (175) Google Scholar]. These disulfide bonds are considered the fingerprint of insect OBPs. Notwithstanding amino acid variability, the overall structure of insect OBPs is highly conserved, even among members of different orders of insects [39Pelosi P. et al.Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects.Biol. Rev. 2018; 93: 184-200Crossref PubMed Scopus (292) Google Scholar, 40Brito N.F. et al.A look inside odorant-binding proteins in insect chemoreception.J. Insect Physiol. 2016; 95: 51-65Crossref PubMed Scopus (175) Google Scholar, 78Carraher C. et al.Towards an understanding of the structural basis for insect olfaction by odorant receptors.Insect Biochem. Mol. Biol. 2015; 66: 31-41Crossref PubMed Scopus (61) Google Scholar]. Peptides represent a simple and low-cost option for biosensors. Ranging from approximately 5 to 15 protein residues, they can be synthetically or biologically produced. Their selectivity towards target VOCs is easier to tune due to their small size [20Wasilewski T. et al.Bioelectronic nose: current status and perspectives.Biosens. Bioelectron. 2017; 87: 480-494Crossref PubMed Scopus (98) Google Scholar, 56Sankaran S. et al.Biology and applications of olfactory sensing system: a review.Sens. Actuators B Chem. 2012; 171–172: 1-17Crossref Scopus (105) Google Scholar]. VOC-sensing peptides have been developed by different approaches (Box 2, Figure 2), and applied in several substrates and sensing devices, as summarized in Table 2. The first development of gas-phase biosensors for VOC detection used the receptor OR-10 from Caenorhabditis elegans. This protein was expressed in Escherichia coli, and its membrane fraction containing OR-10 coated on a quartz crystal for quartz crystal microbalance (QCM) measurements. The biosensor responded to diacetyl with a detectable concentration as low as 10−12 M [32Sung J.H. et al.Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli.Biosens. Bioelectron. 2006; 21: 1981-1986Crossref PubMed Scopus (98) Google Scholar]. However, using a crude membrane extract on the sensor surface may have distorted the response of OR-10 to VOCs due to the presence of the lipidic fraction of the membrane, as phospholipids are also known to bind odorant-like molecules [33Wu T.Z. A piezoelectric biosensor as an olfactory receptor for odour detection: electronic nose.Biosens. Bioelectron. 1999; 14: 9-18Crossref PubMed Scopus (86) Google Scholar]. Still, these reports highlighted the potential of ORs in gas sensing and the hurdles of dealing with cellular membranes for OR stabilization and immobilization. A similar approach, expressing OR-10 in human breast cancer MCF-7 cells, assessed the influence of VOCs binding to phospholipids, using control sensors analysed in parallel [34Wu C. et al.A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors.Biosens. Bioelectron. 2012; 31: 44-48Crossref PubMed Scopus (29) Google Scholar]. The controls produced very low-frequency shifts in a surface acoustic wave (SAW) as a response to the tested VOCs (diacetyl, butanone, and 2,3-pentanedione). Moreover, the response to diacetyl was the most significant with a limit of detection (LoD) of 1.2 × 10−14 M [32Sung J.H. et al.Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli.Biosens. Bioelectron. 2006; 21: 1981-1986Crossref PubMed Scopus (98) Google Scholar]. The use of a control sensor elucidated that the contribution of the affinity of VOCs to phospholipid molecules is negligible compared with their affinity to ORs, consolidating a new strategy for VOCs biosensor development. A different methodology for incorporating ORs in a gas sensor was explored using mouse ORs (mOR) in nanodiscs [35Goldsmith B.R. et al.Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins.ACS Nano. 2011; 5: 5408-5416Crossref PubMed Scopus (141) Google Scholar]. Nanodiscs with mORs were coupled to carbonnanotubes (CNTs) via His-tag interaction. In contrast with other examples where the ORs were in the membrane fraction [32Sung J.H. et al.Piezoelectric biosensor using olfactory receptor protein expressed in Escherichia coli.Biosens. Bioelectron. 2006; 21: 1981-1986Crossref PubMed Scopus (98) Google Scholar, 33Wu T.Z. A piezoelectric biosensor as an olfactory receptor for odour detection: electronic nose.Biosens. Bioelectron. 1999; 14: 9-18Crossref PubMed Scopus (86) Google Scholar, 34Wu C. et al.A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors.Biosens. Bioelectron. 2012; 31: 44-48Crossref PubMed Scopus (29) Google Scholar], in this case the nanodiscs were deposited on the sensor surface. To certify the efficiency of the nanodisc sensors, the same mORs were incorporated in digitonin micelles, deposited in CNTs, and tested for VOC sensing (Table 1). The mORs–CNT biosensors revealed broad agreement of results for the micelle and nanodisc systems. The difference observed between mOR nanodisc and micelles sensors was in their stability over time. Micelle sensors remained active for 5 days in contrast with nanodisc sensors, which were stable for 10 weeks after an initial decrease in response. The longer integrity may be due to the higher stability of the nanodisc structure in contrast to the micelles [35Goldsmith B.R. et al.Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins.ACS Nano. 2011; 5: 5408-5416Crossref PubMed Scopus (141) Google Scholar]. A human OR (hOR)-based biosensor for VOC sensing has been coupled to carboxylated polypyrrole nanotubes [36Lee S.H. et al.Mimicking the human smell sensing mechanism with an artificial nose platform.Biomaterials. 2012; 33: 1722-1729Crossref PubMed Scopus (96) Google Scholar]. Conductivity measurements revealed a very high sensitivity of this biosensor towards helional (0.02 ppt). Moreover, it presented selectivity towards helional when compared with analog VOCs like 3,4-methylenedioxy dihydrocinnamic acid, piperonal, safrole, and phenyl propanol. These analogs had at least 2/3 lower electrical resistance change upon binding to the hOR than helional in the reported biosensor measurements [36Lee S.H. et al.Mimicking the human smell sensing mechanism with an artificial nose platform.Biomaterials. 2012; 33: 1722-1729Crossref PubMed Scopus (96) Google Scholar]. The difficult, expensive, and time-consuming handling of membrane proteins may have led to the pursuit of simpler and more robust biomolecules as recognition agents [37Wu C. et al.Biomimetic sensors for the senses: towards better understanding of taste and odor sensation.Sensors (Basel). 2017; 17: E2881Crossref PubMed Scopus (13) Google Scholar]. Therefore, gas-sensing biosensors based on the soluble odorant-binding proteins (OBPs) and small peptides have gained traction [20Wasilewski T. et al.Bioelectronic nose: current status and perspectives.Biosens. Bio
Referência(s)