Patent Application
20240110887
This application is based upon and claims the benefit of priority from Japanese Patent Application No. 2022-147971, filed Sep. 16, 2022, the entire contents of which are incorporated herein by reference.
Embodiments described herein relate generally to a sensor device that detects an acetyl compound.
An acetyl compound which is an organic compound having an acetyl group such as diacetyl, for example, diacetyl is included in alcoholic beverages, fermented beverages, dairy products, meats, and the like. A sensor device capable of relatively easily detecting these acetyl compounds is required.
An object of the present invention is to provide a sensor device capable of relatively easily detecting an acetyl compound such as diacetyl.
In general, according to one embodiment, a sensor device that detects an acetyl compound is provide.
A sensor device according to one embodiment is a sensor device that detects an acetyl compound in a sample. The sensor device includes a storage unit that stores a sample. The sensor device further includes a sensor section that comes into contact with the sample in the storage unit and detects a change in ion density, and an amino compound fixed to the sensor section. The sensor section detects a change in ion density based on a reaction between an acetyl group and an amino group. A sensor device according to one or more embodiments includes a substrate, a sensitive film provided on the substrate, a first electrode connected to one end of the sensitive film, a second electrode connected to another end of the sensitive film, and an amino compound fixed to the sensitive film.
In one or more embodiments, the sensor device further includes a supply mechanism for supplying the sample to the storage unit.
In one or more embodiments, the sensor section detects a change in ion density as a change in pH value, a change in potential or current. The change in pH value can be detected with a pH meter. The change in potential or current can be detected by a field effect transistor (FET) such as an ion selective field effect transistor (ISFET) or a graphene field effect transistor (graphene FET), a charge coupled device (CCD), or the like.
In one or more embodiments, the sensor section has a graphene FET structure in which a graphene film constitutes a channel region. An amino compound having one or more amino groups is fixed to the surface of the graphene film.
In one or more embodiments, the amino compound includes a cyclic aromatic amino compound. The cyclic aromatic amino compound has an aromatic moiety fixed to the surface of the graphene film by π-π interaction and a functional moiety having an amino group bonded to the aromatic moiety. Such a cyclic aromatic amino compound may be 1-pyrenebutyric acid hydrazide. The aromatic moiety is, for example, pyrene. The functional moiety is, for example, butyric acid hydrazide. The functional moiety can include, for example, a hydrazine structure containing an amino group, a hydrazone structure, a hydrazide structure and substituted structures thereof. As for the amino group, an amino compound having (—NR—NH2) (R is any substituent, for example, a carbon substituent or H) structure strongly reacts with an acetyl compound. In one or more embodiments, the amino compound has two or more amino groups and has an amino group at each of two adjacent carbon atoms. Since an amino group reacts with two acetyl groups of diacetyl to cyclize with each of two carbon atoms, the product is stabilized. The functional moiety of such an amino compound may be ortho-phenylenediamine. Two adjacent carbon atoms may be two adjacent carbon atoms in one aromatic ring or two carbon atoms bonded by a double bond in an alkenyl having two amino groups in cis position. For example, when an ortho-phenylenediamine structure or a diaminoalkenyl (—CNH2═CRNH2) structure and diacetyl react with each other, an aromatic cyclic structure is formed in the product, so that the product is stabilized (see, as an example, Formula 2 below).
When the sensor section has a graphene FET structure, the cyclic aromatic amino compound can be fixed to the surface of the graphene film by π-π interaction. The amino compound does not need to be an aromatic compound as long as it is fixed to the surface of the graphene film. The amino compound may be adsorbed to the graphene film by π electrons of the double bond, or may be fixed by covalent bonding or electrostatic bonding with the graphene film.
In one or more embodiments, the sample in the storage unit is in an acidic state. When the sample is in an acidic state, the amino group (—NH2) of the amino compound fixed to the surface of the graphene film is protonated (—NH3+).
In one or more embodiments, each of the one or more amino groups is in a form protected by a protecting group. Such a protecting group may be a chloro group, a butoxycarbonyl group, a benzyloxycarbonyl group, a fluorenylmethyloxycarbonyl group, a trichloroethoxycarbonyl group, an allyloxycarbonyl group, a phthaloyl group, or a toluenesulfonyl group. When the amino group is protected by the protecting group, the sensor section is stabilized for a long period of time. The amino group and the protecting group are condensed, for example. The protecting group is removed in an acidic environment (for example, a sample in the storage unit which is in an acidic state). The amino group released by the removal of the protecting group is protonated as described above.
In one or more embodiments, the sample coexists with a Schiff base in the storage unit. The Schiff base may be, for example, sodium cyanoborohydride (SCB). In one or more embodiments, the sample coexists with the amino group-modified charge-labeled molecule in the storage unit.
In one or more embodiments, the sample is in a liquid form in the storage unit.
In one or more embodiments, the sample is in a gaseous form in the storage unit.
Hereinafter, some embodiments will be described with reference to the drawings. Each drawing is a schematic view for facilitating understanding of the embodiment, and shapes, dimensions, ratios, and the like thereof do not necessarily coincide with actual ones, but those skilled in the art can appropriately set and change the shapes, dimensions, ratios, and the like in consideration of the following description and known techniques.
As described in detail below, in the sensor device 10, the sensor section has a graphene FET structure.
The sensor device 10 includes a substrate 11. The substrate 11 has, for example, a rectangular plate shape. The substrate 11 is formed of, for example, silicon, glass, ceramics, a polymer material, metal, or the like. The size of the substrate 11 is not limited, and is, for example, 1 to 10 mm×1 to 10 mm×0.1 to 0.7 mm (width×length×thickness).
The substrate 11 may include, for example, an insulating film (not shown) on the surface 11a side. Such an insulating film can be formed of, for example, an electrical insulating material such as silicon oxide, silicon nitride, aluminum oxide, a polymer material, or a self-assembled film of organic molecules.
On the surface 11a of the substrate 11, a graphene film 12 is formed as a sensitive film. The graphene film 12 is a single-layer graphene film having a thickness corresponding to one carbon atom, but can be formed of a plurality of layers of graphene. The size of the graphene film 12 is not limited, but can be, for example, 0.1 to 500 μm×0.1 to 500 μm (width×length). Practically, when the size is 10 to 100 μm×10 to 100 μm, production is easy.
A source electrode 13 is provided on the surface 11a of the substrate 11 so as to be connected to one end of the graphene film 12. A drain electrode 14 is provided on the surface 11a of the substrate 11 so as to be connected to another end of the graphene film 12.
The source electrode 13 and the drain electrode 14 are formed of, for example, a metal such as gold (Au), silver (Ag), copper (Cu), palladium (Pd), platinum (Pt), nickel (Ni), titanium (Ti), chromium (Cr), or aluminum (Al), or a conductive substance such as zinc oxide (ZnO), indium tin oxide (ITO), indium gallium zinc oxide (IGZO), or a conductive polymer.
The source electrode 13 and the drain electrode 14 are electrically connected to a power supply (not shown). In the source electrode 13 and the drain electrode 14, for example, when a voltage (source-drain voltage (Vsd)) is applied from the power supply, a current (source-drain current (Isd)) flows from the source electrode 13 to the drain electrode 14 via the graphene film 12. At this time, the graphene film functions as a channel with respect to the source electrode 13 and the drain electrode 14.
A peripheral wall 15 is erected on the surface 11a of the substrate 11. The peripheral wall 15 surrounds the graphene film 12 and covers the outer peripheral surfaces of the source electrode 13 and the drain electrode 14. The peripheral wall 15 defines a storage unit 15a that stores a sample therein. The graphene film 12 constitutes the bottom of the storage unit 15a.
The peripheral wall 15 is formed of an electrically insulating material, for example, a polymer substance such as an acrylic resin, polyimide, polybenzoxazole, an epoxy resin, a phenol resin, polydimethylsiloxane, or a fluororesin, an inorganic insulating film such as silicon oxide, silicon nitride, or aluminum oxide, a self-assembled film of organic molecules, or the like.
A lid body 16 that is supported by the peripheral wall 15 and seals the storage unit 15a is provided. The lid body 16 can be formed of the insulating material as described above.
On the surface 12a of the graphene film 12, an amino compound 17 having one or more amino groups 17a is fixed. When the amino compound 17 is a cyclic aromatic amino compound having one or more aromatic rings (for example, a benzene ring), the amino compound can be immobilized on the surface 12a of the graphene film 12 by π-π interaction with the graphene film 12. One example of such an amino compound is 1-pyrenebutyric acid hydrazide having a condensed aromatic ring and having one amino group. Another example of such an amino compound is an ortho-phenylenediamine compound (ortho-phenylenediamine or a derivative thereof) in which an amino group is bonded to each of two adjacent carbon atoms in a benzene ring. The other amino compounds (for example, diaminoalkenyl or the like) have already been described above.
The one or more amino groups 17a may each be in a form protected by a protecting group. Such protecting groups have already been described above.
The sensor device 10 detects the presence/absence of an acetyl compound in a sample (liquid sample) in the form of a solution. Therefore, the sensor device 10 further includes the liquid sample supply mechanism 110 that supplies the liquid sample to the storage unit 15a.
The liquid sample supply mechanism 110 includes a first container (bottle) 112 containing a liquid sample 111, which is a liquid sample supply source installed to be separated from the peripheral wall 15. One end of a thin tube 113 is inserted into the liquid sample 111 in the bottle 112. Another end of the thin tube 113 penetrates the lid body 16 and is inserted into the storage unit 15a. The thin tube 113 sends the liquid sample 111 in the bottle 112 to the storage unit 15a. The thin tube 113 may be formed of, for example, a material such as glass, and the inner surface of the thin tube 113 may have hydrophilicity. The liquid sample introduced into the storage unit 15a is a direct detection target sample and is denoted by reference numeral 18 (
Capillary phenomenon can be used for supplying the liquid sample 111 in the bottle 112 into the storage unit 15a via the thin tube 113. When the capillary phenomenon is used, the inner surface of the thin tube 113 preferably has hydrophilicity. A stopcock 114 that opens and closes a flow path in the thin tube 113 is interposed in the thin tube 113.
After the detection is completed, the liquid sample 18 in the storage unit 15a is discharged by the liquid sample discharge mechanism 120. The liquid sample discharge mechanism 120 includes a second container 121 that collects the discharged liquid sample, installed to be separated from the peripheral wall 15. One end of a thin tube 122 is inserted into the second container 121. Another end of the thin tube 122 penetrates the lid body 16 and is inserted into the liquid sample 18 in the storage unit 15a. The thin tube 122 is formed of, for example, a material such as glass, and the inner surface of the thin tube 122 can have hydrophilicity. Capillary phenomenon can be used for discharging the liquid sample 18 in the storage unit 15a into the second container 121 via the thin tube 122. When the capillary phenomenon is used, the inner surface of the thin tube 113 preferably has hydrophilicity. A stopcock 123 that opens and closes a flow path in the thin tube 122 is interposed in the thin tube 122.
The use of the stopcock 114 and the stopcock 123 will be obvious to those skilled in the art.
Acetyl compounds such as diacetyl to be detected are included in alcoholic beverages, fermented beverages, dairy products, meats, and the like. The sensor device 10 can detect an acetyl compound contained in such a product. If the analysis target is a liquid itself such as alcoholic beverage or fermented beverage, it can be introduced into the first bottle 112 as the liquid sample 111. When the analysis target is in a state of air, exhalation, or a gas generated from a living body, a solid product (raw meat or the like), or the like, or a gas such as air around a solid product, or the like, the gas is blown into a solvent that dissolves the acetyl compound, and the obtained solution can be introduced into the first bottle 112. For example, diacetyl is soluble in water, alcohols, ethers, or mixtures thereof.
Meanwhile, although not shown in
The fixation of the amino compound on the graphene film 12 can be performed, for example, by introducing a solution obtained by dissolving the amino compound in an aqueous solution of an alcohol (for example, isopropyl alcohol) (amino compound fixing solution) into the storage unit 15a to bring the solution into contact with the graphene film 12. As long as the amino compound in the solution has one or more aromatic rings (for example, benzene rings), the amino compound is fixed to the surface 12a of the graphene film 12 by π-π interaction as described above.
When the amino compound is fixed on the graphene film 12, the amino compound fixing solution is discharged from the storage unit 15a, and then an acid such as hydrochloric acid is introduced into the storage unit 15a. Then, the amino group of the amino compound fixed on the graphene film 12 is protonated to be —NH3+. At that time, Id (drain current)−Vg (gate voltage) in the graphene FET is measured. For example, the local minimum value of Id is read, and the numerical value is reported as charge neutral point (CNP) (first CNP).
Next, a liquid sample is introduced, and if an acetyl compound is present in the liquid sample, the ion density in the amino compound is decreased by a reaction:
R—NH2++R′—COCH3R—NHCCH3(OH)—R′+H+ (Formula 1)
In any case, Id (drain current)−Vg (gate voltage) in the graphene FET after the liquid sample 18 is introduced into the storage unit 15a is measured, the local minimum value thereof is read, and the numerical value is reported as charge neutral point (CNP) (second CNP).
When there is no substantial difference between the first CNP value and the second CNP value, it can be determined that no acetyl compound is present in the sample 18. On the other hand, when there is a substantial difference between the first CNP value and the second CNP value, it can be determined that an acetyl compound is present in the sample 18.
Incidentally, the reaction product produced according to Formula 1 is dehydrated to produce Schiff base: R—N═CCH3. This generated Schiff base is hydrolyzed in an aqueous medium to return to the original R—NHCCH3(OH)—R′ (reversible reaction), and the measurement (detection) becomes unstable. Therefore, when the Schiff base is simultaneously introduced when introducing the liquid sample into the storage unit 15a, the reversible reaction can be inhibited, and stable measurement becomes possible. As the Schiff base, for example, sodium cyanoborohydride (SCB) can be used.
In addition, after the reaction between the amino compound and the acetyl compound in the storage unit 15a, a charge-labeled molecule modified with an amino group can be added to the reaction liquid in the storage unit 15a. In such an amino group-modified charge-labeled molecule, when the amino compound has one amino group and an acetyl compound having a plurality of acetyl groups (for example, diacetyl) is present in the sample, one amino group of the amino compound reacts with one acetyl group of the acetyl compound having a plurality of acetyl groups, but the remaining acetyl groups remain as they are. The remaining acetyl group is bound to the amino group-modified charge-labeled molecule, and the amino compound is charge-labeled. When an acetyl compound having only one acetyl group (for example, acetaldehyde) coexists in the sample, the acetyl compound reacts with an amino compound, and the charge of the amino compound disappears. Therefore, when the CNP value (second CNP value) at that time is compared with the first CNP value and there is a significant difference therebetween, it is found that the difference is based on the acetyl compound having a plurality of acetyl groups. That is, it is possible to detect only the acetyl compound having a plurality of acetyl groups in the sample. Examples of such a charge-labeled compound include a peptide in which the C-terminus containing one polar amino acid is modified so as not to react with an amino group. In addition, an aptamer, an antibody, or the like that captures a charge-labeled amino compound can also be used.
Incidentally, when the amino compound to be fixed to the graphene film 12 has one or more aromatic rings (for example, a benzene ring), the amino compound can be fixed to the surface 12a of the graphene film 12 by π-π interaction as described above. As such a compound, a compound having one amino group like 1-pyrenebutyric acid hydrazide can be used as described above. However, when the cyclic aromatic amino compound has an amino group at each of two adjacent carbon atoms in one aromatic ring, a ring structure is generated by a reaction with an acetyl compound having a plurality of acetyl groups such as diacetyl. An example of the generation reaction is shown below (the following Formula 2), taking as an example a case where the cyclic aromatic amino compound is ortho-phenylenediamine and the acetyl compound having a plurality of acetyl groups is diacetyl.
The reaction of Formula 2 is an irreversible reaction, unlike the reversible reaction shown above. Then, when the acetyl compound having a plurality of acetyl groups (for example, diacetyl) and the acetyl compound having only one acetyl group (for example, acetaldehyde) coexist in the liquid sample, acetaldehyde can react with only one of the two amino groups of ortho-phenylenediamine, and the reaction is eventually a reversible reaction as described above, and the amino group of ortho-phenylenediamine reacted with acetaldehyde returns to a cationized amino group (—NH3+) by the reversible reaction. Therefore, if the CNP value (second CNP value) at that time is significantly different from the first CNP value (CNP value before reaction with an acetyl compound) as described above, it can be confirmed that diacetyl is present in the sample.
The sample in a gaseous form can, for example, cationize the amino compound by utilizing moisture in the air. In that case, the amino compound is preferably protected with an ion dissociative protecting group. Examples of such a protecting group include a chloro group which is removed from an amino group to become a chloride ion. The ion dissociative protecting group is separated from the amino group of the amino compound to become an anion, thereby making the ion concentration constant and contributing to stable detection.
Here, a method for detecting an acetyl compound using the sensor device shown in
First, a predetermined amino compound is dissolved in an amino compound-soluble solvent (for example, an alcohol aqueous solution), and the obtained amino compound solution is introduced into the storage unit 15a and allowed to stand as it is to fix the amino compound to the surface 12a of the graphene film 12.
Next, the solution of the acetyl compound is discharged from the storage unit 15a, and then an acid such as hydrochloric acid is introduced into the storage unit 15a, and the CNP value (first CNP value) is determined in this state.
After the measurement, the acid is discharged from the storage unit 15a.
Thereafter, the sample for which the presence or absence of the acetyl compound is to be detected is dissolved in an acetyl compound-soluble solvent such as alcohol, and the obtained acetyl compound solution is introduced into the storage unit 15a and allowed to stand as it is to sufficiently carry out the reaction between the amino compound and the acetyl compound. In this case, if necessary, a Schiff base may coexist in the acetyl compound solution.
Next, after the reaction liquid in the storage unit 15a is discharged, an acid such as hydrochloric acid is introduced into the storage unit 15a, and the CNP value (second CNP value) is determined in this state. At this time, the amino group-modified charge-labeled molecule may be simultaneously added into the storage unit 15a.
As described above, the CNP value is a numerical value obtained by measuring Id (drain current)−Vg (gate voltage) in the graphene FET and reading the local minimum value thereof.
Next, experimental examples will be described.
The sensor device shown in
Next, after hydrochloric acid was discharged from the storage unit 15a, a sample solution containing 200 μM of diacetyl and 2 μM of sodium cyanoborohydride (SCB) was introduced into the storage unit 15a and allowed to stand for 30 minutes. Thereafter, the sample solution was discharged from the storage unit 15a, then 0.001 M hydrochloric acid was introduced into the storage unit 15a, and Id-Vg was measured. The local minimum value thereof was read and found to be 247.57 mV (second CNP value).
It is clear that there is a significant difference (difference: 17.71 mV) between the first CNP value and the second CNP value, and it is found that diacetyl could be detected by this experiment.
An experiment was performed in the same manner as in Experimental Example 1 except that a 10 mM ortho-phenylenediamine (o-PDA) solution was used instead of the 10 mM 1-PH solution, and 0.001 M hydrochloric acid used twice was changed to 0.01 M hydrochloric acid.
The first CNP value was 228.50 mV, and the second CNP value was 258.50 mV.
It is clear that there is a significant difference (difference: 30 mV) between the first CNP value and the second CNP value, and it is found that diacetyl could be detected by this experiment.
While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel embodiments described herein may be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the embodiments described herein may be made without departing from the spirit of the inventions. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the inventions.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2022-147971 | Sep 2022 | JP | national |
