KR101511036B1 - Nano Plasmonic bio-sensor - Google Patents

Abstract

The present invention relates to a nanoplasmonic bio-sensor of a plasmonic nanostructure, and more specifically, to a nanoplasmonic bio-sensor which can significantly improve a stimulus sensing function by adjusting vertical spacing among metal nanostructures included in the sensor and by amplifying a local surface plasmonic resonance phenomenon, guarantee selective detection of chemical/biological substances, and sense reproduction of the sensor.

Description

[0001] Nano Plasmonic bio-sensor [0002]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chemical and biosensor in the form of a plasmonic nanostructure, and more particularly, to a chemical and biosensor in the form of a plasmonic nanostructure, Dimensional plasmonic nanostructure-type nanoplasmonic biosensor using a thermosensitive polymer for scattering.

Local surface plasmon resonance is induced by conductive nanoparticles or metal nanostructures of a size smaller than the wavelength of incident light, and this resonance phenomenon has the effect of amplifying the electromagnetic field around the nanostructure.

Surface-enhanced Raman scattering (SERS) using nanoplasmonic bio-substrates of metal nanostructures with local surface plasmon resonance in the visible and near-infrared regions has recently been developed for the detection of very fine chemical / I am interested.

This signal enhancement technique using metal nanostructures is an important factor in signal reinforcement, which increases the number of local electromagnetic field hot spots and amplifies the electromagnetic field strength by closely contacting specific molecules to be detected in the vicinity of the local electromagnetic field integration region Side is being considered.

Recently, in the field of optical sensors, studies have been actively conducted to use a stimulus-responsive polymer, which is a polymer substance that undergoes phase change by external stimuli such as heat, light, electric field, magnetic field, Optical sensors in which metal nanoparticles are bonded or metal nanoparticles are embedded in a polymer matrix have been developed.

Accordingly, it is desired to fabricate a biosensor in which the surface enhanced Raman scattering is improved by applying such a stimulus-sensitive polymer and metal particle to a nanoplasmonic chemical / bio substrate, but it is desired to increase the number of local electromagnetic field accumulation areas (hot spots) Reproducibility has been a problem in bringing a specific molecule to be detected close to the periphery of an electromagnetic field integration area (hot spot).

SUMMARY OF THE INVENTION The present invention has been made in order to solve the above-mentioned problems, and it is an object of the present invention to provide a high-sensitivity nanoplasmonic sensor having improved surface enhanced Raman scattering by amplifying local surface plasmon resonance phenomenon by adjusting vertical intervals between metal nanostructures And to provide a biosensor.

Also, in order to increase the efficiency of surface enhanced Raman scattering, it is not necessary to select sensors having different local surface plasmon resonance wavelengths according to a target material to be sensed, and the vertical interval between metal nanostructures included in one sensor is actively controlled And to provide a nanoplasmonic biosensor capable of active control of the local surface plasmon resonance wavelength.

A nanoplasmonic biosensor according to the present invention includes: a first metal nanostructure fixed on a substrate; A stimulus-sensitive polymer layer located on the first metal nanostructure and including a substance to be detected; And a second metal nanostructure that is moved by the stimulus-sensitive polymer layer.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the second metal nanostructure may be embedded in the stimulus-sensitive polymer layer.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the second metal nanostructure may be positioned above the stimulus-sensitive polymer layer.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the magnetic suscep- tive sensitive polymer layer has one surface fixed to the substrate and the first metallic nanostructure, and the thickness of the stimuli-sensitive polymer layer varies in a direction perpendicular to the substrate .

In the nanoplasmonic biosensor according to an embodiment of the present invention, the thickness of the stimulus-sensitive polymer layer may be 100 nm or less.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the first metal nanostructure or the second metal nanostructure may include metal nanoparticles, nanobars, nanoplates, nanotubes, nanoblocks, and nano- have.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the first metal nanostructure may be fixedly formed at intervals of 0.1 nm or more and 99 nm or less.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the first metal nano structure or the second metal nanostructure may be formed of gold, silver, platinum, aluminum, iron, zinc, copper, tin, And at least one selected from the group consisting of at least two kinds of alloys.

In the nanoplasmonic biosensor according to an exemplary embodiment of the present invention, the stimulable-sensitive polymer layer may have expansion or shrinkage characteristics depending on stimulation of at least one of pH, temperature (heat), electric field, magnetic field, and light Hydrogels.

In the nanoplasmonic biosensor according to an embodiment of the present invention, the detection target material may include Raman-active reporter molecules.

According to the nanoplasmonic biosensor of the present invention, it is possible to enhance the surface enhanced Raman scattering by amplifying the local surface plasmon resonance phenomenon by adjusting the vertical interval between the metal nanostructures included in the sensor.

In addition, the local surface plasmon resonance wavelength can be selectively controlled by actively controlling the vertical interval between the metal nanostructures included in the sensor.

Further, it is possible to actively control the vertical interval between the metal nanostructures included in one sensor, without the necessity of selecting different sensors having different local surface plasmon resonance wavelengths according to the target substance to be sensed, so that the local surface plasmon resonance wavelength can be actively controlled A nanoplasmonic biosensor can be manufactured.

In addition, customized sensing can be performed according to the target material to be detected, and selective detection of the chemical / biomolecule and sensing reproducibility of the sensor can be ensured.

1 to 3 are conceptual views illustrating the structure of a nanoplasmonic biosensor according to an embodiment of the present invention.
FIG. 4 is a graph showing a change in local surface plasmon resonance according to temperature stimulation of a stimulus-sensitive polymer according to an embodiment of the present invention.
FIG. 5 is a photograph for visually confirming a volume change according to a temperature stimulus (condition) of a stimulus-sensitive polymer according to an embodiment of the present invention.
FIG. 6 is a photograph of an electromagnetic wave simulation (FDTD) for explaining the difference in the local electromagnetic field integration intensity according to the interval between metal particles according to the present invention.
FIG. 7 is a graph showing a surface enhanced Raman scattering (SERS) intensity according to temperature of a nanoplasmonic biosensor according to an embodiment of the present invention.

Hereinafter, the nanoplasmonic biosensor of the present invention will be described in detail with reference to the accompanying drawings. The following drawings are provided by way of example so that those skilled in the art can fully understand the spirit of the present invention. Therefore, the present invention is not limited to the following drawings, but may be embodied in other forms, and the following drawings may be exaggerated in order to clarify the spirit of the present invention. Hereinafter, the technical and scientific terms used herein will be understood by those skilled in the art without departing from the scope of the present invention. Descriptions of known functions and configurations that may be unnecessarily blurred are omitted.

The nanoplatemonic biosensor of the present invention is a highly sensitive nanoplasmonic biosensor that dramatically improves the surface enhanced Raman scattering by amplifying the local surface plasmon resonance phenomenon by adjusting the vertical interval between the metal nanostructures included in the sensor.

Specifically, the nanoplasmonic biosensor of the present invention includes a first metal nanostructure 121 fixed on a substrate 100, a first metal nanostructure 121 disposed on the first metal nanostructure 121, and a stimulus- Layer 110 and a second metal nanostructure 125 that is moved by the stimuli-sensitive polymer layer 110. [ The nanoplasmonic biosensor of the present invention includes a first metal nanostructure 121 fixed on a substrate 100 and a second metal nanostructure 125 movable on the substrate 100. The first metal nanostructure 121 and the second metal nanostructure 125, If the vertical distance d between the second metal nanostructures 125 is variable by the stimulus-sensitive polymeric material, it is possible to carry out the method without limitation. However, it is preferable to include a sensor module type as shown in Figs. 1 to 3 as a specific embodiment.

1, the nanoplasmonic biosensor includes a first metal nanostructure 121 fixed on a substrate 100, a first metal nanostructure 121 fixed on a first metal nanostructure 121, And a second metal nanostructure 125 embedded in the stimulus-sensitive polymer layer 110 and moved by the stimulus-sensitive polymer layer 110, the stimulus-sensitive polymer layer 110 including a substance to be detected .

Alternatively, according to another embodiment of the present invention, the nanoplasmonic biosensor is disposed on the first metal nanostructure 121 and the first metal nanostructure 121 fixed on the substrate 100 as shown in FIG. 2 A stimulus-sensitive polymer layer 110 including a substance to be detected and a second metal nanostructure 125 disposed on the stimulus-sensitive polymer layer 110 and moved by the stimulus-sensitive polymer layer 110 .

The first metal nano structure 121 or the second metal nano structure 125 may be a metal including a conductor and a semiconductor and exhibiting a surface plasmon in a visible ray to an infrared ray region. According to an embodiment of the present invention, It is preferable to apply at least one or more selected alloys selected from the group consisting of gold, silver, platinum, aluminum, iron, zinc, copper, tin, bronze, brass and nickel.

Here, the first metal nanostructure 121 or the second metal nanostructure 125 may be selected from at least one of a zero-dimensional nanostructure, a one-dimensional nanostructure, a two-dimensional nanostructure, and a three-dimensional nanostructure. At this time, the 0-dimensional nanostructure may include nanoparticles containing a quantum dot, and the 0-dimensional nanostructure may be a colloid of nanoparticles, a dispersed phase of nanoparticles, regular or irregularly arranged nanoparticles . Crystallographically, the nanoparticles that make up the zero-dimensional nanostructure can be monocrystals, pseudo-monocrystals with plane defects such as twin, polycrystalline or amorphous. The nanoparticles forming the 0-dimensional nanostructure may be spherical particles, angular particles such as a tetrahedron or a cube, elongated shape particles having a long axis ratio of more than 1, such as rice grain, or porous particles. have. The one-dimensional nanostructure 121 may include one or more structures selected from a nanowire, a nanorod, a nanobelt, and a nanotube. The one-dimensional nanostructure 121 may include a nanowire, a nanorod, a nanobelt, A dispersed phase of one or more selected one-dimensional nanostructures or a structure in which such one-dimensional nanostructures are regularly or irregularly arranged over one plane or multiple planes. Crystalline, the one-dimensional nanostructure constituting the one-dimensional nanostructure 121 may be a single crystal, a pseudo-single crystal having a plane defect such as twin, a polycrystalline or an amorphous. The two-dimensional nanostructure may include one or more structures selected from a nanoplate and a nano-thick film. The two-dimensional nanostructure may be a structure in which a dispersed phase or nanoplate in which a nanoplate is dispersed is regularly or irregularly arranged The two-dimensional nanostructure may include a structure in which a nano-thick film formed on a support surface supporting the nanostructure, or a structure in which two or more nano-thick films are spaced apart or in contact with each other. Crystallographically, the nanoplate or nanofilm can be a monocrystalline, pseudo-monocrystalline with plane defects such as twin, polycrystalline or amorphous.

The metal nanostructure 120 (121, 125) may be formed of one or more selected nanostructures from the above-described zero-dimensional nanostructure, one-dimensional nanostructure, and two-dimensional nanostructure. For example, the metal nanostructure 120 (121, 125) may be a mixture of a 0-dimensional nanostructure and a 1-dimensional nanostructure, and a 0-dimensional nanostructure or a 1-dimensional nanostructure on a 2-dimensional nanostructure may be a regular or irregular And may be a form in which a 0-dimensional nanostructure is bonded to a 1-dimensional nanostructure.

The substrate 100 may include a support for supporting the metal nanostructures 120 and 121 and the metal nanostructures 120 and 121 and 125 described above. In this case, it goes without saying that the supporting body may be provided with a channel for transferring the liquid containing the detection target substance to the metal nanostructures 120 (121, 125).

However, the present invention is not limited to the above-described metal nanostructures 120, 121, and 125 of the substrate 100, and may be any substrate 100 for SERS having various structures and shapes.

At this time, the first metal nanostructures 121 are formed in a plurality, and the first metal nanostructures 121 are preferably fixed to the upper end of the substrate 100 so that the first metal nanostructures 121 are spaced apart from each other. As shown in FIG.

Here, the interval between the plurality of first metal nanostructures 121 is greater than that of the first metal nanostructure 121 or the second metal nanostructure 125 of the present invention in order to easily induce local surface plasmon resonance. It is preferable to have a smaller value. The first metal nano structure 121 or the second metal nano structure 125 according to the present invention is a nanoscale particle and the size of the first metal nanostructure 121 or the second metal nanostructure 125 121 may be fixedly formed at intervals of 0.1 nm or more and 99 nm or less.

Specifically, if the distance between the first metal nanostructures 121 is adjusted to be at least 0.1 nm or more and 99 nm or less, the surface area for contact with the detection target substance contained in the stimulable phosphorylic polymer layer 110 is increased So that a higher sensitivity can be ensured. More specifically, when the distance between the first metal nanostructures 121 is less than 0.1 nm, the area of the amplified electromagnetic field in the region surrounding the nanostructure may be extremely small, and the distance between the first metal nanostructures 121 If the distance is larger than the size of the metal nanostructure, the electromagnetic field amplification around the nanostructure may be insignificant.

In addition, the stimulus-sensitive polymer layer 110 of the nanoplasmonic biosensor of the present invention may have properties in which physical properties vary depending on a specific stimulus applied from the outside. Specifically, the stimulable-sensitive polymer layer 110 may be formed of a hydrogel having physical expansion or contraction characteristics depending on stimulation of at least one of pH, temperature (heat), electric field, magnetic field, and light. At this time, the expansion or shrinkage characteristics of the stimulable-sensitive polymer layer 110 according to the stimulus may include general swelling characteristics. More specifically, the hydrogel having such characteristics varies the entire volume by varying the amount of water by a specific stimulus applied from the outside. For example, as shown in FIG. 4, in the case of poly (NIPAAAm), which is a temperature stimulus-sensitive polymeric hydrogel, the molecular structure changes as the water molecules (H ₂ O) escape as the temperature rises and the volume due to poly (NIPAAAm) . That is, the volume tends to decrease more when the temperature is higher than when the temperature is lower, which can be confirmed from the photograph of FIG.

As specific and non-limiting examples, the hydrogel forming the stimulus-sensitive polymer layer 110 may be a poly (ethylene oxide), a poly (propylene oxide), a poly (vinyl methyl isocyanate), a poly (hydro propyl acrylate) (N-substituted acrylamides), poly (N-isopropylacrylamide), poly (N-acrylolypyrrolidines), poly (N-substituted acrylamides), cellulose derivatives such as cellulose, methylcellulose, hydroxypropylmethylcellulose, At least one selected from the group consisting of acrylic acid, methacrylic acid, methacrylic acid, methacrylic acid, acrylonitrile, acrylonitrile, acrylonitrile, acrylonitrile, acrylonitrile and acrylonitrile), poly In addition, a hydrogel constituting the stimulable-sensitive polymer layer 110 which is conventionally used may be used without limitation of the stimulus source.

In the present invention, in order to maximize the detection efficiency of the chemical / biosensor, it is preferable that one side of the stimulus-sensitive polymer layer 110 is fixedly formed on the substrate 100 and the first metal nano structure 121 side can do. The one surface of the stimulable-sensitive polymer layer 110 is fixed to the substrate 100 when the water-soluble gel, which is a substance forming the stimulable-sensitive polymer layer 110, changes its volume in response to external stimuli, To prevent the sensor from being deformed and to change only the thickness of the stimulable-sensitive polymer layer 110 in a direction perpendicular to the substrate 100.

In this case, the thickness of the stimulable-sensitive polymer layer 110 may be determined by the first metal nano structure 121 or the second metal nanostructure 125 of the present invention in order to easily induce local surface plasmon resonance and amplify the electromagnetic field, It is preferable to have a smaller value. The first metal nano structure 121 or the second metal nano structure 125 according to the present invention is a nanoscale particle and the size of the nanoparticles of the first metal nanostructure 121 or the second metal nanostructure 125 The thickness may preferably be 100 nm or less. Here, the thickness of the stimulable-sensitive polymer layer 110 is formed to be larger than that of the target substance included in the stimulable-sensitive polymer layer 110, so that the stimulable-sensitive polymer layer 110 can be embedded in the stimulable-sensitive polymer layer 110.

Specifically, when the thickness of the stimulus-sensitive polymer layer 110 is more than 100 nm, the amplification effect of the electromagnetic field formed between the first metal nanostructure and the second metal nanostructure may be insignificant. In addition, preferably, the thickness of the stimulus-sensitive polymer layer 110 is 50 nm or more and 100 nm or less, more preferably, the size of the first metal nanostructure or the second metal nanostructure is smaller than that of the nanostructure, It can be more advantageous from the side.

The Raman-active reporter molecule may be a molecule which exhibits spectroscopic activity by the excitation light of the excitation light source to be irradiated, and which generates stoke or anti-Stokes scattering by a vibration signal which changes polarizability during vibration. The Raman-active reporter molecule may be any molecule known to undergo Raman scattering. As a specific, non-limiting example, the Raman-active reporter molecule may be an organic molecule, an organic anion, an anion, a metal-organic ligand complex or an isotope.

The substance to be detected refers to a target substance to be detected using SERS spectroscopy, and may include an organic substance, an inorganic substance, a biochemical substance, or a complex thereof, including Raman-active reporter molecules. Here, the composite may include a mixture in which two or more substances selected from organic substances, inorganic substances and biochemical substances are mixed, or a combination in which two or more substances selected from organic substances, inorganic substances and biochemical substances are chemically bonded. Here, the biochemical material may include an organic matter or a drug that affects a cell constituent material, a genetic material, a carbon compound, metabolism of an organism, material synthesis, material transport or signal transmission process.

In the nanoplasmonic biosensor of the present invention configured as described above, when the magnetic pole is applied from the outside, the thickness of the magnetic polesensitive layer 110 may be reduced. The second metal nanostructure 125 may be moved toward the fixed first metal nanostructure 121 by a decrease in the thickness of the stimulrot-sensitive polymer layer 110.

The vertical distance d between the first metal nano structure 121 and the second metal nano structure 125 is thus closely aligned with the first metal nano structure 121 and the second metal nano structure 125, The number of localized electromagnetic field integration areas (hot spots) 130 in the sensor can be increased, as shown in the electromagnetic field simulation (FDTD) photograph to illustrate the difference in local electromagnetic field integration intensity according to the vertical distance d between the electrodes 125 .

The vertical distance d between the first metal nanostructure 121 and the second metal nanostructure 125 thus closely coincides with a specific molecule to be detected in the vicinity of the local electromagnetic field integration region 130 It becomes possible to amplify the electromagnetic field intensity. This can be confirmed by a graph showing the surface enhanced Raman scattering (SERS) intensity according to temperature of the nanoplasmonic biosensor according to the embodiment of the present invention shown in FIG. Specifically, a nanoplasmaic biosensor structure composed of gold (Au) nano-island / pNIPAAm polymer layer / gold (Au) nano-island is formed and the detection target material is benzene thiol, (SERS) intensity of the surface enhanced Raman scattering (SERS) was measured. As a result, it was confirmed that the surface enhanced Raman scattering (SERS) value was increased due to the close position of the gold (Au) nano islands as the pNIPAAm polymer layer shrank .

According to the embodiment described above, the nanoplasmonic biosensor of the present invention can dramatically improve the surface enhanced Raman scattering by amplifying the local surface plasmon resonance phenomenon by adjusting the vertical interval between the metal nanostructures included in the sensor according to the temperature , And it is natural that the stimulus source can be changed depending on the other stimuli-sensitive polymer employed. At this time, the stimulus-sensitive polymer and the stimulus source can be selectively adopted depending on the physical properties of the substance to be detected.

In addition, the nanoplasmonic biosensor of the present invention is capable of customized detection according to a target material to be detected, and is capable of selectively detecting a chemical / biomolecule and detecting reproducibility of the sensor.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, Those skilled in the art will appreciate that various modifications and variations can be made from such a substrate.

Accordingly, the spirit of the present invention should not be construed as being limited to the embodiments described, and all of the equivalents or equivalents of the claims, as well as the following claims, belong to the scope of the present invention .

100: substrate
110: Stimulation-sensitive polymer layer
120: metal nanostructure
121: First metal nanostructure
125: second metal nanostructure
130: Local electromagnetic field integration area (hot spot)

Claims (10)

A plurality of first metal nanostructures fixed to a substrate and spaced apart from each other;
A stimulus-sensitive polymer layer fixed by the substrate and the first metal nanostructure, the stimulus-sensitive polymer layer including a substance to be detected;
A second metal nanostructure in which a perpendicular interval between the first metal nanostructure and the first metal nanostructure is controlled by the stimulus-sensitive polymer layer;
Wherein the biosensor is a biosensor.
The method according to claim 1,
Wherein the second metal nanostructure is embedded in the stimulus sensitive polymer layer.
The method according to claim 1,
Wherein the second metal nanostructure is positioned above the stimulus-sensitive polymer layer.
delete The method according to claim 1,
Wherein the stimulable-sensitive polymer layer has a thickness of 100 nm or less.
The method according to claim 1,
The first metal nanostructure or the second metal nanostructure may include a metal nanostructure,
And a regular array structure composed of any one selected from the group consisting of a 0-dimensional nanostructure, a 1-dimensional nanostructure, a 2-dimensional nanostructure, and a 3-dimensional nanostructure.
The method according to claim 1,
Wherein the first metal nanostructure is fixed at an interval of 0.1 nm or more and 99 nm or less.
The method according to claim 1,
The first metal nanostructure or the second metal nanostructure may include a metal nanostructure,
At least one or more selected from the group consisting of gold, silver, platinum, aluminum, iron, zinc, copper, tin, bronze, brass and nickel.
The method according to claim 1,
Wherein the stimulable-sensitive polymer layer is made of a hydrogel having a swelling property by external stimulation of at least one of pH, temperature (heat), electric field, magnetic field and light.
The method according to claim 1,
Wherein the substance to be detected comprises Raman-active reporter molecules.

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