KR101918840B1 - Surface Enhanced Raman scattering probe comprising Surface modified Chitosan Core - Gold Shell Nanoparticle for detecting neurotransmitter - Google Patents

Abstract

The present invention relates to a surface-modified chitosan core gold-shell nanoparticle for detecting neurotransmitters and a probe for measuring surface enhanced Raman scattering comprising the same, and more particularly, to a probe for measuring the sensitivity and accuracy of measurement Improved chitosan core gold nanoparticles and probes for surface enhanced Raman scattering measurement comprising the same.
The surface modified chitosan core gold-shell nanoparticles of the present invention can stably fix the neurotransmitter material around the gold nanoparticles by chemical bonding or electrostatic adsorption, thereby enhancing the sensitivity and accuracy of the measurement.
The probe for measuring surface enhanced Raman scattering of the present invention binds to or adsorbs a neurotransmitter present at a very low concentration to provide a Raman signal, thereby increasing the sensitivity of the measurement.

Description

[0001] The present invention relates to a surface enhanced Raman scattering probe having a surface modified chitosan core gold shell nanoparticle for detecting neurotransmitters,

The present invention relates to a surface-modified chitosan core gold-shell nanoparticle for detecting neurotransmitters and a probe for measuring surface enhanced Raman scattering comprising the same, and more particularly, to a probe for measuring the sensitivity and accuracy of measurement Improved chitosan core gold nanoparticles and probes for surface enhanced Raman scattering measurement comprising the same.

Chitosan is a natural polysaccharide polymer in which β- (1-4) -2-amino-2-deoxy-D-glucopyranose units are repeated. Chitosan has been applied to the biotechnology industry, medicine, cosmetics, agriculture and the like because it has non-toxic, biodegradable, polyvalent anionic, antibacterial and biocompatible properties.

Surface Enhanced Raman Scattering (SERS) is a method of detecting and biochemically analyzing chemicals due to its high sensitivity.

Raman scattering refers to the process of scattering while losing or obtaining energy due to the vibration and rotational energy of the particles, and emits a unique spectrum depending on the chemical. However, because of its small size, the surface enhancement method is used to increase the scattering.

The surface enhancement method refers to the enhancement of Raman scattering around the surface of metal nanoparticles by using a plasmonic phenomenon occurring in metal nanoparticles. At this time, the metal particles generally used are gold (Au) nanoparticles and silver (Ag) nanoparticles.

On the other hand, selective and sensitive detection of neurotransmitters is required in the field of brain chemistry. The sensor design, which measures in the active area of these neurotransmitters, provides real-time information for effective treatment. There are many approaches to detecting neurotransmitter levels such as HPLC, capillary electrophoresis, electrochemical and optical methods.

Patent No. 10-1629569, filed and registered by the present inventor in 2014, relates to a probe for surface enhancement Raman scattering measurement for detecting neurotransmitters. The present invention provides an apparatus and method for detecting a neurotransmitter using an optical fiber-based Raman system of a chitosan-metal nanocomposite. The surface enhancement Raman scattering uses a phenomenon in which the Raman signal of the molecule is increased when molecules are present in the vicinity of the metal nanoparticles. However, since the above patent does not adsorb or fix the neurotransmitter around the metal nanoparticles, There was a limit to enhance the sensitivity and accuracy of the measurement.

The present invention provides chitosan core gold-shell nanoparticles that can increase the sensitivity and accuracy of neurotransmitter measurement.

The present invention provides a probe for surface enhanced Raman scattering measurement capable of more accurately measuring the concentration of a neurotransmitter through Raman signal measurement.

In one aspect,

Preparing a chitosan nanoparticle by mixing a cross-linking agent with a chitosan solution,

Adding a gold colloid solution to a solution containing the chitosan nanoparticles to adhere the gold to the outer surface of the chitosan nanoparticles, adding a gold salt and a reducing agent to the product-containing solution obtained in the gold particle adhering step, A coating step of forming the gold nanoparticles on the outer surface of the nanoparticles, and a modification step of reacting the chitosan nanoparticles formed with the gold-shell layer with a solution containing the compound of the formula do.

[Chemical Formula 1]

HS- [CH _2] n-COOH

Where n is an integer from 1 to 10.

In another aspect,

A step of coating the surface of the optical fiber with an aldehyde group, attaching the chitosan nanoparticles to the surface of the optical fiber using the aldehyde group, coating the surface of the chitosan nanoparticles with a gold shell layer, And then reacting the resultant solution with a solution prepared by adding a surfactant to the solution.

The surface modified chitosan core gold-shell nanoparticles of the present invention can stably fix the neurotransmitter material around the gold nanoparticles by chemical bonding or electrostatic adsorption, thereby enhancing the sensitivity and accuracy of the measurement.

The probe for measuring surface enhanced Raman scattering of the present invention binds to or adsorbs a neurotransmitter present at a very low concentration to provide a Raman signal, thereby increasing the sensitivity of the measurement.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic illustration of a method for preparing the surface-modified chitosan core gold-shell nanoparticles of the present invention.
2 is a schematic diagram showing the structure of a probe for measuring the neurotransmitter surface-enhanced Raman scattering of the present invention.
3 is an embodiment of the Raman signal detecting apparatus of the present invention.
Fig. 4 shows the results of DLS analysis of chitosan core gold-shell nanoparticles.
5 is an SEM photograph of chitosan nanoparticles (3a) and gold-coated chitosan nanoparticles (3b).
6 shows XRD results of the chitosan-gold shell nanoparticles of Example 1. Fig.
FIG. 7 is a Raman spectrum of the chitosan core gold nanoshell modified with MPA.
FIG. 8 is a photograph of Raman spectrum of chitosan core gold nanoshell after injecting and reacting with different amount of GABA.
Figure 9 is a photograph of the Raman spectrum of a chitosan core gold nanoshell and signal intensity as a function of Gaba concentration.
10 shows the Raman spectrum of the chitosan core gold nanoshell of Comparative Example 1 as a function of Gaba concentration.

The present invention provides a method for preparing surface-modified chitosan core gold-shell nanoparticles. Embodiments of the present invention will be described in detail. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic illustration of a method for preparing the surface-modified chitosan core gold-shell nanoparticles of the present invention.

Referring to Figure 1, the method of the present invention comprises chitosan nanoparticle preparation, gold particle attachment, coating and modification.

The chitosan nanoparticles are prepared by mixing a cross-linking agent in a chitosan solution.

The chitosan which can be used in the method of the present invention is not particularly limited. For example, not only chitosan dissolved in a dilute acid as described above but also modified chitosan derivatives is included.

In addition, chitosan powder can be used by dissolving in a solvent.

The chitosan may have a weight average molecular weight of 1,000 to 2,000,000, preferably 5,000 to 500,000.

The crosslinking agent may be any known crosslinking agent capable of crosslinking chitosan. For example, an aldehyde, a polyphosphate salt, preferably sodium tripolyphosphate (TPP) may be used as the crosslinking agent.

For example, when sodium tripolyphosphate (TPP) is added to a chitosan solution, the polymer chitosan can be cross-linked with a crosslinking agent to become nanoparticles.

In the step of adhering gold particles, a gold colloid solution is added to a solution containing the chitosan nanoparticles to attach gold to the outer surface of the chitosan nanoparticles.

The step of attaching gold particles is a step of attaching gold to the chitosan nanoparticles. The step of attaching gold particles is a step of attaching gold colloid or gold particles to the outer surface of the chitosan core to form a non-uniform gold layer. Referring to FIG. 1, gold particles are nonuniformly bonded and fixed on the surface of the chitosan polymer before gold particles uniformly surround the entire chitosan particle surface. The expression that gold particles are adhered or fixed nonuniformly refers to the fact that gold particles are connected to each other so that they do not form a layer and are irregularly located on the surface or gold particles are connected to each other to form a layer, It is not coated in height or surface state, but partly coated.

For example, in the step of attaching the gold particles, the chitosan core obtained in the step of producing the chitosan core may be dispersed in a solvent such as water, and a gold colloid solution may be added thereto to effect the reaction.

In the gold particle adhering step, there is no particular limitation on the content of the gold colloid to be added. For example, a gold colloid solution (5 ml solution containing 1 wt% gold colloid) is added to the 0.2 wt% chitosan core solution (25 ml), and the mixture is stirred at room temperature for about 1 hour. The gold colloid may be a THPC-induced gold colloid (tetrakishydroxymethyl phosphonium chloride-inducec gold colloid).

The method may include filtering the gold-attached chitosan nanoparticles after performing the gold-attaching step.

The coating step is a step of uniformly forming a gold layer on the outer surface of the chitosan core by inserting a gold salt and a reducing agent into a chitosan core-containing solution in which gold is non-uniformly coated.

The coating step may include forming a uniform gold layer while the gold surrounds the chitosan core, and the chitosan core may be condensed and reduced in size by the coating step.

In the coating step, a gold salt is used and ionized gold ions are reduced from the gold salt to bind the gold particles to the surface of the chitosan.

The inventors of the present invention have found that it is difficult to form a uniform gold layer when a coating step is performed without the step of attaching gold particles, and it takes considerable time even if a uniform gold layer is formed. The inventor of the present invention understands that the non-uniform gold layer (or irregularly embedded gold particles) formed through the gold particle deposition step functions as a seed in the coating step.

Furthermore, the inventors of the present invention found that the size of the nanoparticles was slightly increased due to the binding of gold in the step of adhering gold particles, but the particle size of chitosan was remarkably decreased by the coating step. Strong ionic bonding between the chitosan core and the gold shell appears to affect grain size reduction.

The gold salt (gold precursor) used in the coating step is selected from the group consisting of chloro (trimethylphosphine) gold (AuClP (CH 3) 3), potassium tetrachloroaurate (KAuCl 4), sodium chloroaurate (NaAuCl 4) ), Gold sodium bromate (NaAuBr4), gold chloride (AuCl), chloride (III) (AuCl3) or gold bromide (AuBr3).

The reducing agent may be ascorbic acid, ammonium hydroxide, NaBH4, LiAlH4, H2 / Pd-C, H2 / Ni or H2 / Pt, preferably two ascorbic acid and ammonium hydroxide It is effective to use.

 The coating step comprises adding the filtered nanoparticles, for example, 1 wt% of a gold salt solution, 10-50 [mu] l of 10-30 wt% reducing agent and 10-40 [mu] l of 10-40 wt% ammonium hydroxide .

There is no particular limitation on the ratio of the content of the filtered nanoparticles to the gold salt. For example, the filtered nanoparticle gold salt may be added in a weight ratio of about 1: 0.1 to 1.

Further, the present invention can repeat the above coating step twice or more under the same conditions.

 The modification step is a step of reacting the chitosan nanoparticles formed with the gold shell layer in a solution containing the compound of the formula (1).

[Chemical Formula 1]

HS- [CH _2] n-COOH

 Where n is an integer from 1 to 10.

More preferably, the compound of Formula 1 may be 3-Mercaptopropionic acid.

In addition, the compound of Formula 1 that can be used in the present invention may be a branched or branched hydrocarbon compound having 1 to 10 carbon atoms having a carboxyl group and a thiol group.

The thiol group of the compound of the formula (1) is bonded to the gold shell surface, and the carboxyl group can be bonded to the neurotransmitter.

The modifying step may be carried out at a weight ratio (MPA: chitosan: MPA) of 1: 0.5 to 10, preferably 1: 2 to 6: 1 by weight of MPA to the chitosan powder (added at the time of preparing the chitosan nanoparticles).

The present invention relates to chitosan core gold shell nanoparticles prepared by the method described above. 2, the chitosan core gold shell nanoparticles 120 include a chitosan core 121, a gold shell layer 122, and a compound 123 of the following formula (2).

The size of the chitosan core 121 is 100 to 500 nm, but may be reduced to about 50 to 120 nm through the coating step.

The thickness of the gold shell layer 122 may be 3 to 10 nm.

The compound (123) of the following general formula (2) may be attached to the gold shell layer.

(2)

-S- [CH _2] n-COOH

That is, as shown in Figure 1, the chitosan-gold core shell nanoparticles of the present invention has a chitosan core _{-Au-S- [CH 2] n} -COOH structure.

The compound of Formula 1 may be injected into the chitosan core-containing solution to form the compound of Formula 2 in the gold shell layer.

For the above-mentioned chitosan core gold-shell nanoparticles, reference may be made to the above-mentioned method for producing chitosan core gold-shell nanoparticles.

In the present invention, chitosan is adhered to an optical fiber by coating an optical fiber having a merit such as miniaturization, low cost, and remote measurement and having an advantage that a simple optical system can be used, To prepare a probe for Raman scattering measurement.

Referring to FIG. 2, the neurotransmitter-detecting probe 100 of the present invention includes an optical fiber 110 and a surface-modified chitosan core gold-shell nanoparticle 120 attached to the surface of the optical fiber.

Referring to FIG. 2, chitosan nanoparticles 120 are attached to the side surface of the optical fiber 110 based on the optical fiber 110.

An optical fiber is a type of thin glass or plastic fiber that carries a light signal and consists of a central area called a core and a cloth called a clad that surrounds the core. When a light from a light source such as a laser or a light bulb enters one end of the optical fiber, the light propagates through the core while the clad hits the inside surface of the optical fiber. At the other end, the light is detected by a photodetector or a human eye.

The optical fiber of the present invention uses a core portion from which a clad portion is removed.

The optical fiber core of the present invention is surface-modified to facilitate attachment of the chitosan nanoparticles 121. For example, the surface of the optical fiber may be surface modified with an aldehyde group that reacts with amine groups of chitosan. The surface modification of the surface of the optical fiber with an aldehyde group may be performed by a known method.

For example, the surface of the optical fiber surface-modified with the aldehyde group or the amine group, preferably the aldehyde group, is more hydrophilic than the pure optical fiber, so that the surface of the optical fiber is easily bonded to the chitosan particles. That is, the surface of the optical fiber surface modified with aldehyde has a high polarity, so that a polar-polar covalent bond with an amine group of chitosan is possible.

The chitosan nanoparticles 120 are attached along the optical fiber surface. More specifically, the chitosan nanoparticles may be bonded to the aldehyde group and fixed on the surface of the optical fiber.

The optical fiber 110 is surface-modified with an aldehyde group.

As described above, the surface-modified chitosan core gold-shell nanoparticles 120 include the chitosan nanoparticles 121, the gold shell layer 122, and the compound represented by the above-described formula (2).

The chitosan nanoparticles 121 are bonded to the surface of the optical fiber in combination with the aldehyde group.

The gold shell layer 122 is coated on the surface of the chitosan nanoparticles.

The gold-shell layer 122 amplifies the Raman signal when the neurotransmitter binds to the compound represented by Formula 2 above.

The gold shell layer may be formed by the above-described gold particle attachment step and coating step.

A compound of the following formula 2 is attached to the surface of the gold shell layer.

(2)

-S- [CH _2] n-COOH

 Where n is an integer from 1 to 10.

The compound attached to the surface of the gold shell layer may be a branched or branched hydrocarbon compound having 1 to 10 carbon atoms having a carboxyl group and a thiol group, as well as the compound of the formula (2).

The thiol group of Formula 1 is bonded to the gold shell surface, and the carboxyl group can be bonded to the neurotransmitter.

The compound of Formula 2 may be formed by adding 3-Mercaptopropionic acid, which binds strongly to gold.

The neurotransmitter may be selected from the group of histamine, dopamine, epinephrine, norepinephrine, serotonin, melatonin, phenylethylamine, tyramine, tryptamine, octopamine and gammaaminobutyric acid (GABA).

In another aspect, the present invention relates to a method for preparing a probe for detecting neurotransmitters.

The manufacturing method of the present invention includes an optical fiber surface modification step, a chitosan nanoparticle attachment step, a gold shell layer coating step, and a chitosan modification step.

The step of modifying the surface of the optical fiber is a step of modifying the surface of the optical fiber with an aldehyde group so as to facilitate bonding with chitosan.

In the step of attaching the chitosan nanoparticles, the chitosan nanoparticles are attached to the surface of the optical fiber using the aldehyde group. The surface of the optical fiber is modified with APTMS to produce an amine group on the surface of the optical fiber and modified with glutaraldehyde to produce an aldehyde group. The aldehyde group of the modified optical fiber and the amine group of the chitosan particle are bonded to each other to modify the chitosan particle-modified optical fiber.

The above-mentioned contents can be referred to for the chitosan nanoparticle adhering step, gold shell layer coating step and chitosan modification step. For example, in the gold-shell layer coating step, an optical fiber, a metal salt, and a reducing agent to which the chitosan nanoparticles are attached are put into an aqueous solution and coated with electroless plating. As the electroless plating method, a known method may be used.

The step of modifying the chitosan is a step of reacting the compound of Formula 1 with a solution immersed in an optical fiber (to which the chitosan core gold-shell nanoparticles are attached).

In another aspect, the present invention includes a Raman signal detection apparatus including the probe. 3 is an embodiment of the Raman signal detecting apparatus of the present invention. 3, the Raman signal detecting apparatus includes the probe 100 for detecting a neurotransmitter, the optical wavelength irradiating apparatus 200, and the signal detecting unit 300.

The probe for detecting the neurotransmitter can be referred to above.

The optical wavelength irradiating device 200 and the signal detecting unit 300 can use known devices. The optical wavelength irradiating apparatus 200 may include a laser irradiator 210, a bandpass filter 220, a beam splitter 230, or a focusing lens 240. Also, the signal detecting apparatus 300 can use a known detector capable of continuously receiving a signal and exhibiting a Raman spectrum without any particular limitation.

The bandpass filter 220 is also called a bandpass filter, and is a filter that passes only signals between specific frequencies. The frequency range through which the band pass filter 220 passes is referred to as a band pass. Only the laser passing through the band-pass filter 220 can reach the optical fiber-based chitosan-metal nanocomposite material 100. The beam splitter 230 is a device for separating the optical path of the laser output from the laser irradiation device 210 into two or more directions. The focusing lens 240 is a device for collecting the laser, .

When the Raman light is irradiated to the optical probe 100 by the optical wavelength irradiating apparatus 200, the metal layer of the probe enhances and emits an intrinsic spectrum according to the specific neurotransmitter bound thereto. The signal detector 300 can sense and display the Raman spectrum.

3, the Raman signal detecting apparatus includes a beam splitter 230 and a focusing lens 240 via a bandpass filter 220. The laser beam emitted from the laser irradiator 210 passes through a bandpass filter 220, And irradiated with a probe 100 for surface-enhanced Raman scattering measurement combined with a neurotransmitter. The light wavelength irradiated by the probe causes surface enhanced Raman scattering (SERS) through a probe 100 for measuring surface enhanced Raman scattering combined with the neurotransmitter to detect the level of the neurotransmitter through the signal detector 300.

The present invention provides a method for measuring the concentration of a neurotransmitter using a Raman signal detecting apparatus.

The method of the present invention comprises the steps of: inserting a probe for surface-enhanced Raman scattering measurement as described above into a measurement object containing a neurotransmitter; measuring Raman signal by irradiating the probe with Raman light; And calculating the concentration of the substance.

The method of measuring the Raman signal can be performed using the Raman signal detection apparatus described above.

In calculating the concentration of the neurotransmitter, a mathematical expression showing the correlation between the Gaba concentration and the peak intensity is derived as shown in FIG. 8B and FIG. 9B described below. The Gabor concentration can be calculated from the peak intensity.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

Example  One

Preparation of chitosan nanoparticles

0.105 g of chitosan powder was dissolved in 30 mL of water (containing 42 L acetate). The mixture was stirred at 60 DEG C and 1500 rpm for about one hour. On the other hand, 0.027 g of TPP was added to 25 mL of water and stirred at room temperature for about 5 minutes. After cooling the chitosan solution at room temperature, all of the chitosan solution was slowly added to the TPP solution. After stirring for about one hour, about 50 ml of the solution was centrifuged at 5500 rpm for 20 minutes to separate the precipitate. The size of chitosan nanoparticles was analyzed by dynamic light scattering (DLS).

gold Nano shell  coating

First, 1.0 g of gold (III) -chloride hydrate was added to 50 mL of water to prepare a gold solution. 0.018 g of anhydrous K2CO3 was dissolved in 25 ml of water, and 1.3 ml of gold solution was added thereto to form a gold salt solution.

The chitosan nanoparticles thus obtained were placed in 15 ml of water and 5 ml of THPC (tetrakishydroxymethyl phosphonium chloride-inducec gold colloid) -induced gold colloid solution and stirred for about 1 hour. The precipitate was then centrifuged. The precipitate was dispersed in 15 ml of water and then filtered with a microfilter having a size of about 0.45 mu m. Next, 5 ml of a gold hydrate salt solution, 30 L of ammonia water and 30 L of ascorbic acid were added to the final solution and stirred. Finally, a solution having chitosan nanoparticles surrounded by gold shells can be obtained.

Chitosan-Gold Nano-shell  Modification

Different amounts of MPA (0.1-1.0 mL) were added to solutions with chitosan nanoparticles surrounded by gold shells, respectively. After stirring for 2 hours, the impurities were separated by centrifugation.

GABA and  reaction

By changing the amount of GABA in the chitosan solution in which core-shell nano-particle-containing modified with O.5mL MPA was added to (2.0x10 ^-4 mol in the range 0.1x10 ^-4 mol) was stirred for two hours. The resulting solution was analyzed by Raman spectroscopy.

Comparative Example  One

As in Example 1, preparation of chitosan nanoparticles and gold nanoshell coating were carried out. Subsequently, the content of GABA was reacted in the range of 0.5 × 10 ^-2 mol to 0.3 × 10 ^-1 mol, respectively, without modifying the gold surface.

Fig. 4 shows the results of DLS analysis of chitosan core gold-shell nanoparticles. As shown in FIG. 4, when the chitosan nanoparticles are crosslinked with TPP, they have a uniform size of about 120 nm. When the nanoparticles are coated with a gold nanoshell, the particle size is reduced from 120 nm to 72 nm. In addition, when the gold shell layer was repeatedly coated, the size of the particles was further increased by the coated gold layer.

5 is an SEM photograph of chitosan nanoparticles (3a) and gold-coated chitosan nanoparticles (3b). Referring to FIG. 5, it can be seen that the coated 3b nanoparticles have a more uniform size and shape than the chitosan nanoparticles 3a.

Fig. 6 shows XRD results of chitosan-gold nanoparticles. Referring to FIG. 6, it can be seen that the gold shell is present because the main peak is about 40 °.

FIG. 7 is a Raman spectrum of the chitosan core gold nanoshell modified with MPA. Spectral results are shown for each case when the volume of MPA changes from 0.1 to 1.0 ml. The peak at 256 cm ^{- 1} 2 shows a very strong S-Au bond (a bond between S and gold at the MPA end). On the other hand, at the other end of the MPA molecule, a carboxyl group appears (showing a peak of about 450 cm ^-1 ). The 788 cm ^-1 wavelength peak shows the residual S phase of MPA.

The optimal MPA volume is when the residual S peak is the smallest. The graph shows the lowest peak at 0.5 mL. That is, the optimum MPA volume is 0.5 mL.

The reaction with GABA was carried out with chitosan core gold shell nanoparticles modified by adding 0.5 mL of optimal MPA. FIG. 8 is a photograph of Raman spectrum of chitosan core gold nanoshell after injecting and reacting with different amount of GABA.

FIG wavelength peak of 1610cm ^-1 8a represents the COO- ion and amino ionic bonding (i.e., 1610cm ^{- 1} wavelength of MPA COO ^-. Im). Referring to the 1610 cm ^-1 wavelength peak, as the amount of GaAs increases, the peak intensity also increases, which is shown by the following equation (b in FIG. 8). y = 3305.8X + 3352.3 (R ² = 0.9501)

As shown in FIG. 8B, the adsorption amount of Gaban and the peak intensity are linearly proportional to each other. The tendency of the adsorption amount of Gaba to be constant by the MPA (linear proportional) shows that the bond between the carboxyl group of MPA and the amino group of GABA is very solid.

9 is a photograph of a Raman spectrum of a chitosan core gold nanoshell showing a peak at 504 cm < -1 ^{& gt;} wavelength. The wavelength of 504 cm ^-1 represents the stretch vibration of the Gabacaboxyl group. The carboxyl group vibration of MPA is 1610 cm ^-1 wavelength band. If the amount of Gaba is too large, no MPA carboxyl group remains at 504 cm ^-1 wavelength.

The vapor intensity at 504 cm ^-1 wavelength is due to the carboxyl group of GABA. This proves that the gas barrier is adsorbed to the modified gold shell layer. As the amount of Gabor increases, this peak intensity increases linearly (Fig. 9b).

^{y = 5309.7x + 6744.7 (R 2} = 0.9929).

8B and 9B, the amount of adsorbed GABA can be determined by measuring the Raman spectral peak intensity.

10 shows the Raman spectrum of the chitosan core gold nanoshell of Comparative Example 1 as a function of Gaba concentration. The 496 cm ^-1 wavelength in FIG. 10 shows the carboxyl group vibration of GABA in Comparative Example 1. There is a slight difference in comparison with the Gabacarboxylic group wavelength (504 cm ^-1 ) in FIG. 9 (which shows that in Example 1, Gaba is bonded to MPA, but Comparative Example 1 is a difference due to the direct binding of Gaba to the gold shell ).

In the graph of Comparative Example 1 (FIG. 10), the Raman signal intensity is not linearly proportional to the Gaba concentration increase, but the graph of Example 1 (FIG. 9) is linearly proportional to the Gabor concentration and Raman signal intensity. In Comparative Example 1 was 5 × 10 ^- man have a lower limit of detection ³ mo, the present invention represents the detection limit of 1 × 10 ^-5 mol. That is, since the chitosan core gold nanoshell of the present invention is surface-modified with MPA, it can provide very high reliability and accuracy as a neurotransmitter detection 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 exemplary embodiments.

Claims (11)

delete delete delete delete delete An optical fiber surface-modified with an aldehyde group;
Chitosan nanoparticles attached to the surface of the optical fiber in association with the aldehyde group;
A gold shell layer coated on the surface of the chitosan nanoparticles; And
A probe for detecting a neurotransmitter comprising a compound represented by the following formula (2) attached to the surface of the gold shell layer,
When the probe is inserted into a measurement object including the neurotransmitter, the amine group of the neurotransmitter is chemically bonded to the carboxyl group of the compound represented by the following formula (2) to fix the neurotransmitter on the surface of the gold shell layer,
The neurotransmitter is at least one selected from the group of histamine, dopamine, epinephrine, norepinephrine, serotonin, melatonin, phenylethylamine, tilamine, tryptamine, octopamine and gammaaminobutyric acid (GABA)
The thickness of the gold shell layer is 3-10 nm, the total size of the chitosan nanoparticle-gold shell layer is 50-120 nm,
Wherein the gold shell layer generates a Raman signal when Raman light is irradiated to the probe.
(2)
-S- [CH _2] n-COOH
Where n is an integer from 1 to 10. [7] The probe for detecting neurotransmitter according to claim 6, wherein the compound of Formula 2 is formed of 3-Mercaptopropionic acid which binds strongly to gold.

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