U.S. patent application number 13/169222 was filed with the patent office on 2012-07-05 for surface modified metal nano-particle and use thereof.
This patent application is currently assigned to POSTECH ACADEMY-INDUSTRY FOUNDATION. Invention is credited to Sungsook Ahn, Sung Yong Jung, Hae Koo Kim, Jin Pyung Lee, Sang Joon LEE.
Application Number | 20120168681 13/169222 |
Document ID | / |
Family ID | 46379944 |
Filed Date | 2012-07-05 |
United States Patent
Application |
20120168681 |
Kind Code |
A1 |
LEE; Sang Joon ; et
al. |
July 5, 2012 |
Surface Modified Metal Nano-Particle and Use Thereof
Abstract
The present invention provides a metal nanoparticle that is
surface-modified with a hydrophilic or hydrophobic functional
group, and a composition for optical detection comprising the same.
The surface-modified nanoparticles according to the present
invention form clusters suitable for optical detection, for
example, suitable as an X-ray contrast agent, and have surface
plasmon energy in the visible region, thereby being usefully
applied to a variety of optical detection methods.
Inventors: |
LEE; Sang Joon; (Pohang-si,
KR) ; Jung; Sung Yong; (Ulsan, KR) ; Ahn;
Sungsook; (Bucheon-si, KR) ; Lee; Jin Pyung;
(Pohang-si, KR) ; Kim; Hae Koo; (Gyeongsangbuk-do,
KR) |
Assignee: |
POSTECH ACADEMY-INDUSTRY
FOUNDATION
Pohang-city
KR
|
Family ID: |
46379944 |
Appl. No.: |
13/169222 |
Filed: |
June 27, 2011 |
Current U.S.
Class: |
252/408.1 ;
428/403; 977/773 |
Current CPC
Class: |
Y10S 436/805 20130101;
Y10T 428/2982 20150115; B82Y 20/00 20130101; Y10T 428/2991
20150115; G01N 23/00 20130101; G01N 21/554 20130101; B82Y 5/00
20130101; B82Y 15/00 20130101; G01N 21/75 20130101; Y10S 977/904
20130101; Y10S 977/902 20130101; Y10S 977/773 20130101 |
Class at
Publication: |
252/408.1 ;
428/403; 977/773 |
International
Class: |
G01N 21/00 20060101
G01N021/00; B32B 15/02 20060101 B32B015/02 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 29, 2010 |
KR |
10-2010-0138187 |
Claims
1. A surface-modified metal nanoparticle, wherein a
surface-modifying material is introduced on its surface, a particle
diameter is 1 to 100 nanometer, and the surface-modifying material
is one or more selected from the group consisting of aliphatic or
aromatic carboxylic acid having 1 to 20 carbon atoms,
pyrimidine-based bases, purine-based bases, linear or branched
alcohols having 1 to 10 carbon atoms, and alkyl groups having 1 to
50 carbon atoms.
2. The surface-modified metal nanoparticle according to claim 1,
wherein the metal particle is selected from the group consisting of
gold, silver, magnesium oxide, iron, platinum, titanium, alumina,
and zirconia.
3. The surface-modified metal nanoparticle according to claim 1,
wherein the surface-modifying material is introduced on the metal
surface through a functional group selected from the group
consisting of a thiol group, a carboxyl group, an amine group, an
aldehyde group, a ketone group, a peroxide group, an alkene group
having 3 to 500 carbon atoms, alkyl halide having 3 to 500 carbon
atoms, an ester group, an ether group, an epoxide group, a nitrile
group, and a carbonyl group.
4. The surface-modified metal nanoparticle according to claim 1,
wherein the surface-modifying material is one or more selected from
the group consisting of linear or branched alcohols having 1 to 10
carbon atoms.
5. A composition for optical detection, comprising the
surface-modified metal nanoparticle according to claim 1.
6. The composition for optical detection according to claim 5,
comprising the surface-modified metal nanoparticle in one or more
solvents selected from the group consisting of water, linear or
branched alcohol having 3 to 500 carbon atoms, aldehyde having 3 to
500 carbon atoms, ketone having 3 to 500 carbon atoms, and normal
paraffin-based solvent having 5 to 20 carbon atoms at a
concentration of 100 ppm to 10 wt %.
7. The composition for optical detection according to claim 5,
wherein the composition is used for X-ray contrast agent, UV
spectroscopy, or fluorescence analysis.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to and the benefit of
Korean Patent Application No. 10-2010-0138187 filed in the Korean
Intellectual Property Office on Dec. 29, 2010, the entire contents
of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] (a) Field of the Invention
[0003] The present invention provides a metal nanoparticle that is
surface-modified with a hydrophilic or hydrophobic functional
group, and a composition for optical detection comprising the
same.
[0004] (b) Description of the Related Art
[0005] Nanotechnology is a technology of manipulating and
controlling matters at the atomic or molecular level, and suitable
to create many new materials or devices with a vast range of
applications, such as in electronics, materials, communications,
mechanics, medicine, agriculture, energy and environment.
[0006] Currently, nanotechnology has been developed in various
fields, and is broadly classified into three kinds of major fields:
(1) nanomaterial with respect to compounding new minute matters and
raw materials, (2) nanodevice with respect to manufacturing the
device to function a fixed ability through arranging or mixing nano
matters, and (3) nano-biotechnology with respect to applying
nanotechnology to biotechnology.
[0007] In the nano-biotechnology field, nanoparticles have been
used in a broad range of applications, such as separation of
biomolecules, imaging contrast, and drug/gene delivery.
[0008] For more effective imaging contrast or detection,
nanoparticles should form clusters within a specific range of size,
have a surface plasmon in the visible region, and easily perform in
vivo flow imaging. Many studies have been made on nanoparticles
satisfying these requirements, but there have been no remarkable
results yet.
SUMMARY OF THE INVENTION
[0009] The present inventors found that metal nanoparticles are
capable of form clusters within a specific range of size when they
are surface-modified with a specific functional group, thereby
having a surface plasmon in the visible region, and easily
performing in vivo flow imaging, to complete the present
invention.
[0010] Therefore, an embodiment of the present invention provides a
metal nanoparticle that is obtained by surface-modifying it with a
hydrophilic or hydrophobic functional group, preferably a
hydrophilic functional group.
[0011] Another embodiment provides a composition for optical
detection, comprising the surface-modified nanoparticle.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0012] In the present invention, metal nanoparticles are prepared
to have a suitable size and shape, and then their surface can be
modified with various low molecular materials to show
negatively/positively charged, acidic/basic, or
hydrophilic/hydrophobic characteristics while maintaining their own
properties. Such surface-modified metal nanoparticles determine
important physical properties such as surface plasmon, and the
metal nanoparticles are introduced into synthetic/natural
microparticles to change the encapsulation efficiency.
[0013] Therefore, an embodiment of the present invention provides a
metal nanoparticle that is obtained by surface-modifying with a
hydrophilic or hydrophobic functional group, preferably a
hydrophilic functional group. More particularly, the metal
nanoparticle is characterized in that
[0014] a surface-modifying material is introduced on the surface of
a metal particle,
[0015] the diameter of the metal particle ranges from 1 to 100
nanometer, and
[0016] the surface-modifying material is one or more selected from
the group consisting of aliphatic or aromatic carboxylic acids
having 1 to 20 carbon atoms, pyrimidine-based bases, purine-based
bases, linear or branched alcohols having 1 to 10 carbon atoms, and
alkyl groups having 1 to 50 carbon atoms, preferably 1 to 20 carbon
atoms.
[0017] The metal nanoparticles may be selected from the group
consisting of gold, silver, magnesium oxide, iron, platinum,
titanium, alumina, zirconia and the like. For example, the metal
nanoparticles may be gold nanoparticles obtained by reducing a gold
salt (chloride (III) trihydrate, HAuCl.sub.4.3H.sub.2O) with sodium
citrate anhydride (e.g., sodium citrate tribasic dehydrate) or a
suitable polymer such as a poly(ethylene-co-propylene) copolymer.
The diameter of the metal nanoparticles is not particularly
limited, but for the usefulness as a contrast agent, it may be 1 to
100 nm, preferably 5 to 50 nm, and more preferably 10 to 30 nm.
[0018] The surface-modifying material is directly introduced on the
metal surface or introduced on the metal surface via a functional
group selected from the group consisting of a thiol group, a
carboxyl group, an amine group, an aldehyde group, a ketone group,
a peroxide group, an alkene group having 3 to 500 carbon atoms,
preferably 3 to 100 carbon atoms, more preferably 3 to 50 carbon
atoms, and much more preferably 3 to 20 carbon atoms, alkyl halide
having 3 to 500 carbon atoms, preferably 3 to 100 carbon atoms,
more preferably 3 to 50 carbon atoms, and much more preferably 3 to
20 carbon atoms, an ester group, an ether group, an epoxide group,
a nitrile group, a carbonyl group, and the like. For example, the
surface-modifying material linked with a thiol group as the
functional group for introduction to the metal surface may be one
or more selected from the group consisting of thioglycolic acid,
mercaptobenzoic acid, thioguanine, mercaptoethanol, propanethiol,
terphenylthiol, propenethiol, thiazolinethiol,
phenylimidazolethiol, phenylthiazolethiol, aminothiadiazolethiol,
bromobenzoxazolethiol, bromopyridinethiol, fluorobenzoxazolethiol,
methoxybenzoxazolethiol, carboranethiol, mentha-8-thiol-3-one,
1-(4-hydroxybenzyl)imidazole-2-thiol,
1-methyl-1H-benzimidazole-2-thiol, 1-phenyl-1H-tetrazole-5-thiol,
1H-1,2,4-Triazole-3-thiol, 3-amino-1,2,4-triazole-5-thiol,
4-(trifluoromethyl)pyrimidine-2-thiol,
4-amino-5-(4-pyridyl)-4H-1,2,4-triazole-3-thiol,
4-hydroxy-6-(trifluoromethyl)pyrimidine-2-thiol,
4-methyl-4H-1,2,4-triazole-3-thiol,
5-(3-pyridyl)-1,3,4-oxadiazole-2-thiol,
5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol,
5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol,
5-(4-pyridyl)-1,3,4-oxadiazole-2-thiol,
5-methyl-1,3,4-thiadiazole-2-thiol,
5-methylthio-1,3,4-thiadiazole-2-thiol,
5-phenyl-1,3,4-oxadiazole-2-thiol,
5-phenyl-1H-1,2,4-triazole-3-thiol,
7-(trifluoromethyl)quinoline-4-thiol,
1-[2-(dimethylamino)ethyl]-1H-tetrazole-5-thiol,
11-(1H-pyrrol-1-yl)undecane-1-thiol,
0-(2-carboxyethyl)-O'-(2-mercaptoethyl)heptaethylene glycol,
O-(2-mercaptoethyl)-O'-methyl-hexa(ethylene glycol),
O-[2-(3-mercaptopropionylamino)ethyl]-O'-methylpolyethylene glycol,
1-naphthalenethiol, 11-mercapto-1-undecanol, 2-thiobarbituric acid,
cysteamine hydrochloride, thiocholesterol,
1-(11-mercaptoundecyl)imidazole, spironolactone,
1-ethyltetrazole-5-thiol, 1-(3-hydroxyphenyl)-1H-tetrazole-5-thiol,
1-(2-methoxyphenyl)-4-(4-nitrophenyl)-1H-imidazole-2-thiol,
1-(3-methylphenyl)-4-(4-methylphenyl)-1H-imidazole-2-thiol
hydrobromide,
1-(4-(difluoromethoxy)benzoyl)-1,4,5,6-tetrahydrocyclopenta(D)imidazole-2-
-thiol, 1-(4-aminophenyl)-4-phenyl-1H-imidazole-2-thiol,
1-(4-aminophenyl)tetrazole-5-thiol hydrochloride,
1-(4-aminophenyl)tetrazole-5-thiol hydrochloride,
1-methyl-1H-imidazole-2-thiol, 1-methyl-1H-tetrazole-5-thiol,
1-naphthalen-2-yl-1H-tetrazole-5-thiol,
1-phenyl-1H-(1,2,4)triazole-3-thiol,
1-(methylthio)-7H-pyrrolo(2,3-D)pyrimidine-4-thiol,
2-(methylthio)-7H-pyrrolo(2,3-D)pyrimidine-4-thiol,
1-amino-5-(2-chloro-phenyl)-pyrimidine-4-thiol,
2-amino-5-(2-chloro-phenyl)-pyrimidine-4-thiol,
2-methyl-9H-purine-6-thiol, 3-O-tolyl-6-P-tolyl-pyrazine-2-thiol,
3-phenyl-1,2,4-oxadiazole-5-thiol,
4,5-bis(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4,5-dibenzyl-4H-1,2,4-triazole-3-thiol,
4,5-diphenyl-4H-1,2,4-triazole-3-thiol,
4,6-dimethyl-pyrimidine-2-thiol,
4-(2,3-dimethylphenyl)-5-methyl-4H-1,2,4-triazole-3-thiol,
4-(2,4-dimethylphenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(2,4-dimethylphenyl)-5-phenyl-4H-1,2,4-triazole-3-thiol,
4-(4-bromophenyl)-1,3-thiazole-2-thiol,
4-(4-bromophenyl)-5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(4-bromophenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(4-chlorophenyl)-1,3-thiazole-2-thiol,
4-(4-chlorophenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(4-ethoxyphenyl)-1,5-diphenyl-1H-imidazole-2-thiol hydrobromide,
4-(4-methoxyphenyl)-1-(4-methylphenyl)-1H-imidazole-2-thiol
hydrobromide,
4-(benzylideneamino)-5-(2,4-dichlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-bromophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-chlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-fluorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-furyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-methylphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(2-pyridinyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiol-
,
4-(benzylideneamino)-5-(3-chlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(3-ethoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(3-isopropoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(3-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(3-methylphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(3-pyridinyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(4-bromophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(4-fluorophenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(4-methylphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(4-tert-butylphenyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-(phenoxymethyl)-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-cyclohexyl-4H-1,2,4-triazole-3-thiol,
4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol,
4-allyl-5-phenoxymethyl-4H-(1,2,4)triazole-3-thiol,
4-amino-4H-1,2,4-triazole-3-thiol,
4-amino-5-(2,4-dichlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-amino-5-(2-bromophenyl)-4H-1,2,4-triazole-3-thiol,
4-amino-5-(2-chloro-phenyl)-pyrimidine-2-thiol,
4-amino-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-amino-5-(3-pyridinyl)-4H-1,2,4-triazole-3-thiol,
4-amino-5-(4-amino-phenyl)-pyrimidine-2-thiol,
4-amino-5-(phenoxymethyl)-4H-1,2,4-triazole-3-thiol,
4-amino-5-butyl-4H-1,2,4-triazole-3-thiol,
4-amino-5-ethyl-4H-1,2,4-triazole-3-thiol,
4-amino-5-methyl-4H-1,2,4-triazole-3-thiol,
4-benzyl-5-(2,4-dichlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-benzyl-5-(3,4-dimethoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-benzyl-5-(4-pyridinyl)-4H-1,2,4-triazole-3-thiol,
4-benzyl-5-(4-tert-butylphenyl)-4H-1,2,4-triazole-3-thiol,
4-cyclohexyl-5-(2,4-dichlorophenyl)-4H-1,2,4-triazole-3-thiol,
4-cyclohexyl-5-(2-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-cyclohexyl-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-cyclohexyl-5-(3,4-dimethoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-ethyl-5-(4-nitrophenyl)-4H-1,2,4-triazole-3-thiol,
4-ethyl-5-M-tolyl-4H-(1,2,4)triazole-3-thiol,
4-ethyl-5-phenoxymethyl-4H-(1,2,4)triazole-3-thiol,
4-methyl-6-trifluoromethyl-pyrimidine-2-thiol,
4-O-tolyl-5-P-tolyl-4H-(1,2,4)triazole-3-thiol,
4-phenyl-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiol,
4-phenyl-5-M-tolyl-4H-(1,2,4)triazole-3-thiol,
5,5'-(ethylenedithio)bis(1,3,4-thiadiazole-2-thiol),
5,5'-tetramethylenebis(4-phenyl-4H-1,2,4-triazole-3-thiol,
5,6,7,8-tetrahydro-quinazoline-2-thiol,
5,6-dihydro-4H-(1,3)thiazine-2-thiol,
5,7-bis(ethylamino)(1,2,4)triazolo(4,3-A)(1,3,5)triazine-3-thiol,
5-((1-naphthylmethyl)sulfanyl)-1,3,4-thiadiazole-2-thiol,
5-(2,4-dichloro-phenoxymethyl)-(1,3,4)oxadiazole-2-thiol,
5-(2,4-dichlorophenyl)-4-(4-methylphenyl)-4H-1,2,4-triazole-3-thiol,
5-(2,4-dichlorophenyl)-4-ethyl-4H-1,2,4-triazole-3-thiol,
5-(2-chloroethylthio)-1,3,4-thiadiazole-2-thiol,
5-(2-furyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
5-(3-chlorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazole-3-thiol,
5-(3-chlorophenyl)-4-isobutyl-4H-1,2,4-triazole-3-thiol,
5-(3-methylphenyl)-4-(4-methylphenyl)-4H-1,2,4-triazole-3-thiol,
5-(4-bromophenyl)-4-(2,4-dimethylphenyl)-4H-1,2,4-triazole-3-thiol,
5-(4-bromophenyl)-4-(2-methylphenyl)-4H-1,2,4-triazole-3-thiol,
5-(4-bromophenyl)-4-(2-methylphenyl)-4H-1,2,4-triazole-3-thiol,
5-(4-chloro-phenyl)-(1,3,4)oxadiazole-2-thiol,
5-(4-chloro-phenyl)-pyrimidine-4-thiol,
5-(4-chlorophenyl)-4-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol,
5-(4-chlorophenyl)-4-isobutyl-4H-1,2,4-triazole-3-thiol,
5-(benzylthio)-1,3,4-thiadiazole-2-thiol,
5-(butylthio)-1,3,4-thiadiazole-2-thiol,
5-(dodecylthio)-1,3,4-thiadiazole-2-thiol,
5-(ethylthio)-1,3,4-thiadiazole-2-thiol,
5-(hexylthio)-1,3,4-thiadiazole-2-thiol,
5-(pentylthio)-1,3,4-thiadiazole-2-thiol,
5-amino-1,3,4-thiadiazole-2-thiol,
5-amino-4-phenyl-4H-(1,2,4)triazole-3-thiol,
5-benzyl-4-phenyl-4H-(1,2,4)triazole-3-thiol, alkane having 3 to
500 carbon atoms, alkanethiol having 3 to 500 carbon atoms, and the
like.
[0019] The metal nanoparticles surface-modified with these
surface-modifying materials have a diameter of approximately 20 nm,
and the interparticle distance and cluster size are suitable as an
X-ray contrast agent when they form clusters in a suitable medium.
Among the surface-modifying materials, gold nanoparticles
surface-modified with a hydrophilic group (e.g., linear or branched
alcohols having 1 to 10 carbon atoms) showed most suitable
properties in flow measurements in a sap which consists mainly of
water (see FIG. 2).
[0020] Further, the gold nanoparticles according to the present
invention have a surface plasmon energy in the visible ray region
as well as in the wavelength range from several angstroms (.ANG.)
to several micrometers (.mu.m), and thus allow detection in the
visible, X-ray and UV regions (see Example 4 and FIGS. 5a to
5e).
[0021] As described above, the surface-modified metal nanoparticles
according to the present invention are useful as a composition for
optical detection, and thus, another aspect of the present
invention is to provide a composition for optical detection
comprising the surface-modified metal nanoparticles. The
composition for optical detection is characterized in that it
contains the surface-modified metal nanoparticles in one or more
solvents (or medium) selected from the group consisting of water,
linear or branched alcohols having 3 to 500 carbon atoms,
preferably 3 to 100 carbon atoms, more preferably 3 to 50 carbon
atoms, and much more preferably 3 to 20 carbon atoms, aldehyde
having 3 to 500 carbon atoms, preferably 3 to 100 carbon atoms,
more preferably 3 to 50 carbon atoms, and much more preferably 3 to
20 carbon atoms, ketone having 3 to 500 carbon atoms, preferably 3
to 100 carbon atoms, more preferably 3 to 50 carbon atoms, and much
more preferably 3 to 20 carbon atoms, and normal paraffin-based
solvent having 5 to 20 carbon atoms at a concentration of 100 ppm
to 10 wt %, preferably 100 to 10,000 ppm, and more preferably 100
to 1,000 ppm.
[0022] The normal paraffin-based solvent is those having a boiling
point of 40.degree. C. or lower, and for example, it may be one or
more selected from the group consisting of n-pentane and isomers
thereof (e.g., isopentane, neopentane, etc.), hexane, methylpentane
(e.g., 2-methylpentane, 3-methylpentane, etc.), methylbutane (e.g.,
2,3-dimethylbutane, 2,2-dimethylbutane, etc.), n-heptane and
isomers thereof (e.g., 2-methylhexane(isoheptane), 3-methylhexane,
2,2-dimethylpentane(neoheptane), 2,3-dimethylpentane,
2,4-dimethylpentane, 3,3-dimethylpentane, 3-ethylpentane,
2,2,3-trimethylbutane, etc.), octane, n-octane and isomers thereof
(e.g., 2-methylheptane, 3-methylheptane (2 enantiomers),
4-methylheptane, 3-ethylhexane, 2,2-dimethylhexane,
2,3-dimethylhexane (2 enantiomers), 2,4-dimethylhexane (2
enantiomers), 2,5-dimethylhexane, 3,3-dimethylhexane,
3,4-dimethylhexane (2 enantiomers+1 meso compound),
3-ethyl-2-methylpentane, 3-ethyl-3-methylpentane,
2,2,3-trimethylpentane (2 enantiomers), 2,2,4-trimethylpentane
(isooctane), 2,3,3-trimethylpentane, 2,3,4-trimethylpentane,
2,2,3,3-tetramethylbutane, n-nonane and isomers thereof, n-decane
and isomers thereof, n-undecane and isomers thereof, n-dodecane and
isomers thereof, n-tridecane and isomers thereof, n-tetradecane and
isomers thereof, n-pentadecane and isomers thereof, n-hexadecane
and isomers thereof, n-heptadecane and isomers thereof,
n-octadecane and isomers thereof, n-nonadecane and isomers thereof,
n-eicosane and isomers thereof, and the like.
[0023] As aforementioned, when the surface-modified metal
nanoparticles according to the present invention are included in
the solvent within the above concentration range, they can form
clusters suitable to act as an X-ray contrast agent, and surface
plasmon energy can be easily detected in the visible ray region.
Thus, it is preferable that the solvent (or medium) and
concentration are adjusted within the above range. In addition, the
surface-modifying material is as described above. Among them, when
a hydrophilic material is used as the surface-modifying material,
more excellent optical detection properties can be obtained. In the
preferred embodiment, the surface-modified metal nanoparticles
according to the present invention may be injected into the body at
a concentration of 100 to 10 wt %, preferably 100 to 10,000 ppm,
more preferably 100 to 1,000 ppm, and for example, 300 to 700 ppm
in an aqueous solution.
[0024] The composition for optical detection according to the
present invention means an agent that allows all types of optical
analysis, such as imaging and/or spectrum analysis and/or
fluorescence analysis, by measurement of in vivo optical properties
of animal or plant. It can be used for X-ray contrast, UV
spectroscopy (e.g., UV visible spectroscopy), fluorescence
analysis, or the like.
[0025] In the present invention, the surface-modifying material
forms a suitable cluster, and thus time-dependent flow motion can
be easily observed in the synchrotron X-ray (see FIG. 4a). This
property allows to easily measure time-dependent flow motion when
the surface-modifying material is applied to plant or animal bodies
(see FIG. 4b), thereby providing excellent vivo imaging
contrast.
[0026] Still another aspect of the present invention is to provide
a method for analyzing a biological sample using the composition
for optical detection.
[0027] The method may comprise the steps of injecting the
composition for optical detection into a biological sample; and
detecting optical properties obtained from the biological
sample.
[0028] The biological sample may be an animal or plant body, or a
tissue or cell isolated from animal or plant. For example, after
the composition for optical detection is injected into the
biological sample, X-ray imaging or UV spectroscopy is performed,
or a typical fluorescent material is added to the composition for
optical detection to investigate the fluorescent properties,
thereby detecting various physiological kinetic features in the
animal or plant body or in the isolated tissue or cell.
[0029] In addition, a change in surface plasmon occurs by the
surface modification according to the present invention, and the
wavelength and intensity of light absorption/emission peaks differ
depending on properties of the surface-modified material and size
of the metal particles. When the surface-modified gold
nanoparticles having X-ray absorption property are used as a
contrast agent, the surface-modified material mainly adjusts
physical properties that influence inter-particle relations. In
molecular detection using the surface plasmon properties, the
property of changing energy detection region is important as a
contrast agent. The wavelength and intensity of light
absorption/emission peaks are changed, and a specific reaction can
be monitored by observing the changes in both the wavelength and
intensity due to interactions between nanoparticles and a target to
be detected.
[0030] The metal nanoparticles of the present invention are
surface-modified with a specific surface-modifying material, and
thus they have a uniform size, and the interparticle distance and
cluster size become suitable as an X-ray contrast agent when they
form clusters in a suitable medium, and they have favorable surface
plasmon properties in a wide range of regions including the visible
region, thereby being usefully applied as a composition for optical
detection.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 is a diagram showing gold nanoparticles prepared in
Example 1;
[0032] FIG. 2a shows six types of gold nanoparticles prepared in
Example 1, and FIG. 2b shows surface plasmon properties according
to surface-modification, in which each numeral means the number of
AuNP of FIG. 1;
[0033] FIGS. 3a and 3b show particle formation characteristics in a
nanoscale (average number of particles in 200.times.200 nm.sup.2
and interparticle distance, a) and cluster formation
characteristics in a microscale (average number and size of
clusters, b) according to properties of the surface-modifying
materials of six types of gold nanoparticles prepared in Example
1;
[0034] FIG. 4a is X-ray images showing time-dependent flow motions
of AuNP5 (gold nanoparticle surface-modified with a hydrophilic
group, namely, an ethanol group) among the gold nanoparticles
prepared in Example 1, and FIG. 4b is X-ray images showing
time-dependent flow motions across xylem vessels in a rice
monitored by AuNP5 (gold nanoparticle surface-modified with a
hydrophilic group, namely, an ethanol group);
[0035] FIG. 5a shows the size of gold nanoparticles prepared by
reduction of gold metal ions with a triblock copolymer (Pluronic)
composed of poly(ethylene-co-propylene), in which (A) shows gold
nanoparticles reduced with 10 wt % of Pluronic P84, (B) shows gold
nanoparticles reduced with 30 wt % of Pluronic P84, and (C) shows
gold nanoparticles reduced with 50 wt % of Pluronic P84,
[0036] FIG. 5b shows color changes by addition of gold nanoparticle
to the amphiphilic polymer Pluronic 84 dissolved in water,
indicating surface plasmon energy in the visible region;
[0037] FIG. 5c shows the results of UV-vis spectroscopy measuring
surface plasmon energy of the particles in FIG. 5b;
[0038] FIG. 5d shows color changes by addition of AuNP 5 (among the
hydrophilic gold nanoparticles in FIG. 1) to the amphiphilic
polymer Pluronic 84 dissolved in water, indicating surface plasmon
energy in the visible region; and
[0039] FIG. 5e shows color changes by addition of AuNP 6 (among the
hydrophobic gold nanoparticles in FIG. 1) to the amphiphilic
polymer Pluronic 84 dissolved in water, indicating surface plasmon
energy in the visible region (0.1 to 0.9 marked on the test tubes
of FIGS. 5b, 5d and 5e represent the concentrations of Pluronic 84,
and 0.1 means 10% by weight, 0.2 20% by weight, 0.3 30% by weight,
0.4 40% by weight, 0.5 50% by weight, 0.6 60% by weight, 0.7 70% by
weight, 0.8 80% by weight, and 0.9 90% by weight.
EXAMPLES
[0040] Hereinafter, the present invention will be described in more
detail with reference to the following Examples. However, these
Examples are for illustrative purposes only, and the invention is
not intended to be limited by these Examples.
Example 1
Preparation of Surface-Modified Gold Nanoparticles
[0041] Gold chloride (III) trihydrate (HAuCl.sub.4.3H.sub.2O) was
dissolved in de-ionized water to prepare a solution of
1.0.times.10.sup.-3 mol/L, and 20 mL of sodium citrate tribasic
dehydrate solution in water (4.times.10.sup.-2 mol/L) was added to
200 mL of the above solution under refluxing, thereby reducing the
surface of gold particles. After refluxing for 30 min, the
temperature was reduced to 25.degree. C., and the particle size was
adjusted to approximately 20 nm. After completion of the reduction,
the final particles were dialyzed in de-ionized water overnight
using Spectra/Por.RTM.7 membrane (1,000 Da cut) to remove unreacted
impurities.
[0042] The particles prepared without additional reaction after the
reduction were designated as AuNP 1. 40 mL of 0.1 M thioglycolic
acid (SH--CH.sub.2COOH), 40 mL of 0.1M 4-mercaptobenzoic acid
(SH-Ph-COOH), 40 mL of 0.1 M 6-thioguanine
(SH--C.sub.5H.sub.4N.sub.5), 40 mL of 0.1 M 2-mercaptoethanol
(SH--CH.sub.2CH.sub.2OH), and 40 mL of 0.1 M 1-propanethiol
(SH--CH.sub.2CH.sub.2CH.sub.3) were added to 10 ml of the reduced
particle in de-ionized water (2.4.times.10.sup.18 AuNPs/m.sup.3) at
room temperature, and then reacted at 50 to 60.degree. C. for 6 to
12 hrs until there is no more change in color. After completion of
the reaction, the particles were dialyzed in de-ionized water
overnight using Spectra/Por.RTM.7 membrane (1,000 Da cut) to remove
unreacted impurities. The obtained particles were designated as
AuNP 2 (modified with SH--CH.sub.2COOH), AuNP 3 (modified with
SH-Ph-COOH), AuNP 4 (modified with SH--C.sub.5H.sub.4N.sub.5), AuNP
5 (modified with SH--CH.sub.2CH.sub.2OH), and AuNP 6 (modified with
SH--CH.sub.2CH.sub.2CH.sub.3), respectively (see FIG. 1).
[0043] Transmission electron microscopy (TEM) images (JEOL
Cs-corrected HR-TEM (JEM-2200FS)) of the obtained six gold
nanoparticles, AuNP 1, AuNP 2, AuNP 3, AuNP 4, AuNP 5, and AuNP 6
are shown in FIG. 2a. As shown in FIG. 2a, it was confirmed that
the average diameter of all gold nanoparticles was constantly
controlled in a nanosize.
[0044] In addition, the obtained six gold nanoparticles, AuNP 1,
AuNP 2, AuNP 3, AuNP 4, AuNP 5, and AuNP 6 were dissolved in
de-ionized water to prepare solutions of 2.4.times.10.sup.18
AuNPs/m.sup.3, respectively, and their absorbance according to
wavelength was measured using a UV-vis spectrometer (HP, HP8453),
and the results are shown in FIG. 2b.
[0045] As shown in FIG. 2b, the AuNPs 1 and 2 had a main peak at
524 nm, but the intensity of the peak was lower in AuNP 2,
indicating that cluster formation easily occurs in AuNP 2 compared
to AuNP 1. AuNP 3 had a main peak at 527 nm, and the main peak was
red-shifted to 529 nm in alcohol-functionalized AuNP 5. Meanwhile,
the main peaks of 6-thioguanine-functionalized AuNP 4 and
methyl-functionalized AuNP 6 were red-shifted to 537 nm with lower
intensity. The absorbance of AuNPs 5 and 6 gradually increases with
the increase in the wavelength. AuNP 5 exhibits another prominent
peak at 770 nm. Overall, it was found that the main peaks at around
.about.520 nm were peak-broadened and red-shifted due to the
surface modification with hydrophilic/hydrophobic, or acidic/basic
functional group.
[0046] As shown in FIG. 2a, the gold nanoparticles were controlled
to have the size of approximately 20 nm. However, solution
properties shown in FIG. 2b were changed by surface plasmon
according to surface modification of the gold nanoparticles.
[0047] FIG. 2b shows the absorption spectra of the AuNPs from 1 to
6 designed in the present Example that were dispersed in de-ionized
water, together with the picture images of the solutions. AuNPs 1
and 2 exhibited deep red wine color, while AuNPs 3 and 5 expressed
bluish red wine color. AuNPs 4 and 6, on the other hand, had an
apparently bluish color. The absorption was measured by a UV-vis
spectrometer (HP, HP8453). AuNPs 1 and 2 had a main peak at about
524 nm, but the intensity of the peak is lower in AuNP 2. That main
peak was found to be red-shifted to 527 nm in AuNP 3. Hydrophilic
alcohol-covered AuNP 5 shows the main peak approximately at 529 nm
with lower intensity. Meanwhile, the main peaks of
6-thioguanine-covered AuNP 4 and methyl-covered AuNP 6 were
positioned at around 537 nm with far lower intensity. The
absorption of AuNPs 5 and 6 gradually increased with the increase
in the wavelength. AuNP 5 exhibited second peak at around 770 nm.
Overall, the absorbance intensity of the main peaks (.about.520 nm)
was decreased with a peak broadening and red-shifted to higher
wavelength region, as the surface ligand becomes neutral and
hydrophobic.
Example 2
Cluster Formation of Surface-Modified Gold Nanoparticles
[0048] AuNP 1, AuNP 2, AuNP 3, AuNP 4, AuNP 5, and AuNP 6 were
dissolved in de-ionized water at a concentration of
2.4.times.10.sup.18 AuNPs/m.sup.3, respectively. Each of the
solutions was dropped on a slide glass, and dried. Their images
were obtained by scanning electron microscopy (SEM) (JEOL JSM-7401F
SEM at an acceleration voltage of 15 kV) (3a) and zone-plate X-ray
nanoscopy (3b), and shown in the upper part of FIGS. 3a and 3b. The
number described in each picture corresponds to the particle number
of FIG. 1. The average interparticle distance and average size of
the clusters in 20 predetermined areas (200.times.200 nm.sup.2 and
3.times.3 mm.sup.2) are shown in the graph of the lower part of
each figure.
Example 3
Imaging of Sap Flow Using Surface-Modified Particles
[0049] It was tested whether the physical properties of the gold
nanoparticles fabricated according to the present invention are
controlled, and thus time-dependent flow motion of the clusters can
be measured in the synchrotron X-ray. The gold nanoparticle used in
the test was AuNP 5 suggested in FIG. 1. Starting from the
concentration of 2.4.times.10.sup.18 AuNPs/m.sup.3, the
concentration was increased 10 times to reach 2.4.times.10.sup.19
AuNPs/m.sup.3. Upon converting it into a weight of 20 nm gold
nanoparticle, its concentration is 500 mg/kg H.sub.2O (500
ppm).
[0050] The flow motion of the clusters was measured using the
synchrotron X-ray. The synchrotron X-ray source was obtained from
7B2 beamline at the Pohang Accelerator Laboratory (Pohang, Korea).
Using a bending magnet, X-rays with a peak energy of 20.3 keV (8-30
keV range) were applied as a function of time without monochromator
to obtain high energy. A CdWO.sub.4 crystal was used as a
scintillator to convert the X-ray into visible wavelength. A charge
coupled device (CCD) camera was used to convert the optical
brightness into electrical signals. Time-resolved images were
captured through the Kapton film covering a sample holder at a
speed rate of 25 frames per second. Starting from the concentration
of 2.4.times.10.sup.18 AuNPs/m.sup.3, the concentration of the gold
nanoparticles was gradually increased to measure the time-dependent
flow motion. When the concentration of the gold nanoparticle
reached 2.4.times.10.sup.19 AuNPs/m.sup.3 (10 times), the flow
motion can be visualized as shown in FIG. 4a, indicating optical
intensity suitable to capture images.
[0051] The gold nanoparticles were used to track sap flow motions
in plants, and consecutive images showing the time-dependent flow
motions of the gold nanoparticles inside the xylem vessels of a
rice leaf are shown in FIG. 4b. After the concentration-controlled
gold nanoparticle (AuNP 5) solution was taken up by the rice leaf,
time-dependent images were captured using the above described X-ray
imaging technique.
[0052] More particularly, the leaf end of rice (Oryza sativa (L.)
cv Dongjin) was cut, and left for about 5 min until the xylem
vessels were dehydrated. Then, the leaf end was dipped for about 10
min in the solution of 2.4.times.10.sup.19 AuNPs/m.sup.3, which was
prepared by dissolving AuNP 5 in de-ionized water, and transport of
the gold nanoparticle solution inside the xylem vessels through the
root was observed.
[0053] The uptake of the gold nanoparticle solution inside the
xylem vessels of a rice leaf was visualized by X-ray imaging (X-ray
radiography) to observe the time-dependent flow motions of the
nanoparticles, as shown in FIG. 4b. The arrows in the images of
FIG. 4b indicate the meniscus, and flow motions have been
understood by tracing the meniscus in the conventional studies. As
shown in FIG. 4b, it was found that the sap flow motions inside the
xylem vessels (1) and (2) differ from the meniscus. (1) and (2)
represent the initial positions of the AuNP clusters and it was
observed that (1) did not move and remained stationary and only (2)
moved until 1.3 sec. (1) remained stationary due to the flow
resistances produced by a perforation plate. At the time of 1.7
sec, when pulling capacity to overcome the flow resistance was
applied, it moved again. Because of insufficient pulling capacity,
the clusters at (2) divided into (2-1) and (2-2).
[0054] This result demonstrates that the gold nanoparticles of the
present invention actually operate as an effective contrast agent
suitable for in vivo exploration.
Example 4
Surface Plasmon Energy of Surface-Modified Gold Nanoparticle in
Visible Region
[0055] A gold (III) chloride trihydrate (HAuCl.sub.4.3H.sub.2O, 0.5
g/200 mL water) solution was mixed with Pluronic 84 to prepare gold
nanoparticles by reduction.
[0056] More particularly, the gold (III) chloride trihydrate
aqueous solution (0.5 g/200 mL water) and Pluronic 84 were mixed
with each other in a weight ratio of 0.9:0.1, 0.8:0.2, 0.7:0.3,
0.6:0.4, 0.5:0.5, 0.4:0.6, 0.3:0.7, 0.2:0.8, and 0.1:0.9 (weight of
gold (III) chloride trihydrate aqueous solution:weight of Pluronic
84) to prepare gold nanoparticles by reduction of gold (III)
chloride trihydrate.
[0057] Among them, the gold nanoparticles obtained by mixing the
gold (III) chloride trihydrate aqueous solution and Pluronic 84 in
a weight ratio of 0.9:0.1 [FIG. 5a (A)], 0.7:0.3 [FIG. 5a (B)], and
0.5:0.5 [FIG. 5a (C)] are shown in FIG. 5a.
[0058] In addition, when nanoparticles were prepared by reducing
the gold (III) chloride trihydrate with various concentrations of
Pluronic 84, changes in color were shown as in FIG. 5b. The numbers
in FIG. 5b represent the weight ratio of Pluronic 84, when a total
weight of the mixture of the gold (III) chloride trihydrate aqueous
solution and Pluronic 84 is regarded as 1. As shown in FIG. 5b,
upon addition of the gold nanoparticles to the amphiphilic polymer
Pluronic 84 dissolved in water, unique color changes are shown
depending on the polymer concentration, indicating that they have
surface plasmon energy in the visible region.
[0059] In addition, the surface plasmon energy was measured at each
concentration using a UV-vis spectrometer (HP, HP8453), and the
results are shown in FIG. 5c. As shown in FIG. 5c, a weak peak was
observed at the weight ratio of Pluronic 84 of 0.1 and 0.9,
indicating that particle formation occurs unclearly or no particle
formation occurs in the measured energy region. Formation of gold
nanoparticles having surface plasmon energy in the measured region
was observed at the weight ratio of Pluronic 84 from 0.2 to
0.8.
[0060] Among the gold nanoparticles prepared in Example 1, the
hydrophilic (SH--CH.sub.2CH.sub.2OH)-covered AuNP 5 was added to
various concentrations of the Pluronic 84 aqueous solution, and the
concentration-dependent color change was observed and shown in FIG.
5d. The numbers in FIG. 5d represent the concentrations of the
Pluronic 84 aqueous solution, and are the same as in FIG. 5b. As
shown in FIG. 5d, it can be seen that the hydrophilic gold
nanoparticles according to the present invention exhibit unique
surface plasmon in the visible region within the microstructures of
various concentrations of Pluronic 84.
[0061] Among the gold nanoparticles prepared in Example 1, the
hydrophobic (SH--CH.sub.2CH.sub.2CH.sub.3)-covered AuNP 6 was added
to various concentrations of the Pluronic 84 aqueous solution, and
the concentration-dependent color change was observed and shown in
FIG. 5e. The numbers in FIG. 5e represent the concentrations of the
Pluronic 84 aqueous solution, and are the same as in FIG. 5b. As
shown in FIG. 5e, it can be seen that the hydrophobic surface
modified gold nanoparticles according to the present invention
exhibit unique surface plasmon in the visible region within the
microstructures of various concentrations of Pluronic 84.
* * * * *