KR101905975B1 - Plasmon raman probe and endoscope device using the same - Google Patents

Abstract

The present invention aims to provide a plasmon Raman probe in which metal nanoparticles for enhancing Raman signal are bonded to a probe so that metal nanoparticles are directly in contact with lesions, and an endoscope apparatus using the same. To this end, the present invention is characterized in that a plurality of metal nanoparticles are attached to the ends of multiple optical fibers for receiving a Raman signal for plasmon excitation, and the attached metal nanoparticles are brought into direct contact with the examined tissue (A) Therefore, the present invention can prevent the human body from remaining with the metal nanoparticle-added material by bonding the metal nanoparticles for Raman signal enhancement to the probe so that the metal nanoparticles are brought into direct contact with the lesion, There is an advantage that stability can be improved.

Description

TECHNICAL FIELD [0001] The present invention relates to a plasmon resonance probe,

The present invention relates to a plasmon Raman probe and an endoscope apparatus using the same. More particularly, the present invention relates to a plasmon Raman probe in which metal nanoparticles for Raman signal enhancement are bonded to a probe so that metal nanoparticles are directly in contact with a lesion, ≪ / RTI >

The endoscopic device is a medical device that non-invasively observes the interior of a living organ such as a digestive or respiratory apparatus.

The diagnostic method using the endoscope is a photodynamic diagnosis method, for example, in cancer diagnosis, invasive biopsy is a method of extracting a living tissue and culturing cancer tissue, It is a technique to diagnose by irradiating a suspicious part with light by using an endoscope without extracting the tissue. Therefore, there is no pain in the patient, and it is convenient and easy to perform the procedure because the image is used. In addition, the cancer diagnosis and the cancer can be detected early.

Conventional endoscopy is performed by observing mucous membranes using white light, and it is possible to detect minute lesions of the order of several millimeters by expressing a slight color change of the mucous membrane in a natural color.

On the other hand, endoscopic examination by such white light is not sufficient in terms of, for example, cognitive ability of dysplasia of dysplastic lesion occurring in Barrett's esophagus or differential diagnosis of tumor and non-tumor of polyp.

Therefore, biopsy and histopathologic examination of separate tissues are required to determine the degree of benign or malignant tissue. However, in addition to the above-mentioned problems in the case of tissue harvesting, sampling errors, So that the cost and the inspection time are increased.

In fact, such a white light using endoscopic examination method is merely a relatively simple screening technique, so-called " endoscopic imaging " (hereinafter, referred to as " endoscopic imaging ") in which an endoscope irradiates artificial light in vivo to extract / endoscopic imaging " as used herein.

In order to overcome these problems, fluorescence imaging technology, which is an endoscopic imaging technique using fluorescence, has been proposed, which is basically a fluorescence imaging method in which a living tissue irradiated with a laser beam of a specific frequency emits fluorescence, A technique that injects a photosensitizer or a bio marker to identify abnormal tissues and normal tissues from the fluorescence emitted therefrom.

By using such fluorescence imaging technology, it is possible to analyze the presence or absence of the target substance in real time and more accurately with respect to the sample in the living body.

Raman scattering is a scattering light having an optical characteristic that is different from the energy of incident light due to molecular vibrational motion. Especially, the Raman scattering has a narrow line width and a different scattering wavelength depending on the kind of scattering molecule and vibration.

In addition, Raman markers that express Raman scattering light do not exhibit the optical backbone characteristic such as fluorescence.

Using such an optical characteristic, it is possible to encode a large number of different signals within a certain optical measurement area, thus enabling signal detection for a plurality of biomarkers (multiple targets) in a single diagnosis, and using such Raman spectroscopy , And has the potential to perform diagnosis of tissues based on molecular structure.

Raman spectroscopy is a method of obtaining the frequency of molecules in a tissue by irradiating monochromatic light onto a tissue (cell) using a Raman effect in which the frequency of scattered light changes by the number of molecules in the tissue.

FIG. 1 is a block diagram showing a configuration of a Raman signal detecting apparatus according to the related art. Referring to FIG. 1, there is shown a conventional Raman signal detecting apparatus, which includes a light source 10 for outputting light in a predetermined wavelength range, a light receiver 20, a plurality of optical fibers 21 (Not shown), an optical unit 30, and a light separation unit 40.

The path of the optical signal collected by the optical fiber bundle 20 and passed through the optical fiber bundle 21 and the optical section 30 is separated into path 1 and path 2 in the optical splitting section 40, (For example, the area where labeled particles are bound to target cells and tissues), and the type and relative amount of labeled particles from various Raman signals spectrally separated by path 2, .

However, the Raman signal is very weak in the intensity of the Raman signal emitted from the tissue itself, and most Raman signals interfere with the self fluorescence emitted from the tissue, and the Raman spectrum difference between the abnormal region and the normal region is minimal. Raman spectroscopy has yet to be used for accurate diagnosis.

To solve these problems, Surface-Enhanced Raman Scattering was developed to amplify Raman spectroscopic signals using plasmon resonance phenomenon of metal nanoparticles.

For medical use, cancer can be diagnosed by analyzing the Raman signal generated by irradiating a laser with a plasmon resonance frequency by adsorbing a substance (fluorescent dye, DNA, etc.) with metal nanoparticles added to the lesion.

FIG. 2 is a diagram illustrating a detection process of a Raman scattering signal according to the related art. In FIG. 2, the metal nanoparticles 61 are externally added with a fluorescent material 62, and the metal nanoparticles 61 are adsorbed on the lesion 50 The metal nanoparticles 61 injected into the human body are adsorbed on the lesion 50 so that the light collecting unit 20 irradiates the laser 11 And receives the generated Raman signal 12.

However, such a conventional technique has a problem that a functional group must be coated on a material to which metal nanoparticles are added for each lesion so that the material to which the metal nanoparticles are added may be adsorbed on the lesion.

In addition, there is a problem that it is difficult to confirm the stability of the substance due to the possibility that the substance to which the metal nanoparticles are added after the diagnosis is left in the human body.

Korean Patent Registration No. 10-1207695 entitled "Method for simultaneous detection of fluorescence and Raman signals for fluorescence and Raman signal targets and medical imaging apparatus for simultaneous detection of targets using the same"

In order to solve these problems, the present invention aims to provide a plasmon Raman probe in which metal nanoparticles for Raman signal enhancement are bonded to a probe so that metal nanoparticles are directly in contact with lesions, and an endoscope apparatus using the same.

According to an aspect of the present invention, there is provided a plasma processing apparatus including a plurality of metal nanoparticles for exciting plasmons at the ends of a plurality of optical fibers for receiving a Raman signal, the metal nanoparticles having an electric field locally increased (Plasmonic hot spot) is generated, and when the metal nanoparticles are in direct contact with the examined tissue (A), the Raman signal is detected.

The probe according to the present invention may further include a laser guide unit for guiding the laser beam into the metal nanoparticles to amplify the Raman signal.

Further, the laser guide unit according to the present invention is characterized in that a part of the optical fiber bundles of the multiple optical fiber units are connected to a laser beam for generating a Raman signal.

In addition, the laser guide unit according to the present invention is separated from the optical fiber bundle of the multiple optical fiber unit, and the laser beam is incident on the side surface.

The probe according to the present invention may further include a laser incidence part installed between the multiple optical fiber part and the metal nanoparticles and configured to transfer the laser beam incident from the laser guide part to the metal nanoparticles.

The probe according to the present invention may further include a reflector disposed on at least one side of the laser incidence portion and reflecting the laser beam radiated to the side of the laser incidence portion toward the metal nanoparticle.

In addition, the laser incidence unit according to the present invention is characterized by comprising a GRIN lens or any combination of lenses for transmitting an image of the subject A to the multiple optical fibers.

The probe according to the present invention may further include an illumination optical fiber for outputting illumination light transmitted from the outside in order to acquire an image of a lesion.

The metal nanoparticles according to the present invention are characterized in that the distance d2 between the metal nanoparticles is less than the diameter d1 of the metal nanoparticles in order to generate plasmonic hot spots.

The metal nanoparticles according to the present invention may be any one of silver (Ag), gold (Au), aluminum (Al), copper (Cu), platinum (Pt), and palladium .

Further, the metal nanoparticles according to the present invention are characterized in that an insulator is coated on the periphery.

The insulator according to the present invention is characterized in that the thickness is 100 nm or less.

In addition, the metal nanoparticles according to the present invention may further include a Raman display material emitting a Raman signal.

The present invention also provides an endoscope apparatus comprising: a plurality of metal nanoparticles for exciting plasmons are provided at the ends of a plurality of optical fibers for receiving a Raman signal, the metal nanoparticles having a plasma A plasmon Raman probe configured to generate a plasma hot spot and to detect a Raman signal when the metal nanoparticles are in direct contact with the examined tissue (A); and a plasmon Raman probe, wherein the plasmon Raman probe And an endoscope head for outputting the received signal to an external device.

The endoscope according to the present invention is characterized in that the plasmon Raman probe performs switching control so as to selectively receive any one of a Raman signal or an image signal obtained by measuring the subject's tissue (A).

Further, the plasmon Raman probe according to the present invention is installed so as to be drawn out from the endoscope head part by a predetermined length.

The endoscope head according to the present invention may further include a working channel unit for sampling or treating a sample of the subject's tissue.

The endoscope head according to the present invention may further include a light source for outputting illumination for measurement of the tissue under test A and an image receiver.

The present invention relates to a metal nanoparticle for enhancing the Raman signal, which is bonded to a probe so that the metal nanoparticle is brought into direct contact with the lesion, thereby preventing human body residue of the material to which the metal nanoparticle is added, There are advantages.

1 is a block diagram showing a configuration of a conventional Raman signal detecting apparatus.
BACKGROUND OF THE INVENTION 1. Field of the Invention [0001]
3 is an exemplary view showing a first embodiment of the plasmon Raman probe according to the present invention.
FIG. 4 is a cross-sectional view of a BB section of a plasma Raman probe according to the first embodiment of FIG. 3; FIG.
Fig. 5 is an exemplary view showing a second embodiment of the plasmon Raman probe according to the present invention. Fig.
FIG. 6 is a cross-sectional view of a CC section of a plasma Raman probe according to the second embodiment of FIG. 5;
7 is an exemplary view showing a third embodiment of the plasmon Raman probe according to the present invention.
8 is a cross-sectional view showing a configuration of a distal end of a plasma Raman probe according to the present invention.
9 is a perspective view showing an embodiment of a distal end of a head of an endoscope apparatus having a plasma Raman probe according to the present invention.
10 is a perspective view showing another embodiment of the end of the head of an endoscope apparatus having a plasma Raman probe according to the present invention.

Hereinafter, preferred embodiments of a plasmon Raman probe and an endoscope apparatus using the same will be described in detail with reference to the accompanying drawings.

(Embodiment 1)

FIG. 3 is a view showing a first embodiment of a plasma Raman probe according to the present invention, and FIG. 4 is a sectional view showing the structure of a plasma Raman probe according to the first embodiment of FIG.

3 and 4, the plasma Raman probe 100 according to the present invention includes a plurality of metal nanoparticles (not shown) for plasmon excitation at the ends of the multiple optical fibers 110 receiving the Raman signal The laser light incident part 120, the laser guide part 130, the metal nanoparticle 140, and the metal nanoparticle 140. [ Nanoparticles 140, and an insulator 150.

The laser incidence part 120 is installed at the end of the multiple optical fiber part 110 so that the incident laser beam is transmitted to the metal nanoparticles 140 when the laser beam output from the laser guide part 130 is incident. do.

The laser incidence part 120 is a combination lens that combines various lenses such as a GRIN lens or a ball lens, a convex lens, and a concave lens for transmitting the image of the examined tissue A to the multiple optical fiber part 110 And the multiple optical fiber unit 110 to which the laser incidence unit 120 is bonded can be used as an image probe.

The laser guide unit 130 may include a metal nanoparticle 140 attached to the laser incidence unit 120 for amplifying the Raman signal and a laser beam output from the laser light source unit may be incident on the laser incidence unit 120 .

The laser guide unit 130 may include a plurality of optical fiber bundles together with the plurality of optical fibers 110 and an optical fiber positioned inside the bundle of the plurality of optical fibers 110 may be formed of a laser guide 130 do.

The metal nanoparticles 140 are attached to the ends of the laser incidence part 120 through electrostatic or chemical bonding and are attached to the attached metal nanoparticles 140 Is directly in contact with the specimen (A).

8, the distance d2 between the metal nanoparticles 140 and the neighboring metal nanoparticles 140a is less than the diameter d1 of the metal nanoparticles 140, Thereby facilitating the generation of locally maximized plasmonic hot spots.

The metal nanoparticles 140 may be any one selected from the group consisting of silver (Ag), gold (Au), aluminum (Al), copper (Cu), platinum (Pt), and palladium Lt; / RTI >

The metal nanoparticles 140 may further include a Raman display material that emits a Raman signal. Preferably, the metal nanoparticles 140 include a fluorescent dye, a quantum dot, a BRET, a dye-doped silica And the like, so that the fluorescence signal and the Raman signal can be detected at the same time.

The metal nanoparticles 140 are disposed on the circumference of the metal nanoparticles 140 to prevent vibrational information of the examined tissue A from being distorted when the metal nanoparticles 140 are in direct contact with the examined tissue A. [ 150).

The insulator 150 is formed of a material selected from Si, Al, Mg, Zr, Pb, Ba, B and Ca, and the insulator 150 is formed to have a thickness of 100 nm or less.

The probe 100 according to the present embodiment may further include a reflector 160 that reflects a laser beam emitted toward the side of the laser incidence portion 120 toward the metal nanoparticles 140 have.

That is, the reflector 160 is coated on one side of the laser incidence part 120 or on the entire surface of the laser incidence part 120, and a part of the laser beam incident on the laser incidence part 120, Is reflected toward the metal nanoparticles 140 so that the efficiency of the laser beam incident on the metal nanoparticles 140 can be increased.

The probe 100 may further include an illumination optical fiber 170 for transmitting external light for imaging when the multiple optical fiber unit 110 to which the laser incidence unit 120 is bonded is used as an imaging probe Can be configured.

(Second Embodiment)

FIG. 5 is a view illustrating a second embodiment of a plasma Raman probe according to the present invention. FIG. 6 is a sectional view showing the structure of a plasma Raman probe according to the second embodiment of FIG. And the same reference numerals are used for the same constituent elements.

As shown in FIGS. 5 and 6, the plasma Raman probe 100a according to the second embodiment includes a plurality of metal nano-tubes (not shown) for plasmon excitation at the ends of the multiple optical fibers 110 receiving the Raman signal, The laser light incident portion 120, the laser guide portion 130, and the laser light guide portion 130 are attached so that the attached metal nanoparticles 140 are directly contacted to the subject A, , Metal nanoparticles (140), and an insulator (150).

The plasma Raman probe 100a according to the second embodiment is different from the probe 100 according to the first embodiment in the arrangement of the laser guide part 130. [

The laser guide unit 130 according to the second embodiment may be configured such that the laser beam output from the laser light source unit (not shown) is incident on the laser incidence unit 120 by the metal nanoparticles 140 attached to the laser incidence unit 120, And the laser guide unit 130 may be formed of a plurality of optical fiber bundles together with the plurality of optical fibers 110. The optical fiber positioned outside the bundles of the plurality of optical fibers 110 may be a laser And a guide 130.

The probe 100a according to the second embodiment includes a reflection unit 160 that reflects a laser beam emitted toward the side of the laser incidence unit 120 in the direction of the metal nanoparticles 140, An optical fiber 170 for transmitting external light for imaging may be further included when the multiple optical fiber unit 110 to which the optical fiber 110 is bonded is used as an imaging probe.

(Third Embodiment)

7 is a view illustrating a third embodiment of the plasma Raman probe according to the present invention. Repeated description of the same components as those of the probe according to the first embodiment will be omitted, and the same reference numerals will be used for the same components use.

7, the plasmon Raman probe 100b according to the third embodiment includes a plurality of metal nanoparticles 140 (not shown) for plasmon excitation at the ends of the multiple optical fibers 110 receiving the Raman signal, The laser light incident part 120, the laser guide part 130, and the metal nano particles 140 so that the attached metal nanoparticles 140 are in direct contact with the examined tissue A. [ Particles 140, and an insulator 150.

The plasma Raman probe 100b according to the third embodiment is different from the probe 100 according to the first embodiment in the arrangement of the laser guide part 130. [

That is, the laser guide unit 130 according to the third embodiment is configured as a separate channel different from the multiple optical fiber unit 110, and the laser beam output from the laser guide unit 130 is incident on the laser incidence unit 120 So that it can be incident on the side surface.

The probe 100b according to the third embodiment has a structure in which a laser beam incident on the side of the laser incidence part 120 is reflected on the side of the laser incidence part 120 to reflect the laser beam in the direction of the metal nanoparticles 140 And an illumination optical fiber 170 for transmitting external light for imaging when the multiple optical fiber unit 110 to which the laser incidence unit 120 is bonded is used as an imaging probe .

The following describes an endoscope apparatus having a plasmon Raman probe.

First, repetitive descriptions of the same constituent elements are omitted, and the same reference numerals are used for the same constituent elements.

FIG. 9 is a perspective view of a head of an endoscope apparatus having a plasma Raman probe according to the present invention. As shown in FIG. 9, the endoscope head unit 200 includes a plurality of optical fibers 110 receiving a Raman signal, A plasmon Raman probe 100 in which a plurality of metal nanoparticles 140 are attached for excitation and the metal nanoparticles 140 are brought into direct contact with a target tissue; 100, and is configured to output a signal received by the plasmon Raman probe 100 to an external device.

The endoscope apparatus has a monitor system (not shown) for displaying an image photographed by the endoscope head unit 200, as in the known endoscope apparatus, and has a light source for providing white light for illumination.

The endoscope apparatus includes a known Raman spectroscopy system (not shown) connected to the plasma Raman probe unit 100 and capable of detecting and analyzing Raman signals.

The plasmon Raman probe 100 attaches a plurality of metal nanoparticles 140 to the end of the multiple optical fiber unit 110 receiving the Raman signal for plasmon excitation, A laser incidence part 120, a laser guide part 130 and metal nanoparticles 140 so as to be in direct contact with the inspected tissue A of the specimen.

In addition, the plasma Raman probe 100 is installed to be able to draw a certain length from the endoscope head unit 200 so that the attached metal nanoparticles 140 can be directly contacted to the test tissue.

The entire endoscope head part 200 may be brought into contact with the examined tissue, but only the plasmon Raman pro portion 100 is taken out so as to be brought into contact with the examined tissue in order to prevent the vibration information of the examined tissue A from being distorted .

The endoscopic head 200 includes a plurality of optical fibers 110 for receiving the image signal of the measured plasmon Raman probe 100 and a laser guide unit 130 for receiving the Raman signal. To transmit the measured image signal to the monitor system or to control the operation of the Plasmon Raman probe 100 to transmit the measured Raman signal to the Raman spectroscopy system.

That is, when a switching signal for receiving an image signal is input, white light is output, and when a switching signal for receiving the Raman signal is input, the laser beam is output.

In the present embodiment, the plasmon Raman probe 100 performs switching control so that the Raman signal or the image signal of the subject A is selectively received by the endoscope head unit 200 However, the present invention is not limited to this, but may be modified so that switching control may be performed in the endoscope apparatus.

The endoscope head unit 200 includes an air / water channel unit 213 for supplying or removing air and water required for endoscopic photographing, a working channel unit 214 for moving a device for sample collection and treatment of the examinee ). ≪ / RTI >

10, the endoscope apparatus includes an image receiving section 211 for separately receiving an image signal obtained by imaging the subject A on the endoscope head section 200a, a light source section 210 for outputting illumination for measurement of the subject, And an endoscope system 210 including an endoscope 212, an air / water channel 213, a working channel (not shown), and the like.

Therefore, the metal nanoparticles for enhancing the Raman signal are bonded to the probe so that the metal nanoparticles are brought into direct contact with the lesion, thereby preventing the human body from remaining in the material to which the metal nanoparticles are added, and improving the stability.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims. It can be understood that

In the course of the description of the embodiments of the present invention, the thicknesses of the lines and the sizes of the components shown in the drawings may be exaggerated for clarity and convenience of explanation, , Which may vary depending on the intentions or customs of the user, the operator, and the interpretation of such terms should be based on the contents throughout this specification.

100, 100a, 100b: plasmon Raman probe
110: multiple optical fiber part
120: laser incidence part
130: laser guide portion
140: metal nanoparticles
150: Insulator
160:
170: Optical fiber part for illumination
200, 200a: Endoscope head part
210: Endoscope probe
211: image receiver
212:
213: air / water channel section
214: Working channel section

Claims (18)

A plurality of metal nanoparticles 140 for plasmon excitation are provided at the ends of the multiple optical fibers 110 receiving the Raman signal and the metal nanoparticles 140 are formed by locally increasing the electric field Wherein a plasmonic hot spot is generated and the Raman signal is detected when the metal nanoparticles 140 are in direct contact with the examined tissue (A).
The method according to claim 1,
Wherein the probe further comprises a laser guide part (130) for guiding a laser beam to be incident on the metal nanoparticles (140) for amplification of a Raman signal.
3. The method of claim 2,
Wherein a portion of the optical fiber bundles of the multiple optical fibers (110) is connected to a laser beam for generating a Raman signal.
3. The method of claim 2,
Wherein the laser guide unit (130) is separated from an optical fiber bundle of the multiple optical fibers (110) so that a laser beam is incident on a side surface.
5. The method according to any one of claims 2 to 4,
The probe includes a laser incidence part 120 installed between the optical fiber part 110 and the metal nanoparticles 140 and adapted to transmit a laser beam incident from the laser guide part 130 to the metal nanoparticles 140, Further comprising a probe for detecting the plasma.
6. The method of claim 5,
The probe may further include a reflector 160 disposed on at least one side of the laser incidence portion 120 and reflecting the laser beam emitted toward the side of the laser incidence portion 120 toward the metal nanoparticles 140 Wherein the probe is a plasmon probe.
The method according to claim 6,
Wherein the laser incidence part 120 comprises a combination of a GRIN lens or an arbitrary lens for transmitting an image of the subject A to the multiple optical fibers 110.
The method according to claim 6,
Wherein the probe further comprises an illumination optical fiber (170) for outputting illumination light transmitted from the outside for image acquisition of the lesion.
The method according to claim 6,
The metal nanoparticles 140 are characterized in that the distance d2 between the metal nanoparticles 140 is less than the diameter d1 of the metal nanoparticles 140 in order to generate plasmonic hot spots Plasmid Raman probe.
The method according to claim 6,
The metal nanoparticles 140 are formed of any one of silver (Ag), gold (Au), aluminum (Al), copper (Cu), platinum (Pt), and palladium A plasmon Raman probe characterized by.
The method according to claim 6,
Wherein the metal nanoparticles (140) are coated on the periphery of the insulator (150).
12. The method of claim 11,
Wherein the insulator (150) has a thickness of 100 nm or less.
12. The method of claim 11,
Wherein the metal nanoparticles (140) further comprise a Raman indicator material that emits a Raman signal.
As an endoscope apparatus,
A plurality of metal nanoparticles 140 for plasmon excitation are provided at the ends of the multiple optical fibers 110 receiving the Raman signal and the metal nanoparticles 140 are formed by locally increasing the electric field Plasmon Raman probes 100, 100a and 100b configured to generate a plasmonic hot spot and to detect a Raman signal when the metal nanoparticles 140 are in direct contact with the examined tissue A;
A plasmon Raman probe including an endoscope head part 200 or 200a provided with the plasmon Raman probe 100, 100a or 100b and outputting a signal received by the plasmon Raman probe 100, 100a or 100b to an external device, .
15. The method of claim 14,
Wherein the endoscope is configured to perform switching control so that the plasmon Raman probes (100, 100a, 100b) selectively receive any one of a Raman signal or an image signal obtained by measuring the subject's tissue (A) Endoscopic device.
15. The method of claim 14,
Wherein the plasmon Raman probes (100, 100a, 100b) are installed to be able to draw a predetermined length from the endoscope head unit (200, 200a).
17. The method of claim 16,
Wherein the endoscope head part (200) further comprises a working channel part (214) for sampling or treating a sample (A) of the subject's tissue (A).
17. The method of claim 16,
Wherein the endoscope head unit 200a further comprises a light source unit 212 and an image receiving unit 211 for outputting illumination for measurement of the subject A. The endoscope apparatus according to claim 1,

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