KR101911352B1 - Multi-fluorescence detection device - Google Patents

Abstract

A multi-fluorescence detection device comprises: an LED emitting white light or monochromatic light; an optical probe transferring the white light or the monochromatic light emitted from the LED to a sample and receiving reflected fluorescent emission light from the sample to be transferred; a wide field fluorescence information detection unit detecting the fluorescence emission light transferred from the optical probe; a laser emitting a laser beam; a laser light source unit transferring the laser beam emitted from the laser to the sample through the optical probe; and a laser detection unit detecting the fluorescence emission light reflected from the sample.

Description

[0001] MULTI-FLUORESCENCE DETECTION DEVICE [0002]

The present invention relates to a multi-fluorescence detection apparatus, and more particularly, to a multi-fluorescence detection apparatus capable of diagnosing an endoscope and performing accurate cancer diagnosis in real time without tissue biopsy at a surgical site.

Since 1983, cancer has been the leading cause of death in Korea. In particular, the incidence of cancer is expected to increase as the lifespan of human beings increases due to the improvement of income and medical technology. Especially, It is a well-known fact.

In recent years, the development of an endoscopic microscope system that combines various optical microscopy techniques with conventional endoscopes has become an important issue for more accurate cancer diagnosis. Among them, the clinical usefulness of cancer target disease type fluorescence endoscopy and confocal fluorescence endoscopy have been greatly improved, and the technology development is progressing very rapidly.

However, until now, these techniques have been accompanied by pathological tissue biopsy. Therefore, in order to be used in real-time without endoscopic diagnosis and tissue biopsy at the surgical site, a new concept optical A biopsy technique is needed.

Conventionally, wide field fluorescence molecular imaging endoscopes and confocal fluorescent molecular imaging endoscopic techniques have been disclosed as optical biopsy devices for cancer diagnosis. For example, Korean Patent No. 10-1181395 discloses a confocal fluorescent molecule imaging endoscope technique which can obtain a three-dimensional measurement result even for a specimen whose surface reflectance is not uniform using a plurality of detectors .

However, wide field fluorescence molecular imaging endoscopy has the advantage of wide field of view wide angle and depth of focus, but has difficulty in morphological analysis of cells, while confocal fluorescent molecular imaging endoscope While there was morphological analysis of the cells, there was a problem with narrow field of view and small depth of focus.

Recently, a fusion-type fluorescence molecular imaging endoscopic technique using an optical probe desorption method has been studied which merely has advantages of wide field fluorescence molecular imaging endoscopes and confocal fluorescence molecular imaging endoscopic techniques. However, Diagnosis and surgery.

Therefore, there is a desperate need for a single endoscopic system in which two conventional techniques, that is, a wide field fluorescence molecular imaging endoscope technology and a confocal fluorescence molecular imaging endoscope technology, are implemented.

Korean Patent No. 10-1181395

SUMMARY OF THE INVENTION Accordingly, the present invention has been made in view of the above problems, and it is therefore an object of the present invention to provide a method and apparatus for endoscopic diagnosis and surgical operation by inserting a single optical probe into a biopsy channel of an endoscope, The present invention relates to a multi-fluorescence detection apparatus capable of detecting biochemical fluorescence information based on confocal-based fluorescence information and capable of precise diagnosis of cancer in real time without tissue biopsy based on the obtained detection information.

According to an embodiment of the present invention for realizing the object of the present invention, there is provided a multiple fluorescence detection apparatus comprising: an LED for emitting white light or monochromatic light; a white light or monochromatic light emitted from the LED to a specimen; A wide field fluorescence information detector for detecting the fluorescence emitted from the optical probe, a laser for emitting a laser beam, a laser beam generator for emitting the laser beam emitted from the laser, And a laser detector for detecting the fluorescence emission light reflected from the specimen. The confocal fluorescence information detector includes a laser beam detector for detecting the fluorescence emitted from the specimen, and a laser detector for detecting the fluorescence emitted from the specimen.

In one embodiment, the wide field-of-view fluorescence information detecting section comprises: an objective lens for condensing and irradiating the fluorescence emission light; a first tube lens for condensing the fluorescence emission light emitted from the objective lens; And a CCD (Charge Coupled Device) for measuring the intensity of the fluorescence signal using the emitted fluorescence light and acquiring fluorescence intensity information.

In one embodiment, the laser light source unit includes a collimator lens that converts the laser beam emitted from the laser into parallel light, a laser scanning module that scans the collimated light transmitted through the collimator lens, A scan lens for collecting and transmitting parallel light, and a second tube lens for condensing the parallel light transmitted from the scan lens and irradiating the parallel light to the specimen.

In one embodiment, the apparatus may further include a first optical splitter for switching the path direction of the parallel light to irradiate the parallel light condensed from the second tube lens to the specimen.

The optical scanning device may further include a second optical splitter for switching a path direction of the emitted fluorescence light to transmit the collimated light converted from the collimator lens to the laser scanning module.

In one embodiment, the laser detecting unit reflects the specimen and the path is switched in the first optical splitter to condense the fluorescence emission light sequentially transmitted through the second tube lens, the scan lens, and the laser scanning module A pinhole for receiving the fluorescence emission light, and an optical sensor for acquiring biochemical fluorescence information using the fluorescence emission light that has passed through the pinhole.

In one embodiment, the biochemical fluorescence information may be information comprising at least one of fluorescence lifetime, two photons, multiphoton, Raman.

In one embodiment, the optical probe includes an optical lens unit for converging the fluorescence emission light reflected from the specimen, an optical fiber bundle connected to the optical lens unit and transmitting the fluorescence emission beam forward, And a first optical fiber and a second optical fiber, respectively, disposed at the lower portion.

In one embodiment, the optical probe may further include a case in which the optical lens unit, the optical fiber bundle, and the first and second optical fibers are mounted.

In one embodiment. The white light or the monochromatic light emitted from the LED is irradiated to the specimen via the first optical fiber and the second optical fiber and the laser beam emitted from the laser is irradiated onto the specimen via the optical fiber bundle .

According to these embodiments, cancer diagnosis can be performed in real time without endoscopic diagnosis and tissue biopsy at the surgical site.

In addition, fluorescent molecule imaging of target disease and confocal-based fluorescence molecule imaging functions can be performed simultaneously in a single channel.

In addition, the photoprobe uses two independent light source channels for effective fluorescence detection of target disease and confocal, and uses fluorescence information of the target disease by a wide field light source and fluorescence information by a confocal light source Biochemical fluorescence information can be stored and diagnosed in separate multiplexed fluorescence detection devices via a single channel.

In addition, based on the fluorescence intensity information of the light field, a single light probe capable of performing two functional functions based on the target disease and the confocal focusing is used to proceed with the primary cancer, and fluorescence intensity information of the confirmed cancer biochemical Secondary cancer analysis and diagnosis based on fluorescence information can improve the accuracy of cancer diagnosis and also it is possible to carry out second infection and time saving due to bleeding because cancer biopsy is unnecessary.

1 is a perspective view illustrating a multiple fluorescence detection apparatus according to an embodiment of the present invention.
FIG. 2A is a schematic diagram showing a light path of fluorescence emission light when white light or monochromatic light is irradiated on a specimen in the multiple fluorescence detection apparatus of FIG. 1; FIG.
FIG. 2B is a schematic diagram showing a light path of fluorescence emission light when a laser beam is irradiated on a specimen in the multiple fluorescence detecting apparatus of FIG. 1; FIG.

While the present invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not limited to the disclosed embodiments. It is to be understood, however, that the invention is not intended to be limited to the particular forms disclosed, but on the contrary, is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. Like reference numerals are used for like elements in describing each drawing. The terms first, second, etc. may be used to describe various elements, but the elements should not be limited by the terms. The terms are intended to distinguish one element from another Only. The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In the present application, the term "comprises" or "comprising ", etc. is intended to specify that there is a stated feature, figure, step, operation, component, But do not preclude the presence or addition of one or more other features, integers, steps, operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

1 is a perspective view illustrating a multiple fluorescence detection apparatus according to an embodiment of the present invention.

Referring to FIG. 1, the multi-fluorescence detecting apparatus 1 according to the present embodiment includes an LED 10, an optical probe 100, a wide field fluorescence information detecting unit 200, a laser 20, And a confocal fluorescence information detector 300.

The monochromatic light or the white light is incident on the optical probe 100 through the illumination optical fiber 101. The monochromatic light or the white light is incident on the optical probe 100 through the optical fiber 101 for illumination, Passes through the optical probe 100 and enters the specimen 30 containing the fluorescent material, that is, the specimen.

The optical probe 100 transmits the white light or the monochromatic light emitted from the LED 10 to the specimen 30 and receives and transmits the fluorescence emission light reflected from the specimen 30.

The wide field fluorescence information detecting unit 200 detects the fluorescence emitted from the optical probe 100 and includes an objective lens 210, a first first tube lens 220, And a charge coupled device (CCD) 230.

The wide-field fluorescence information detecting unit 200 detects the fluorescence emitted from the sample using the fluorescence emission light, and transmits the monochromatic light or the white light to the specimen. The fluorescence image of the light source 30 can be obtained.

The objective lens 210 collects and emits the fluorescence emission light emitted via the optical probe 100. The objective lens 210 may be a single lens, or may be an objective lens module in which various kinds of objective lenses can be arranged in a predetermined position.

An objective lens having NA equal to that of the optical probe 100 may be used in order to prevent the loss of fluorescence emission light from passing through the optical probe 100.

The first tube lens 220 collects the fluorescence emitted from the objective lens 210 to form a fluorescent image, and transmits the fluorescence emitted light to the CCD 230.

The CCD 230 is an image sensor, and can output the fluorescence image generated by the first tube lens 220 to monitor the fluorescence image.

Also, the CCD 230 measures the intensity of the fluorescence signal using the fluorescence emission light and acquires fluorescence intensity information for a specific position of the specimen 30. At this time, the fluorescence intensity information is wide field fluorescence information, and it is possible to confirm and diagnose the presence or absence of cancer of the specimen from the specimen.

Further, the CCD 230 may measure an image in a conjugate focal plane of the objective lens 210, and may acquire a fluorescence image of the specimen 30 through the intensity of the fluorescence signal. have.

The laser 20 emits a laser beam of various wavelengths.

The confocal fluorescence information detection unit 300 includes a laser light source unit 301 and a laser detection unit 302 for scanning the laser beam emitted from the laser 20 in a confocal manner.

The laser light source unit 301 transmits the laser beam emitted from the laser 20 to the specimen 30 through the optical probe 100. The collimator lens 310 and the laser scanning module 320 A scan lens 330, and a second tube lens 340.

The laser beam emitted from the laser 20 is converted into parallel light by the collimator lens 310. Thereafter, the path direction is switched by the second optical splitter 500 and scanned by the laser scanning module 320.

The parallel light scanned by the laser scanning module 20 is sequentially transmitted through the scan lens 330 and the second tube lens 340 and is scanned by the specimen 30.

More specifically, the scan lens 330 condenses the collimated light transmitted from the laser scanning module 330, and the second tube lens 340 collimates the collimated light transmitted through the scan lens 330 Concentrate and inject.

Thereafter, the parallel light is changed in the path direction by the first optical splitter 400 and transmitted to the objective lens 210, and the objective lens 210 condenses the parallel light onto the specimen 30 Investigate.

The first and second optical distributors 400 and 500 guide the direction of light so that light can be provided from the laser 20 toward the specimen 30, And guide the light in various positions or angles according to the relative positions of the laser scanning module 320 and the specimen 30. [

Furthermore, the optical distributors 400 and 500 may be additionally disposed in addition to the two illustrated, and the arrangement positions may be variously changed.

The laser detector 302 detects the fluorescence emitted from the specimen 30 and includes a condenser lens 350, a pinhole 360, and an optical sensor 370.

Here, the parallel emission light is incident on the specimen 30 and is then emitted with loss of energy. The laser detection unit 302 detects the fluorescence image of the specimen 30 using the fluorescence emission light, Can be obtained.

The fluorescence emitted from the sample 30 is transmitted through the optical probe 100 to the second tube lens 340 by the first optical splitter 400. The fluorescence emission light transmitted to the second tube lens 340 sequentially passes through the scan lens 330 and the laser scanning module 320.

Then, the fluorescence emission light is transmitted to the condensing lens 350, and the condensing lens 350 condenses the fluorescence emission light and irradiates the pinhole 360. The fluorescence emission light is incident on the pinhole 360 and then converged to the optical sensor 370.

The optical sensor 370 can acquire biochemical fluorescence information including fluorescence lifetime, two-photon, multiphoton, and Raman using the fluorescence emission light.

The biochemical fluorescence information may be confocal fluorescence information, and the presence or absence of primary cancer in the fluorescence intensity information may be diagnosed, and secondary cancer analysis and diagnosis may be performed based on the biochemical information. Thus, the accuracy of cancer diagnosis can be further improved, and time can be saved because cancer tissue biopsy is unnecessary.

FIG. 2A is a schematic diagram showing a light path of fluorescence emission light when white light or monochromatic light is irradiated on a specimen in the multiple fluorescence detection apparatus of FIG. 1; FIG.

FIG. 2B is a schematic diagram showing a light path of fluorescence emission light when a laser beam is irradiated on a specimen in the multiple fluorescence detecting apparatus of FIG. 1; FIG.

2A, the optical probe 100 includes an optical lens unit 110, an optical fiber bundle 120, a first optical fiber 130, a second optical fiber 140, and a case 150 .

The optical lens unit 110 is disposed at one end of the optical probe 100 and serves to converge the fluorescence emitted from the specimen.

The optical fiber bundle 120 is formed as a bundle of a plurality of optical fibers and is connected to one end of the optical lens unit 110 and extended. Therefore, the fluorescence emission light having passed through the optical lens unit 110 can be straightened along the longitudinal direction of the optical fiber bundle 120.

Here, the optical fiber is a fiber made by elongating a transparent dielectric such as quartz glass or plastic, and has a diameter of usually 0.1 to 1 mm. The optical fiber is centered on a medium having a high refractive index and the periphery is covered with a medium having a low refractive index. Specifically, the central core portion and the surrounding cladding portion have a double cylindrical shape, and the outside is coated with the synthetic resin coating one or two times in order to protect it from impact.

The principle of optical fiber is the principle of total reflection. For example, when the angle of incidence of light at the interface between two transparent materials having different refractive indexes is matched with the condition, the phenomenon of full reflection of light occurs. Specifically, when the light passes through the optical fiber, the cladding acts as a mirror to reflect light. The reflected light then passes through the core again and is then reflected back to the cladding. This process is repeated so that light is transmitted through the optical fiber. Therefore, only the reflection occurs at the interface between the core and the cladding, and no refraction occurs. Thus, the light can be emitted to the end of the optical fiber without emitting light.

The first optical fiber 130 and the second optical fiber 140 are formed on the upper and lower portions of the optical fiber bundle 120, respectively. The first and second optical fibers 130 and 140 may be formed of the same material as the optical fiber bundle 120 described above.

The case 150 is formed of a flexible material in which the optical lens unit 110, the optical fiber bundle 120, and the first and second optical fibers 130 and 140 are mounted. The case 150 may further include an adjusting unit (not shown) for adjusting the position of the optical fiber bundle 120 and the first and second optical fibers 130 and 140.

2A, the white light or the monochromatic light emitted from the LED 10 is incident on the specimen 30 through the first and second optical fibers 130 and 140 in a large area, . Also, the fluorescence emission light reflected by the specimen 30 has a long depth of focus and is converged by the optical lens unit 110 and passes through the optical fiber bundle 120.

2B, the laser beam emitted from the laser 20 is incident on the specimen 30 through the optical fiber bundle 120 at a narrow area, thereby exhibiting a narrow visual field area.

In this case, the laser beam may be converged in the longitudinal direction of the optical fiber bundle 120 and may be irradiated to the central portion of the specimen 30 through the optical lens unit 110, .

When the laser beam is irradiated to the central portion of the specimen 30, the fluorescence emission light reflected by the specimen 30 passes through the axis of the optical fiber bundle 120, and the laser beam passes through the axis of the specimen 30 When irradiated onto a region other than the center portion, the fluorescence emission light reflected by the specimen 30 passes through a region other than the axis of the optical fiber bundle 120.

According to the embodiments of the present invention, cancer diagnosis can be performed in real time without endoscopic diagnosis and tissue biopsy at the surgical site.

In addition, fluorescent molecule imaging of target disease and confocal-based fluorescence molecule imaging functions can be performed simultaneously in a single channel.

In addition, the photoprobe uses two independent light source channels for effective fluorescence detection of target disease and confocal, and uses fluorescence information of the target disease by a wide field light source and fluorescence information by a confocal light source Biochemical fluorescence information can be stored and diagnosed in separate multiplexed fluorescence detection devices via a single channel.

In addition, based on the fluorescence intensity information of the light field, a single light probe capable of performing two functional functions based on the target disease and the confocal focusing is used to proceed with the primary cancer, and fluorescence intensity information of the confirmed cancer biochemical Secondary cancer analysis and diagnosis based on fluorescence information can improve the accuracy of cancer diagnosis and also it is possible to carry out second infection and time saving due to bleeding because cancer biopsy is unnecessary.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention as defined by the following claims. It can be understood that it is possible.

10: LED 20: laser
100: optical probe 110: optical lens part
120: optical fiber bundle 130: first optical fiber
140: second optical fiber 150: case
200: wide-angle type fluorescence information detection unit 210: objective lens
220: first tube lens 230: CCD
300: incident light type fluorescence information detection unit 301: laser light source unit
302: LASER DETECTOR 310: COLUMNER LENS
320: laser scanning module 330: scan lens
340: second tube lens 350: condenser lens
360: Pinhole 370: Light sensor
400: first optical splitter 500: second optical splitter

Claims (10)

An LED for emitting white light or monochromatic light;
An optical lens unit that transmits the white light or the monochromatic light emitted from the LED to a specimen, receives and transmits fluorescence emission light reflected from the specimen, and converges the fluorescence emission light reflected from the specimen; And a first optical fiber and a second optical fiber disposed at upper and lower portions of the optical fiber bundle, the optical fiber bundle being connected to the optical fiber bundle and transmitting the fluorescence emission light in the longitudinal direction;
A wide field fluorescent light (hereinafter referred to as " wide field fluorescent light ") including a CCD (Charge Coupled Device) for measuring the intensity of a fluorescent signal using the fluorescence emitted from the optical probe and obtaining fluorescence intensity information for a specific position of the specimen An information detector;
A laser emitting a laser beam; And
A laser light source unit that transmits the laser beam emitted from the laser to the specimen through the optical probe; and a biochemical system including at least one of a fluorescence lifetime, a two-photon, a multiphoton, and Raman using the fluorescence emission light reflected from the specimen. And a confocal fluorescence information detecting unit including a laser detecting unit including an optical sensor for obtaining red fluorescence information,
Wherein the white light or the monochromatic light emitted from the LED is irradiated to the specimen via the first optical fiber and the second optical fiber, the fluorescence emission light reflected from the specimen is converged to the optical lens unit, passes through the optical fiber bundle,
Wherein the laser beam emitted from the laser beam is irradiated to a central portion of the specimen via the optical fiber bundle and the fluorescence emission light reflected at the center portion of the specimen passes through the axis of the optical fiber bundle. Device. The apparatus according to claim 1, wherein the wide-
An objective lens for condensing and irradiating the fluorescence emission light; And
And a first tube lens for condensing the fluorescence emission light emitted from the objective lens. The laser light source unit according to claim 1,
A collimator lens for converting the laser beam emitted from the laser into parallel light;
A laser scanning module for scanning the collimated light transmitted through the collimator lens;
A scan lens for condensing and transmitting the parallel light transmitted from the laser scanning module; And
And a second tube lens for condensing the parallel light transmitted from the scan lens and irradiating the specimen with the parallel light. The method of claim 3,
Further comprising: a first optical splitter for switching the path direction of the parallel light to irradiate the parallel light condensed from the second tube lens to the specimen. The method of claim 3,
Further comprising a second optical splitter for switching a path direction of the fluorescence emission light to transmit the parallel light converted from the collimator lens to the laser scanning module. 5. The apparatus according to claim 4,
A converging lens for converging and irradiating the fluorescence emitted from the second tube lens, the scan lens, and the laser scanning module sequentially, the path being switched by the first optical splitter; And
And a pinhole for receiving the fluorescence emission light. delete delete The optical scanning device according to claim 1,
Further comprising a case in which the optical lens unit, the optical fiber bundle, and the first and second optical fibers are mounted. delete

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