KR20210053685A - Multi channel fiber photometry system using adaptive optics - Google Patents

Abstract

Disclosed is a multichannel fiber photometry system using adaptive optics. According to the present invention, the multichannel fiber photometry system using adaptive optics comprises: an excitation light source; one or more optical fiber disposed on an optical path of excitation light generated from the excitation light source, disposed to allow one end to come in contact with a measurement target, and including a discharge light channel through which the excitation light moves to the measurement target and light emitted by the transmitted excitation light are transmitted; an objective lens disposed on the optical path of the excitation light to transmit the excitation light to the optical fiber; a mask adjacent to the objective lens to transmit the excitation light only to the excitation light channel of each optical fiber; a first digital mirror changing the optical path of the excitation light so that the excitation light is transmitted to the measurement target; a first reflection angle adjustment unit setting the reflection angle of the first digital mirror for each predetermined area; and a photographing unit first measuring the discharged light transmitted through the optical fiber. Accordingly, neural activities generated at various locations of the measurement target can be measured easily.

Description

Multi-channel optical fiber photometric system using adaptive optics {MULTI CHANNEL FIBER PHOTOMETRY SYSTEM USING ADAPTIVE OPTICS}

The present invention relates to a technique for measuring neural activity, and more particularly, to a multi-channel optical fiber photometric system using adaptive optics.

The optical fiber photometric method is a type of fluorescence microscope that irradiates excitation light onto a target sample using an optical fiber and receives the excited fluorescence signal again through an optical fiber. So it is being applied to the study of nerve activity.

However, since the conventional optical fiber photometric method measures light intensity using a single optical fiber, there is a limit to simultaneously measuring neural activity that occurs simultaneously and multiple times at several locations.

Unexamined Patent Publication No. 10-2016-0079501 (published date: July 6, 2016)

The present invention has been conceived to solve the above-described problem, and an embodiment of the present invention proposes a multi-channel optical fiber photometric system that performs simultaneous neural activity measurement by mapping an optical fiber to each photometric point of a measurement object. .

In addition, an embodiment of the present invention proposes a multi-channel optical fiber optical intensity measurement system to which a digital mirror capable of adjusting a reflection angle in a fine pixel unit is applied.

A multi-channel optical fiber optical intensity measurement system using adaptive optics according to an embodiment of the present invention for realizing the above object includes an excitation light source; It is disposed on the optical path of the excitation light generated from the excitation light source, disposed so that one end touches the object to be measured, and the excitation light channel through which the excitation light moves to the measurement object and the emission generated by the transmitted excitation light. ) At least one optical fiber comprising an emission optical channel through which light is transmitted; An objective lens disposed on the optical path of the excitation light to transmit the excitation light to the optical fiber; A mask adjacent to the objective lens to allow excitation light to be transmitted only to the excitation optical channel of each of the optical fibers; A first digital mirror that changes the optical path of the excitation light so that the excitation light is transmitted to the measurement object; A first reflection angle adjustment unit for setting a reflection angle of the first digital mirror for each predetermined area; And a photographing unit for first measuring the emitted light transmitted through the optical fiber.

Here, the mask may include holes corresponding to the number of optical fibers, excitation light and emission light move only inside the holes, and fluorescence signals generated around the holes may be removed through the mask.

In some embodiments, a multi-channel optical fiber photometric system using adaptive optics according to an embodiment of the present invention includes: a photo detector for second measuring emitted light transmitted through the optical fiber; A second digital mirror that changes the optical path of the emitted light so that the emitted light enters the photo detector; And a second reflection angle adjustment unit configured to differently set a reflection angle of the second digital mirror for each predetermined area, and transmit only emission light input from a specific optical fiber to the photo detector.

In some embodiments, the multi-channel optical fiber photometric system using adaptive optics according to an embodiment of the present invention further includes a dichroic mirror disposed between the first digital mirror and the objective lens, and the dichroic By a Dichroic mirror, the excitation light is reflected, and the emission light may pass through the Dichroic mirror.

In some embodiments, disposed on the optical path of the emission light, disposed between the photographing unit and the objective lens, the optical path of the emission light is arranged in a first direction toward the photographing unit and a second direction toward the second digital mirror. It may further include a light splitting mirror divided in the direction.

According to the present invention, the following effects occur.

First, neural activity that occurs simultaneously and multiple times at a plurality of points of a measurement object can be simultaneously measured.

Second, using a digital mirror, neuronal activity occurring at multiple points can be independently measured with a single system.

1 is a diagram for conceptually explaining a multi-channel optical fiber optical intensity measurement system using adaptive optics according to an embodiment of the present invention.
2A to 2C are views for explaining a multi-channel optical fiber according to an embodiment of the present invention.
3 shows an image obtained by measuring light intensity in a photographing unit in a multi-channel optical fiber photometric system using adaptive optics according to an embodiment of the present invention.
4 is a diagram illustrating a method of driving a digital mirror according to an embodiment of the present invention.
5 is a block diagram showing the configuration of a multi-channel optical fiber optical intensity measurement system using adaptive optics according to an embodiment of the present invention.
6 shows an implementation example of a multi-channel optical fiber photometric system using the applied optics.

Hereinafter, various embodiments of the present invention will be described in more detail with reference to the accompanying drawings. However, in describing the present invention, when it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the subject matter of the present invention, a detailed description thereof will be omitted.

1 is a diagram for conceptually explaining a multi-channel optical fiber photometric system 1000 using adaptive optics according to an embodiment of the present invention, and a simple “multi-channel optical fiber photometric system 1000 using adaptive optics” Hereinafter, it will be referred to as “photometric system 1000”.

Here, the adaptive optical technology refers to a technology that corrects errors generated in measurement while the optical system changes in real time, the multi-channel optical fiber refers to a bundle of optical fibers including several optical fibers, and the photometric system is a device that measures the intensity of light. Means.

Referring to FIG. 1, the photometric system 1000 irradiates excitation light in a specific wavelength band to a predetermined area of the measurement object TO through an optical fiber, and the emission light generated by the irradiated excitation light Light intensity can be measured.

Here, the excitation light may be generated in a specific wavelength band through the excitation light source, and the emission light may be generated by a fluorescent material disposed on the measurement object TO when the excitation light is irradiated on the measurement object TO.

The photometric system 1000 includes an excitation optical path (EcPa) and an emission optical path (EmPa), and the excitation optical path (EcPa) refers to a path through which excitation light of a specific wavelength is irradiated and transmitted to the measurement target (TO). It means, and the emission light path (EmPa) refers to a path through which emission light, which is a fluorescent signal reacted with excitation light, is transmitted to the measurement object TO. Paths of the excitation light path EcPa and the emission light path EmPa may be changed by a mirror, a lens, a splitter, or the like.

The photometric system 1000 includes a plurality of mirrors (M1, M2), a plurality of lenses (L1, L2, L3), a plurality of filters (EcF, EmF), and a plurality of optical fibers (OF1 to OFN). Digital Mirror (DM1, DM2), Dichroic Mirror (DiM), Beam Splitter (BS), Objective Lens (OL), Mask, Photograph (CA), Photo Detector , PD).

Here, the plurality of digital mirrors DM1 and DM2 may be set to have different reflection angles for each pixel because individual reflection angles can be set up to the pixel unit of the mirror. Pixels mapped to one optical fiber can be grouped and managed. When the digital mirrors DM1 and DM2 are used, the reflection angle of light can be finely adjusted, which is advantageous for system configuration. For example, the photometric system 1000 may be disposed in a narrow space, and fine adjustment of the emission light path EmPa and the excitation light path EcPa may be performed.

The dichroic mirror DiM is disposed between the first digital mirror DM1 and the objective lens OL to selectively transmit or reflect light according to the wavelength of the light. Specifically, the dichroic mirror (DiM) reflects the excitation light and directs it to the objective lens (OL), and in the case of the emitted light, it passes through the first digital mirror (DM1) and goes to the light splitting mirror (BS). You can face it.

The optical splitting mirror BS is disposed on the optical path EmPa of the emitted light, and may be disposed between the photographing unit CA and the objective lens OL, and transmits a beam to the photographing unit CA and the photo detector PD. It can be divided into, and the photographing unit (CA) can measure all the emitted light of the multi-channel optical fiber, but the processing speed may be slightly slower because signal processing must be performed on the emitted light of the multi-channel.

The photo detector PD can measure the emitted light of each of the multi-channel optical fibers, and since the signal processing for the emitted light of each of the multi-channel optical fibers is not performed like the photographing unit CA, the processing speed is fast.

The objective lens OL is disposed on an optical path of excitation light to transmit the excitation light to the optical fiber, and corresponds to a configuration required for a microscope.

In addition, various components of the photometric system 1000 may be arranged so that an image is formed on a plurality of cross-sections AA, BB, CC, and DD.

Hereinafter, a diagram for describing a multi-channel optical fiber with reference to FIGS. 2A to 3. 2A shows a multi-channel optical fiber end 250 according to an embodiment of the present invention, FIG. 2B shows a multi-channel optical fiber bundle 250A according to an embodiment of the present invention, and FIG. 2C shows the multi-channel optical fiber bundle. At 250A, a plurality of channels of an optical fiber when a mask is applied is shown. Each of the channels included in the multi-channel may be mapped to one optical fiber.

The multi-channel optical fiber end 250 in front of the objective lens may include a multi-channel optical fiber bundle 250A, and may include a structure surrounding the multi-channel optical fiber bundle 250A. The multi-channel optical fiber bundle 250A includes a hole representing a plurality of optical fiber channels OF1 to OF7 and an edge bundle OFB constituting a periphery of the hole.

In the case of each hole and channel (OF1 to OF7) connected to the plurality of optical fibers, each of the holes and channels OF7 may have a diameter of 0.4 mm. In addition, the diameter of the border bundle 250A surrounding the optical fiber holes OF1 to OF7 may be 1.3 mm. However, the size may be implemented differently depending on the embodiment. In addition, although it is described that there are seven optical fiber holes OF1 to OF7, the embodiment may be implemented differently depending on the number of optical fibers. The different ends of the multi-channel optical fiber can be separated from each other and placed at various locations on the measurement object.

In addition, the multi-channel optical fiber is disposed on the optical path of the excitation light generated from the excitation light source, and is disposed so that one end touches the measurement target (TO), and the excitation optical channel through which the excitation light moves to the measurement target and the transmitted excitation It may include an emission light channel through which emission light generated by the light is transmitted.

Referring to FIG. 2C, an area (eg, an OFD area) excluding an area in which an optical fiber is disposed in the optical fiber bundle 250A by applying a mask may be excluded and displayed. The mask may be adjacent to the objective lens OL so that the excitation light is transmitted only to the excitation optical channels of the optical fiber.

The mask includes holes corresponding to the number of optical fibers, allows excitation light to move only inside the holes, and fluorescence signals generated around the holes may be removed through the mask. Accordingly, excitation light may be transmitted only to each excitation channel of the optical fiber while noise generated by the OFD region or the like is removed from the excitation light.

3 shows an image obtained by measuring light intensity in a photographing unit in a multi-channel optical fiber photometric system using adaptive optics according to an embodiment of the present invention.

Referring to FIG. 3, a fluorescent signal may be detected only in regions COF1 to COF7 corresponding to an optical fiber in the photographing unit CA, and a fluorescent signal may not be detected in other regions.

The intensity of the light intensity of the regions COF1 to COF7 corresponding to the optical fiber can be measured differently according to the neural activity of the measurement target (TO), and research data can be derived based on this.

4 is a diagram illustrating a method of driving a digital mirror according to an embodiment of the present invention.

In FIG. 4, the left side shows a configuration for adjusting the reflection angle of each pixel (131AA to 131AC, etc.) of the digital mirror, and the right side shows that the reflection angle of the actual digital mirror is adjusted for each pixel.

Both the first digital mirror DM1 and the second digital mirror DM2 may be set to have different reflection angles for each pixel unit and for a predetermined area, and to set the reflection angle for each pixel according to the arrangement of each component. It can be made into a library and used by converting it in real time.

5 is a block diagram showing the configuration of a photometric system 1000 according to an embodiment of the present invention.

Referring to FIG. 5, the photometric system 1000 includes a digital mirror setting unit 100, a photographing unit 200, a photo detector 300, a display 400, an excitation light power supply unit 500, and a storage unit 600. And a control module 700. However, since the components are not essential to implement the photometric system 1000, the photometric system 1000 may be implemented with more or less than the above-described components.

Specifically, the digital mirror setting unit 100 includes first and second digital mirrors 110 and 120 and first and second reflection angle adjustment units 130 and 140 for adjusting the reflection angle of the digital mirror.

The first digital mirror 110 is a digital mirror that reflects excitation light, and the optical path of the excitation light may be set differently for each optical fiber. The first digital mirror 110 may include rows, columns, and pixels, and one optical fiber may correspond to a predetermined number of pixel groups.

Accordingly, when the excitation light is reflected through the first digital mirror 110 by the excitation light source, the reflection angle may be set so that the excitation light is transmitted to each of the plurality of optical fibers. The first reflection angle adjustment unit 130 may adjust the reflection angles of pixels of the first digital mirror 110 so that excitation light can be transmitted to each of the optical fibers in contact with the measurement object TO.

The second digital mirror 120 is a digital mirror that reflects emission light, and reflects only light emitted from a specific optical fiber from the emission light emitted from a plurality of optical fibers and provides it to the photo detector 300.

Specifically, the second reflection angle adjustment unit 140 may set the reflection angle of the second digital mirror 120 differently for each predetermined area, and transmit only the emitted light incoming from a specific optical fiber to the photo detector. The predetermined area may be an area corresponding to each optical fiber.

In this case, the luminous intensity system 1000 performs signal processing on the light emitted from all optical fibers, and uses the photo detector 300 to perform faster luminous intensity measurement than the photographing unit 200 that performs luminous intensity measurement based on the signal processing. You can do it.

The photographing unit 200 may photograph emitted light transmitted from all of the plurality of optical fibers, and may be implemented as a CMOS camera, but embodiments are not limited thereto.

The photographing unit 200 may include an emission light measuring unit 210 to measure light intensity for each optical fiber channel. Based on the measured light intensity, the nerve activity of the object to be measured may be analyzed.

The photo detector 300 measures the luminous intensity of each optical fiber, and thus, the luminous intensity can be measured at high speed. The photo detector 300 may be provided when implementing a wavelength spectrum analyzer, and may perform wavelength spectrum analysis of emitted light.

The display 400 may be used to monitor reflection angles of the first and second digital mirrors, display a result of photometric measurement, and display analyzed neuronal activity information according to photometric measurement.

The excitation light power supply 500 is a module that controls an excitation light source and may allow excitation light of a specific wavelength band to be emitted, and a specific wavelength may be set to 470 nm, but may be implemented differently according to exemplary embodiments.

The storage unit 600 may store reflection angle information for the configured first and second digital mirrors, light intensity measurement information for each measurement object, and the like, and may store various information according to the control of the control module 700.

The control module 700 may set reflection angles of the first and second digital mirrors 110 and 120, and may control overall driving of the photometric system 1000.

6 shows a photometric system 1000A according to an embodiment of the present invention.

Referring to FIG. 6, the photometric system 1000A includes a first digital mirror 110, a second digital mirror 120, a photographing unit 200, a photo detector 300, a beam splitter (BS), and the like. The driving method is described above, and thus will be omitted here.

Here, the configurations of the photometric system 1000A may be arranged as shown in FIG. 6, but the photometric system 1000A may be implemented in a different form in consideration of various environments (space, equipment size, etc.).

Meanwhile, the functional operations and implementations of the subject described in this specification are implemented as digital electronic circuits, or computer software, firmware, or hardware including the structures disclosed in this specification and structural equivalents, or at least one of them. It can be implemented in combination. Implementations of the subject matter described herein are one or more computer program products, i.e., one or more modules relating to computer program instructions encoded on a tangible program storage medium for controlling or executing by the control system. Can be implemented.

On the other hand, the present specification is not intended to limit the present invention to the specific terms presented. Accordingly, although the present invention has been described in detail with reference to the above-described examples, those skilled in the art can make modifications, changes, and modifications to these examples without departing from the scope of the present invention. The scope of the present invention is indicated by the claims to be described later rather than the detailed description, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present invention. do.

Claims (5)

As a multi-channel optical fiber photometric system using adaptive optics,
Excitation light source;
It is disposed on the optical path of the excitation light generated from the excitation light source, disposed so that one end touches the object to be measured, and the excitation light channel through which the excitation light moves to the measurement object and the emission generated by the transmitted excitation light. ) At least one optical fiber comprising an emission optical channel through which light is transmitted;
An objective lens disposed on the optical path of the excitation light to transmit the excitation light to the optical fiber;
A mask adjacent to the objective lens to allow excitation light to be transmitted only to the excitation optical channel of each of the optical fibers;
A first digital mirror that changes the optical path of the excitation light so that the excitation light is transmitted to the measurement object;
A first reflection angle adjustment unit for setting a reflection angle of the first digital mirror for each predetermined area; And
A multi-channel optical fiber photometric system using adaptive optics, comprising a photographing unit for first measuring emission light transmitted through the optical fiber. The method of claim 1,
The mask,
Includes holes corresponding to the number of optical fibers, and excitation light and emission light move only inside the holes,
A multi-channel optical fiber photometric system using adaptive optics in which a fluorescence signal generated around the hole is removed through the mask. The method of claim 1,
A photo detector for measuring a second emission light transmitted through the optical fiber;
A second digital mirror that changes the optical path of the emitted light so that the emitted light enters the photo detector; And
A system for measuring multi-channel optical fiber optical intensity using adaptive optics, further comprising a second reflection angle adjusting unit configured to differently set the reflection angle of the second digital mirror for each predetermined area and transmit only the emitted light incoming from a specific optical fiber to the photo detector. The method of claim 1,
Further comprising a dichroic mirror disposed between the first digital mirror and the objective lens,
By the dichroic mirror,
The excitation light is reflected, and the emission light is transmitted through the dichroic mirror, a multi-channel optical fiber photometric system using adaptive optics. The method of claim 3,
It is disposed on the optical path of the emission light, is disposed between the photographing unit and the objective lens,
A multi-channel optical fiber photometric system using adaptive optics, further comprising a light splitting mirror that divides the light path of the emitted light into a first direction toward the photographing unit and a second direction toward the second digital mirror.

Images