JP6255559B2 - Biological light image acquisition system, biological light acquisition probe, and biological light image acquisition method - Google Patents

Description

  The present invention relates to a system for acquiring a biological light image indicating a state of biological light emitted from a specimen portion of an object to be inspected, a biological light acquisition probe used for the system, and a method for acquiring a biological light image using the system About.

  Conventionally, in biochemical analysis or the like, a method in which a luminescent material treated so as to bind to a detection target cell or the like is administered to a living body, and light emitted from the luminescent material is observed from outside the living body may be used. . Examples of such a luminescence phenomenon include spontaneous luminescence such as fireflies and chemiluminescence caused by luciferase. Chemiluminescence is caused by an enzyme reaction with a substrate, and is widely used for ATP (adenosine triphosphate) measurement, gene biochemical analysis, blood stain inspection, and the like. The state of light emission is acquired as a two-dimensional image by an imaging device including a lens and a camera (see, for example, Patent Document 1).

  As a method for observing a minute region of a living body, there is a micro imaging method using an optical fiber. In this method, an imaging fiber in which a plurality of optical fibers are bundled is inserted into a living body, and the state of the living body is observed (for example, see Patent Document 2).

JP 2003-15981 A JP 2000-81587 A

  In the method described in Patent Literature 1, since light emitted from a living body is captured by a general video camera, it is difficult to capture biological light emitted from a minute region of the living body. In addition, the method using a conventional objective lens for observing biological light in the deep part of the living body is highly invasive and has a large deviation from the normal state of the living body. Therefore, when trying to capture biological light emitted from a minute region in the living body using the apparatus of Patent Document 2, biological light with weak light intensity is buried in background light with high light intensity. It is difficult to acquire an image that captures biological light.

  Therefore, the present invention provides a biological light image acquisition system, a biological light acquisition probe, and a biological light image acquisition method that can acquire a biological light image that captures biological light emitted from a specimen portion of a subject.

  One aspect of the present invention is a system for acquiring a biological light image indicating a state of biological light emitted from a specimen portion of an object to be inspected, a dark box that houses the object to be inspected and forms a light shielding space, and a plurality of lights An optical waveguide for guiding biological light incident on the tip of the optical fiber to the other end of the optical fiber, and a light shielding layer provided so as to cover a side surface of the optical waveguide; A biological light acquisition probe disposed in a dark box, and an image acquisition device that receives a biological light emitted from the other end and acquires a biological light image using the biological light, The light shielding layer has a light shielding wall portion that protrudes from the light incident surface including the tip portions of the plurality of optical fibers and is formed so as to surround the light incident surface.

According to this biological light image acquisition system, biological light incident from the light incident surface of the biological light acquisition probe is incident on the image acquisition device, and a biological light image indicating the state of biological light is acquired.
Here, the light that can be background light in the biological light image includes ambient light in the environment where the object to be inspected is arranged. In this biological light image acquisition system, the object to be inspected is in a dark box that forms a light shielding space. Because it is housed, the influence of ambient light is eliminated.
In addition, light may be generated in a place other than the specimen part to be inspected in the object to be inspected, and if this light emission is guided to the image acquisition device through the optical waveguide part, it can become background light in the biological light image. According to this biological optical image acquisition system, since the light shielding layer is provided so as to cover the side surface of the optical waveguide unit, the incidence of light emission from the side surface of the optical waveguide unit is suppressed. Furthermore, a light shielding wall is formed in the light shielding layer on the distal end side of the biological light acquisition probe. Since this light shielding wall portion is formed so as to protrude from the light incident surface including the tip portions of the plurality of optical fibers and surround the light incident surface, the light shielding wall portion is generated at a place other than the sample portion facing the light incident surface. Incident light on the light incident surface is suppressed.

  Accordingly, since light that can be background light is prevented from being incident on the image acquisition device, a living body having a good S / N ratio is not buried in background light having a high light intensity without being buried with a weak biological light. An optical image can be acquired.

  Further, the dark box has a light absorption part arranged in the light shielding space, and the object to be inspected is arranged in the light absorption part. According to such a structure, since background light is further reduced, a biological light image having a better S / N ratio can be acquired.

  Moreover, the image acquisition apparatus has a light input unit into which biological light is incident, and the light input unit is disposed in a dark box. Since the space between the other end of the biological light acquisition probe and the light input part of the image acquisition device is arranged in the light-shielding space in the dark box, the background light is further reduced, so that a biological optical image having a better S / N ratio can be obtained. Can be acquired.

  The angle between the light incident surface of the optical waveguide section and the optical axis direction of the optical fiber is 0 degree or more and less than 90 degrees. According to such a structure, the biological light acquisition probe can easily enter the living body.

  Further, according to another aspect of the present invention, in a biological light acquisition probe that acquires biological light emitted from a specimen portion of an object to be inspected, a plurality of optical fibers are bundled in a radial direction and are incident on a distal end portion of the optical fiber. An optical waveguide that guides biological light to the other end of the optical fiber, and a light shielding layer that covers the side surface of the optical waveguide, and the optical waveguide includes the tips of a plurality of optical fibers. The light-shielding layer has a light-shielding wall portion that protrudes from the light-incident surface and that surrounds the light-incident surface.

  According to this biological light acquisition probe, since the light shielding layer is provided so as to cover the side surface of the optical waveguide unit, the incidence of light emission from the side surface of the optical waveguide unit is suppressed. Furthermore, a light shielding wall is formed in the light shielding layer on the distal end side of the biological light acquisition probe. Since this light shielding wall portion is formed so as to protrude from the light incident surface including the tip portions of the plurality of optical fibers and surround the light incident surface, the light shielding wall portion is generated at a place other than the sample portion facing the light incident surface. Incident light on the light incident surface is suppressed. Accordingly, since light that can be background light is prevented from entering the optical waveguide section, a living body having a good S / N ratio is not buried in background light having a high light intensity without being buried with a weak biological light. An optical image can be acquired.

  According to another aspect of the present invention, there is provided a biological light image acquisition method for acquiring a biological light image indicating a state of biological light radiated from a specimen portion of the inspection object, and forming a light shielding space in the inspection object. An image acquisition device for receiving biological light emitted from the biological light acquisition probe; and a step of bringing the tip of the light shielding wall portion of the light shielding layer of the biological light acquisition probe into contact with the specimen portion. A biological light acquisition probe, wherein the biological light acquisition probe includes a plurality of optical fibers bundled in a radial direction, and the biological light incident on the distal end portion of the optical fiber is transmitted to the other end portion of the optical fiber. An optical waveguide for guiding, and a light shielding layer provided so as to cover a side surface of the optical waveguide, and the light shielding wall protrudes from a light incident surface including tips of a plurality of optical fibers. It is formed so as to surround the light incident surface.

  According to this biological light image acquisition method, the biological light incident from the light incident surface of the biological light acquisition probe is incident on the image acquisition device, and the biological light image indicating the state of the biological light is acquired. In this biological light image acquisition system, since the object to be inspected is housed in a dark box that forms a light-shielding space, the influence of ambient light is eliminated. Moreover, since the light shielding layer is provided so as to cover the side surface of the optical waveguide unit, the incidence of light emission from the side surface of the optical waveguide unit is suppressed. Furthermore, a light shielding wall is formed in the light shielding layer on the distal end side of the biological light acquisition probe. The light shielding wall portion protrudes from the light incident surface including the tip portions of the plurality of optical fibers and is formed so as to surround the light incident surface, and since the light shielding wall portion is in contact with the sample portion, Incidence of light generated at a place other than the specimen portion facing the incident surface to the light incident surface is suppressed. Accordingly, since light that can be background light is prevented from being incident on the image acquisition device, a living body having a good S / N ratio is not buried in background light having a high light intensity without being buried with a weak biological light. An optical image can be acquired.

  In addition, the optical waveguide part may be attached to and integrated with the light shielding layer, and the optical waveguide part and the light shielding layer may be simultaneously inserted into the object to be inspected in the step of contacting the specimen part. The optical waveguide is separate from the light shielding layer, and in the step of contacting the specimen portion, the light shielding layer is inserted into the object to be inspected and after the step of contacting the specimen portion, a biological light image is acquired. Prior to the step, the optical waveguide part may be inserted into the light shielding layer so that the light shielding wall part protrudes from the light incident surface.

  ADVANTAGE OF THE INVENTION According to this invention, the biological light image which caught the biological light radiated | emitted from the sample part of the to-be-inspected object can be acquired.

It is the schematic which shows the structure of the biological optical image acquisition system which concerns on this invention. It is sectional drawing which shows the front-end | tip structure of the biological light acquisition probe shown by FIG. It is sectional drawing which shows the modification of the biological light acquisition probe which concerns on this invention. It is sectional drawing which shows the modification of the biological light acquisition probe which concerns on this invention. It is sectional drawing which shows the modification of the biological light acquisition probe which concerns on this invention. It is the background light image acquired with the biological light image acquisition system which concerns on a comparative example, and the background light image acquired with the biological light image acquisition system which concerns on this invention. It is a biological light image acquired with the biological light image acquisition system which concerns on this invention.

  DESCRIPTION OF EMBODIMENTS Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the accompanying drawings. In the description of the drawings, the same elements are denoted by the same reference numerals, and redundant description is omitted.

  As shown in FIG. 1, the biological light image acquisition system 1 is a system that acquires a biological light image indicating the state of biological light emitted from the specimen portion 2 a in the subject 2. The subject 2 is administered with a drug that binds to the detection target cell and emits light through a chemical reaction. The biological light image acquisition system 1 detects the intensity of light emitted from the specimen portion 2a to which the drug is bonded and the two-dimensional distribution of light, and records them in an image.

  The biological light image acquisition system 1 uses a dark box 3 that forms a light-shielding space 3 a, a biological light acquisition probe 4 that acquires biological light from the specimen 2 a, and biological light acquired by the biological light acquisition probe 4. And an image acquisition device 6 that forms an optical image.

  The dark box 3 forms a light shielding space 3a having a size capable of accommodating the object 2 to be inspected. Inside the dark box 3, a light absorption box (light absorption part) 7 made of a porous material or styrene foam is arranged, and the device under test 2 is arranged in the light absorption box 7. The dark box 3 preferably has a size that covers from the tip of the biological light acquisition probe 4 to the light input unit (lens) 6a of the image acquisition device 6.

  As shown in FIG. 2, the biological light acquisition probe 4 acquires biological light emitted from the specimen portion 2 a by being in contact with the specimen portion 2 a on or inside the test object 2. The biological light acquisition probe 4 includes an optical waveguide 9 that guides biological light incident on the tip 8a (see FIG. 1) of the optical fiber 8 to the other end 8b (see FIG. 1) of the optical fiber 8, and an optical waveguide. And a light shielding layer 11 provided so as to cover the side surface 9a of the portion 9.

  The optical waveguide 9 is a so-called imaging fiber in which a plurality of optical fibers 8 having a fiber diameter of several micrometers are bundled in the radial direction, and has a low invasiveness of 5 mm or less in diameter like an injection needle. In this embodiment, the wavelength band of the biological light to be detected is 300 nm to 2000 nm including ultraviolet rays, visible rays, and infrared rays. In order to efficiently guide biological light in such a wavelength band, the optical waveguide unit 9 is configured using a material such as purified quartz, synthetic quartz, or high-performance plastic. A light incident surface 9b that includes the tip 8a of the optical fiber 8 and is in close contact with the specimen 2a is formed on the tip of the optical waveguide 9. The light incident surface 9b is inclined with respect to the optical axis direction of the optical fiber 8 and has a sharp structure with respect to the inspected object 2 in combination with the light shielding wall portion 11a. The angle between the light incident surface 9b and the optical axis direction of the optical fiber 8 may be set to an angle of not less than 0 degrees and less than 90 degrees (for example, about 10 degrees) according to the object 2 to be inspected. According to the appropriately set angle, the biological light acquisition probe 4 can be easily inserted into the subject 2 such as an organ or a biological tissue.

  The light shielding layer 11 provided in the optical waveguide 9 suppresses intrusion of light that can be background light from the periphery of the side surface 9 a and the light incident surface 9 b of the optical waveguide 9. The light shielding layer 11 shields light having a wavelength band of 300 nm to 2000 nm to be detected. The light shielding layer 11 is in close contact with the optical waveguide portion 9, and the optical waveguide portion 9 and the light shielding layer 11 are integrated. The light shielding layer 11 is separated from the optical waveguide 9 without being in close contact, and the optical waveguide 9 is inserted into the light shielding layer 11 after the light shielding layer 11 is inserted into the device under test 2 at the time of inspection. The structure inserted may be sufficient. In the case of the close contact structure, for example, the periphery of the optical waveguide 9 and the light incident surface 9b is covered with a material including vinyl, resin, plastic, or a light absorbing material. In the case of a non-contact structure, the optical waveguide 9 is inserted into a light shielding tube made of hard stainless steel, plastic, soft vinyl tube or the like. Further, the tip of the light shielding tube may be formed so as to be orthogonal or oblique to the optical axis of the optical fiber 8, and may be matched to the tip shape of the optical waveguide section 9.

  A light shielding wall portion 11 a serving as a guide wall is formed on the tip side of the light shielding layer 11. The light shielding wall portion 11a surrounds the light incident surface 9b and shields the intrusion of light that becomes a disturbance from the periphery of the sample portion 2a that is in close contact with the light incident surface 9b. The light shielding wall portion 11a is formed so as to protrude from the light incident surface 9b including the tip portions 8a of the plurality of optical fibers 8 and to surround the light incident surface 9b in the circumferential direction.

  In the above-described biological light acquisition probe 4, for example, a bundle fiber forming the optical waveguide 9 is inserted into a hard stainless steel light-shielding tube whose tip is formed obliquely in advance. And a bundle fiber is grind | polished so that the front-end | tip shape of a light shielding tube may be followed, and after completion | finish of grinding | polishing, resin is filled between a bundle fiber and a light shielding tube, and the position of a bundle fiber is fixed. In some cases, the light shielding tube that forms the light shielding layer 11 and the bundle fiber that forms the optical waveguide unit 9 are not connected, but are applied to the living body (inspected object 2) in a separate order. When the light shielding tube is a soft vinyl light shielding tube, the bundle fiber inserted into the stainless steel tube and whose tip is polished obliquely is transferred to the soft vinyl light shielding tube. Resin is filled between vinyl shading tubes to fix the position of the bundle fiber.

  According to the living body light acquisition probe 4 having such an optical waveguide section 9 and the light shielding layer 11, the light incident surface 9b can be brought into close contact with the surface of the living body or the sample section 2a in the living body, and further into the living body. Can be inserted easily. In addition, background light due to light leakage from the periphery of the specimen portion 2 a can be removed, and biological light having a high S / N ratio can be emitted to the image acquisition device 6. And light-shielding property can be improved, without changing the size of optical fiber 8 itself which comprises the optical waveguide part 9 largely. Therefore, the dark box 3 for covering the object to be inspected 2 and the biological light acquisition probe 4 and the like can use a conventional product, and easy position control can be expected.

  As shown in FIG. 1, the image acquisition device 6 has high sensitivity capable of detecting biological light by chemiluminescence whose light intensity is orders of magnitude lower than fluorescence (for example, about 1/100 to 1/10000). A two-dimensional image is formed using biological light. Further, the image acquisition device 6 may have a wide dynamic range capable of detecting fluorescence having light intensity larger than that of biological light generated by chemiluminescence, in addition to biological light generated by chemiluminescence. The image acquisition device 6 may be connected to a cooling device 12 for suppressing a decrease in the S / N ratio due to thermal noise.

  In addition to the dark box 3, the biological light acquisition probe 4, and the image acquisition device 6, the biological light image acquisition system 1 further includes a manipulator 13 for moving the biological light acquisition probe 4, and the biological light acquisition probe 4. The X-ray camera 14 for confirming the tip position, the optical system 16 disposed on the optical path between the biological light acquisition probe 4 and the image acquisition device 6, the image acquisition device 6 and the manipulator 13, and the biological body are controlled. And a processing control unit 17 for processing the optical image.

  The manipulator 13 is a mechanism that moves the biological light acquisition probe 4 disposed in the dark box 3 to a predetermined position, and can manually or automatically operate the tip position of the biological light acquisition probe 4 from the outside of the dark box 3. . The manipulator 13 may be provided with an illuminated camera system 13a for confirming the relative position of the device under test 2 and the biological light acquisition probe 4.

  Before the tip of the biological light acquisition probe 4 enters the object to be inspected 2, the tip position and image can be confirmed by the illuminated camera system 13 a provided in the manipulator 13. Bright field images can be taken with illumination light, and long-wavelength light can be used to reach deep objects. When the illumination is extended from the camera system, for example, there is a mode in which an illumination body is attached to the outer periphery of the biological light acquisition probe to illuminate from the tip. Or after making the front-end | tip of the biological light acquisition probe 4 penetrate | invade into the to-be-inspected object 2, it is difficult to confirm the position of a front-end | tip correctly with the camera system 13a with illumination. Therefore, the biological optical image acquisition system 1 may include an X-ray camera 14 disposed outside the dark box 3. The dark box 3 is formed of a material that can transmit X-rays, and the light shielding layer 11 of the biological light acquisition probe 4 is formed of a metal material that shields X-rays, whereby the biological light acquisition probe 4 in the inspection object 2 is formed. It is possible to accurately confirm the tip position of the.

  An optical system 16 is disposed on the optical path between the other end 8 b of the biological light acquisition probe 4 and the light input unit 6 a of the image acquisition device 6. The optical system 16 is disposed on the biological light acquisition probe 4 side, and is disposed on the image acquisition device 6 side with the lens 16a having a light condensing property close to the other end portion 8b of the biological light acquisition probe 4. The lens 16b used for image formation is provided. Further, the optical system 16 includes a light source for irradiating the specimen portion 2a, a mirror or beam splitter for changing the direction of the optical path, and a wavelength selection filter for selecting light of a specific wavelength, as necessary. May be. By having these configurations, it is possible to acquire a biological light image capturing chemiluminescence and an image capturing fluorescence.

  The processing control unit 17 is connected to the image acquisition device 6, controls the operation of the image acquisition device 6, and processes and displays the biological light image input from the image acquisition device 6. The processing control unit 17 can use a personal computer 17a or an input / output device 17b.

  Next, a biological light image acquisition method using the above-described biological light image acquisition system 1 will be described.

  First, a test object 2 is prepared, and a drug having a luminescent property and an action of binding to a cell tissue to be detected is administered to the test object 2. For example, when the substrate luciferin is administered, the phenomenon that the luciferase enzyme oxidizes luciferin with the energy of ATP and oxyluciferin emits light can be utilized. In addition, cell tissues to be detected include, for example, fragile tissues such as brain, pancreas, spinal cord, testis, submandibular gland, etc. In order to emit a luminescent signal in such cell tissues, for example, a luciferase enzyme is encoded. A gene is injected into a fertilized egg of a mouse to produce a transgenic mouse, which is to be inspected 2. When a substrate luciferin is administered to a tissue expressing a luciferase enzyme, a luminescence signal can be emitted. Then, the dark box 3 is opened, and the device under test 2 is placed in the light absorption box 7 of the dark box 3.

  Subsequently, the position of the specimen portion 2a in the inspection object 2 is determined, and the tip of the biological light acquisition probe 4 is manually or automatically placed near the inspection object 2 while checking the image of the illuminated camera system 13a of the manipulator 13. Move with. Then, as shown in FIG. 2, the biological light acquisition probe 4 is inserted into the inspection object 2 so that the tip of the biological light acquisition probe 4 is in close contact with the specimen portion 2 a set inside the inspection object 2. To do. More specifically, in the method for acquiring a biological light image according to the present embodiment, the tip of the light shielding wall portion 11a of the biological light acquisition probe 4 and the light incident surface 9b are brought into close contact with the sample portion 2a. When the optical waveguide 9 and the light shielding layer 11 are integrated, the optical waveguide 9 and the light shielding layer 11 are simultaneously inserted into the device under test 2. If the optical waveguide 9 and the light shielding layer 11 are separate, the light shielding layer 11 is first inserted into the device under test 2, and then the optical waveguide 9 is inserted into the light shielding layer 11. At this time, by confirming the image of the X-ray camera 14, the position of the tip of the biological light acquisition probe 4 can be accurately aligned with respect to the sample portion 2a. Through the above steps, preparation for acquiring a biological light image is completed. Then, the dark box 3 is closed to form a light shielding space 3a.

  Subsequently, the processing control unit 17 controls the image acquisition device 6 to acquire a biological light image. Since biological light has a weak light intensity, an image is acquired by long exposure of several seconds to several tens of seconds, several minutes to one hour, and in some cases, several days depending on the light intensity. As described above, since long-time exposure is suitable for acquiring a biological light image, intrusion of disturbance light from the periphery of the light incident surface 9b of the biological light acquisition probe 4 to the light incident surface 9b is prevented by the light shielding wall portion 11a. Thus, the effect of reduction is more exhibited.

  According to the biological light image acquisition system 1, the biological light acquisition probe 4, and the biological light image acquisition method, the biological light incident from the light incident surface 9 b of the biological light acquisition probe 4 enters the image acquisition device 6, and the biological light A biological light image indicating the state of light is acquired. Here, the biological light emitted from the specimen part 2a by chemiluminescence has a low light intensity. Therefore, in order to capture biological light, it is important to reduce background light that becomes noise.

  The light that can be background light in the biological light image includes ambient light in the environment where the inspection object 2 is disposed. In this biological light image acquisition system 1, the inspection object 2 forms a dark box 3 in which a light shielding space 3a is formed. Since it is housed inside, the influence of ambient light is eliminated. In addition, light may be generated in a place other than the specimen portion 2a to be inspected in the inspected object 2, and when this light emission is guided to the image acquisition device 6, it can become background light in a biological light image. According to this biological light image acquisition system 1, since the light shielding layer 11 is provided so as to cover the side surface 9 a of the optical waveguide unit 9, incidence of light emission from the side surface 9 a of the optical waveguide unit 9 is suppressed. Further, a light shielding wall 11 a is formed on the light shielding layer 11 on the distal end side of the biological light acquisition probe 4. The light shielding wall portion 11a is formed so as to protrude from the light incident surface 9b including the distal end portions 8a of the plurality of optical fibers 8 and surround the light incident surface 9b, and the light shielding wall portion 11a serves as the sample portion 2a. Since they are in contact with each other, the incidence of light generated at a place other than the specimen portion 2a facing the light incident surface 9b to the light incident surface 9b is suppressed.

Accordingly, since light that can be background light is suppressed from being incident on the image acquisition device 6, the background light with high light intensity does not bury biological light with low light intensity and has a good S / N ratio. A biological light image can be acquired. Eventually, the use of the biological optical image acquisition system 1 in the luminescence imaging method that is widely used as the main method in bioimaging increases the examination accuracy and examination efficiency, so that advances in gene expression and pathological condition elucidation techniques can be expected.
[Modification]

  The present invention is not limited to the above-described embodiment, and various modifications as described below are possible without departing from the gist of the present invention.

  As shown in FIG. 3A, in the biological light acquisition probe 4 </ b> A, the tip of the optical waveguide unit 9 is not formed obliquely, and the light incident surface 9 b is orthogonal to the optical axis of the optical fiber 8. It may be formed. According to such a biological light acquisition probe 4, the specimen portion 2 a that acquires biological light can be a surface orthogonal to the insertion direction of the biological light acquisition probe 4. Further, as shown in FIG. 3B, the biological light acquisition probe 4 may be disposed on the object to be inspected 2 so that a part of the light incident surface 9b is in close contact with the sample portion 2a. In some cases, the bundle fiber is disposed after the light shielding outer tube is inserted first without connecting the light shielding outer tube forming the light shielding layer 11 and the bundle fiber forming the optical waveguide 9. In this case, the light shielding outer tube and the bundle fiber may be used without being bonded to each other.

  Further, as shown in FIG. 4A, the biological light acquisition probe 4B includes a lens 18 disposed so as to be positioned between the light incident surface 9b and the sample portion 2a, and the light shielding wall portion 11a is a lens. It may protrude from the light incident surface 9b so as to be larger than the thickness of 18. According to such a configuration, the tip of the light shielding wall portion 11a contacts the sample portion 2a, and a gap S is formed between the lens 18 and the sample portion 2a. A desired chemical solution or the like can be injected into the gap S.

  Further, as shown in FIG. 4B, the biological light acquisition probe 4 </ b> C may be arranged on the device under test 2 so that the lens 18 is in close contact with the device under test 2. According to such a configuration, it is possible to acquire an image of biological light at a position deeper by the focal length of the lens 18 than the surface to which the lens 18 is in close contact.

  As shown in FIG. 5A, the biological light acquisition probe 4D captures the irradiation light waveguide unit 19a for guiding the irradiation light for fluorescence observation in addition to the optical waveguide unit 9, and the fluorescence. An optical waveguide 19 such as a fluorescence waveguide 19b for acquiring a captured image may be provided. In such a multifunctional biological light acquisition probe 4 </ b> D, the optical waveguide 9 is disposed in the vicinity of the central axis of the light shielding layer 11, and six other optical waveguides 19 are provided between the optical waveguide 9 and the light shielding layer 11. Is arranged. These other optical waveguide portions 19 function as the irradiation light waveguide portion 19a and the fluorescence waveguide portion 19b. A hollow tube 21 and an electrode 22 are arranged between the optical waveguide unit 9 and another optical waveguide unit 19. Water and chemicals can be sent to the tip of the biological light acquisition probe 4 through the tube 21 and electric stimulation can be applied to the cell tissue, so that various examinations can be handled. A light-shielding resin 23 is filled between the optical waveguide portions 9 and 19, the tube 21, and the electrode 22. In addition, this imaging method acquires the biological light acquisition probe 4D and each optical waveguide 9 as an image on a single screen or a plurality of screens, and acquires a plurality of optical information by simultaneously or switching detection of light emission and fluorescence. To do.

  As shown in FIG. 5B, the light shielding layer 11E of the biological light acquisition probe 4E may have a spiral cross-sectional shape. Optical waveguides 9 and 19 are disposed between the light shielding layers 11E, and a resin 23 having light shielding properties is filled in the gaps.

  Moreover, even if the biological light image acquisition system 1 has a structure in which the image acquisition device 6 including the image optical system is integrally accommodated in the dark box 3 that forms the light-shielding space 3a, the biological light image acquisition system 1 accommodates the object to be inspected 2 and is shielded from light. The image acquisition device 6 including an optical system placed separately from the dark box 3 forming the space 3a is connected to the optical waveguide 9 extended from the dark box 3.

[Comparative example]
A biological light acquisition probe in which no light shielding wall is formed is created, and the biological light acquisition probe is inserted into the inspected object 2 to which a medicine containing a luminescent substance is not administered, and an image G1 is acquired (see FIG. 6A). . That is, in this image, biological light emitted from the cell tissue is not captured, and only background light is captured.

[Experimental Example 1]
A biological light acquisition probe 4 having a light shielding wall 11a was created, and an image G2 was acquired using the biological light image acquisition system 1. As in the comparative example described above, since the medicine containing the luminescent substance is not administered to the subject 2, only the background light is captured in the acquired image. As shown in FIG. 6B, when the biological light acquisition probe 4 having the light shielding wall 11a is used, the intensity of the background light indicated by the luminance value is 1 compared to the image G1 of the comparative example. / 100 was found to be reduced to about 100.

[Experiment 2]
Using the biological optical image acquisition system 1 used in Experimental Example 1, a biological optical image was acquired on an object to be inspected to which a medicine containing a luminescent substance was administered. As shown in FIG. 7, a biological light image G3 capable of confirming the localization of the luminescence L from the cell tissue could be obtained with the low background fire. According to this result, it has been found that it is possible to discriminate the light emission site at the cell level (sometimes at the optical fiber strand diameter level).

DESCRIPTION OF SYMBOLS 1 ... Living body light image acquisition system, 2 ... Test object, 2a ... Sample part, 3 ... Dark box, 3a ... Light-shielding space, 4, 4A-4E ... Living body light acquisition probe, 6 ... Image acquisition apparatus, 6a ... Light input part , 7 ... light absorption box, 8 ... optical fiber, 8a ... tip part, 8b ... other end part, 9, 19 ... optical waveguide part, 9a ... side face, 9b ... light incident surface, 11, 11E ... light shielding layer, 11a ... Light shielding wall part, 12 ... Cooling device, 13 ... Manipulator, 13a ... Illuminated camera system, 14 ... X-ray camera, 16 ... Optical system, 16a, 16b, 18 ... Lens, 17 ... Processing control part, 21 ... Tube, 22 ... electrode, 23 ... resin.

Claims (8)

In a system for acquiring a biological light image indicating a state of biological light emitted from a specimen part of an object to be inspected,
A dark box that houses the object to be inspected and forms a light shielding space;
A plurality of optical fibers are bundled in a radial direction so as to cover an optical waveguide that guides the biological light incident on the tip of the optical fiber to the other end of the optical fiber, and a side surface of the optical waveguide A light-shielding layer provided, and a biological light acquisition probe arranged in the dark box,
An image acquisition device that receives the biological light emitted from the other end and acquires the biological light image using the biological light;
With
The light shielding layer has a light shielding wall portion that protrudes from a light incident surface including the tip portions of the plurality of optical fibers and is formed so as to surround the light incident surface.
The biological optical image acquisition system characterized by the above-mentioned. The dark box has a light absorbing portion disposed in the light shielding space,
The object to be inspected is disposed in the light absorbing portion.
The biological optical image acquisition system according to claim 1. The image acquisition device has a light input unit on which the biological light is incident,
The light input unit is disposed in the dark box,
The living body optical image acquisition system according to claim 1 or 2.   4. The angle between the light incident surface of the optical waveguide unit and the optical axis direction of the optical fiber is 0 degree or more and less than 90 degrees, according to claim 1. Biological optical image acquisition system. In the biological light acquisition probe for acquiring biological light emitted from the specimen portion of the object to be inspected,
A plurality of optical fibers are bundled in a radial direction, and an optical waveguide that guides the biological light incident on the tip of the optical fiber to the other end of the optical fiber;
A light shielding layer provided so as to cover a side surface of the optical waveguide unit,
The optical waveguide portion has a light incident surface including the tip portions of the plurality of optical fibers,
The biological light acquisition probe, wherein the light shielding layer has a light shielding wall portion that protrudes from the light incident surface and that surrounds the light incident surface. In the biological light image acquisition method for acquiring a biological light image indicating the state of biological light emitted from the specimen portion of the object to be inspected,
Accommodating the object to be inspected in a dark box for forming a light shielding space;
A step of bringing the tip of the light shielding wall portion of the light shielding layer of the biological light acquisition probe into contact with the specimen portion;
Acquiring the biological light image using an image acquisition device on which the biological light emitted from the biological light acquisition probe is incident;
Have
The biological light acquisition probe includes: an optical waveguide unit in which a plurality of optical fibers are bundled in a radial direction, and guides the biological light incident on a distal end portion of the optical fiber to the other end portion of the optical fiber; A light shielding layer provided so as to cover the side surface of the part,
The light shielding wall portion is formed so as to protrude from a light incident surface including the tip portions of the plurality of optical fibers and surround the light incident surface.
A method for acquiring a biological optical image. The optical waveguide is attached to and integrated with the light shielding layer,
In the step of contacting the specimen portion, the optical waveguide portion and the light shielding layer are simultaneously inserted into the object to be inspected.
The method for acquiring a biological optical image according to claim 6. The optical waveguide is separate from the light shielding layer,
In the step of contacting the specimen portion, the light shielding layer is inserted into the object to be inspected,
After the step of contacting the specimen portion and before the step of acquiring the biological light image, the optical waveguide portion is placed in the light shielding layer so that the light shielding wall portion protrudes from the light incident surface. Having a step of inserting into
The method for acquiring a biological optical image according to claim 6.