WO2024142584A1 - Dispositif de détection de fluorescence - Google Patents

Dispositif de détection de fluorescence Download PDF

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Publication number
WO2024142584A1
WO2024142584A1 PCT/JP2023/039159 JP2023039159W WO2024142584A1 WO 2024142584 A1 WO2024142584 A1 WO 2024142584A1 JP 2023039159 W JP2023039159 W JP 2023039159W WO 2024142584 A1 WO2024142584 A1 WO 2024142584A1
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WO
WIPO (PCT)
Prior art keywords
light
fluorescence
optical fiber
scope
excitation light
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PCT/JP2023/039159
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English (en)
Japanese (ja)
Inventor
裕明 里村
智也 保坂
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株式会社アドバンテスト
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Application filed by 株式会社アドバンテスト filed Critical 株式会社アドバンテスト
Publication of WO2024142584A1 publication Critical patent/WO2024142584A1/fr

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  • the present invention relates to a fluorescence detection device.
  • Tubes 11 and 11a form a double tube in which tube 11a is disposed within tube 11, the light-transmitting optical fiber 12 is restrained within tube 11a, and at least one light-receiving optical fiber 13 is restrained between tube 11a and tube 11.
  • the restraint of the optical fibers by tubes 11 and 11a will be described in more detail below.
  • the light transmitting optical fiber 12 may be an optical fiber formed from a material such as quartz glass, glass containing other components, fluoride glass, chalcogenide glass, or plastic.
  • the light transmitting optical fiber 12 may be an optical fiber such as a multimode fiber (MMF), a single mode fiber (SMF), a double clad fiber (DCF), or a photonic crystal fiber (PCF).
  • MMF multimode fiber
  • SMF single mode fiber
  • DCF double clad fiber
  • PCF photonic crystal fiber
  • the scope 10 can insert the tip of its longitudinal axis into the abdominal cavity 1a of the subject 1, output the excitation light ⁇ 0 from the tip, and collect the fluorescence ⁇ emitted by the drug 2 in the tissue by irradiating the excitation light ⁇ 0 from the tip.
  • the scope 10 may output guide light ⁇ g in the visible light wavelength range superimposed on the excitation light ⁇ 0 to irradiate the tissue in the abdominal cavity 1a. This allows the tip of the scope 10 to approach a site of interest in the abdominal cavity 1a and examine only that site of interest.
  • the scope 10 has the light-receiving optical fiber 13 that collects the fluorescence ⁇ emitted from the tissue in response to irradiation with the excitation light ⁇ 0 and guides it to the detector 35, independently of the light-transmitting optical fiber 12 that guides the excitation light ⁇ 0 output from the light source 34 and emits it toward the tissue in the abdominal cavity 1a.
  • the cable 20 is a device for connecting the scope 10 to the device body 30 and optically connecting the light-transmitting optical fiber 12 and the light-receiving optical fiber 13 (13a to 13g) to the light source 34 and the detector 35, respectively.
  • the cable 20 includes a flexible tube 21, a light-transmitting optical fiber 22, a light-receiving optical fiber 23, and a gripping portion 24.
  • the flexible tube 21 is a flexible tubular member that bundles the light-transmitting optical fiber 22 and the light-receiving optical fiber 23 and holds them inside.
  • the flexible tube 21 may be, for example, a sheathed SUS tube having a diameter of 5 mm and a length of 300 cm.
  • One end of the flexible tube 21 is connected to the connector 14 of the scope 10, and is formed using an insulating material such as resin (for example, ABS resin) to prevent electric shock.
  • the other end of the flexible tube 21 is connected to the connector 29 of the device main body 30.
  • the grip 24 is provided at one end of the cable 20 and is a member that is gripped by the user operating the scope 10 to operate the scope 10.
  • the handle portion that forms the outer surface of the grip 24 may be formed using an insulating material such as a general-purpose plastic such as polyethylene, a thermoplastic resin such as polycarbonate or polyether ether ketone (so-called engineering plastic), or a thermosetting resin such as phenol.
  • the connector 14 of the scope 10 is removably fixed to the grip 24.
  • the light-transmitting optical fiber 22 and the light-receiving optical fiber 23 are positioned coaxially with the light-transmitting optical fiber 12 and the light-receiving optical fiber 13 (13a-13g) of the scope 10, respectively, and are also positioned coaxially with the optical fibers 32, 33 (33a-33g) of the device body 30.
  • the light-transmitting optical fiber 12 of the scope 10 is optically connected (also called optically connected) to the light source 34 (excitation light source 34a and guide light source 34b), and the light-receiving optical fiber 13 is optically connected to the detector 35.
  • the device main body 30 is a unit equipped with various functional devices within a housing 31, including a light source 34, a detector 35, a control and calculation device 36, a recording device 37, an input/output device 38, and a communication device 39. These functional devices are connected to each other via communication lines so that they can communicate with each other.
  • the housing 31 houses functional devices such as the light source 34.
  • a connector 29 to which the flexible tube 21 is connected is fixed to the front via an insulating material such as resin (e.g., polycarbonate).
  • a power connector (not shown) is fixed to the rear, through which power is sent from a commercial power source (100V AC) to each functional device.
  • the housing 31 is grounded as a frame ground. Further connectors such as a universal serial bus (USB), digital visual interface (DVI)-D, and DVI-I are provided on the rear.
  • USB universal serial bus
  • DVI digital visual interface
  • an intake port for taking in air is provided on the front of the housing 31, and an exhaust port for sending air out is provided on the rear.
  • a fan By operating a fan (not shown), air flows inside the housing from the front to the rear, cooling each functional device.
  • a lamp (not shown) that uses light to indicate that the housing is in operation or that an abnormality has occurred, and a speaker (not shown) that uses sound to indicate this, are provided on the front of the housing 31.
  • a laser key switch, a laser emergency stop button, and a start switch are provided on the front of the housing 31, and an AC inlet switch, a laser interlock, and a potential equalization terminal (all not shown) are provided on the rear of the housing 31.
  • the light source 34 is a device that generates the excitation light ⁇ 0 and the like, and includes an excitation light source 34a and a guide light source 34b.
  • the excitation light source 34a employs a laser diode (e.g., 40 mW variable) that outputs near-infrared light (e.g., wavelength 785 nm) as the excitation light ⁇ 0.
  • the guide light source 34b employs a laser diode (e.g., 10 mW variable) that outputs visible light (light in the visible light wavelength range, e.g., green light with a wavelength of 520 nm) as the guide light ⁇ g .
  • the light source 34 outputs a guide light ⁇ g containing visible light superimposed on the excitation light ⁇ 0 so that the irradiation location of the excitation light ⁇ 0 can be seen.
  • the light source 34 detects the intensity of the excitation light ⁇ 0 , the temperature of the excitation light source 34a, an abnormality in the power supply, and the like, and transmits the detection results to the control and arithmetic device 36.
  • the pumping light source 34a and the guide light source 34b send out pumping light ⁇ 0 and guide light ⁇ g to the optical fibers 32a and 32b, respectively, combine them via an optical fiber coupler (not shown), and send them to the light-transmitting optical fiber 22 of the cable 20 via the optical fiber 32.
  • the pumping light source 34a and the guide light source 34b generate the pumping light ⁇ 0 and the guide light ⁇ g in accordance with a drive signal transmitted from the control and arithmetic device 36.
  • the pumping light source 34a may periodically output (on and off) the pumping light ⁇ 0 .
  • the detector 35 is a device that detects the fluorescence ⁇ .
  • the detector 35 receives the fluorescence ⁇ collected by the scope 10 (light-receiving optical fibers 13a-13g) via the light-receiving optical fibers 23 (23a-23g) of the cable 20 and the optical fibers 33 (33a-33g) of the device body 30.
  • the detector 35 detects each of the fluorescence guided by each of the multiple light-receiving optical fibers 13a-13g.
  • the detector 35 has multiple sets of optical filters (not shown) and detectors 35a-35h.
  • the fluorescence ⁇ guided by the optical fibers 33a-33g is split via an optical fiber coupler (not shown), and guided by the optical fiber 33h to the detector 35h for spectral analysis.
  • the results of the detection of the fluorescence ⁇ by the detectors 35a-35h are sent to the control and calculation device 36.
  • the detectors 35 alternately obtain detection data during irradiation (on signal) and non-irradiation (off signal) in accordance with a drive signal transmitted from the control and calculation device 36, i.e., in response to the periodic on-off of the excitation light ⁇ 0.
  • the detection results are transmitted to the control and calculation device 36.
  • the control and calculation device 36 integrates the detection data during the on signal and the off signal, respectively, and calculates the difference between the integrated detection data, thereby canceling noise resulting from ambient light.
  • the control and arithmetic unit 36 is a computer device that controls each functional unit and analyzes the fluorescence state using the detection results of the fluorescence ⁇ by the detector 35, and has a central processing unit (CPU).
  • the CPU executes a dedicated program to cause the control and arithmetic unit 36 to perform a control and arithmetic function.
  • the functional configuration of the control and arithmetic unit 36 will be described later.
  • the dedicated program is activated, for example, by being stored in a ROM (not shown) and read out by the CPU, or by being stored in a storage medium such as a CD-ROM and read out by the CPU using a reading device (not shown) and expanding it into RAM.
  • the control unit 36a may change light emission parameters including any one of the color, intensity, brightness, spread, beam shape, and light emission pattern of the guide light ⁇ g when the excitation light ⁇ 0 is being irradiated and when it is not being irradiated, so that the user can recognize that the excitation light ⁇ 0 is being irradiated through a laparoscopic image described later.
  • the control unit 36a may change the color of the guide light ⁇ g from green to a brighter color (e.g., orange), the intensity to be stronger, the brightness to be brighter, the spread to be narrower, the beam shape from a circle to an x or +, and the light emission pattern to be blinking at regular intervals.
  • a brighter color e.g., orange
  • the analysis unit 36b may analyze the spectral shape of the fluorescence ⁇ to identify the location or tissue in the abdominal cavity 1a that emits the fluorescence ⁇ , i.e., the location or tissue in the abdominal cavity 1a in which the drug 2 is located.
  • the analysis unit 36b processes the detection results of the fluorescence ⁇ (i.e., the fluorescence intensity) by the detectors 35a to 35g to detect dirt on the light-receiving optical fibers 13a to 13g.
  • the analysis unit 36b identifies a significantly smaller fluorescence intensity from among the fluorescence intensities I1 to I7 detected by the detectors 35a to 35g. Whether or not it is significantly smaller can be determined, for example, by whether it is smaller than a predetermined threshold value. It can also be determined by whether it is smaller than a predetermined threshold value, such as the average of the fluorescence intensities I1 to I7.
  • the analysis unit 36b identifies any of the fluorescence intensities I1 to I7 as significantly smaller, it identifies the corresponding light-receiving optical fiber 13a to 13g and displays it on the display screen 41 of the monitor device 40 via the display unit 36c. For example, as shown in FIG. 5, a cross mark is displayed on the identified light-receiving optical fiber (light-receiving optical fiber 13d in this example). This allows the user to determine that dirt has adhered to the tips of the displayed light-receiving optical fibers 13a to 13g, causing a decrease in the collection efficiency of the fluorescent light ⁇ , and to remove the scope 10 from the abdominal cavity 1a and clean it.
  • the analysis unit 36b also analyzes the detection results of the fluorescence gamma (i.e., the fluorescence intensity) by the detectors 35a to 35g to determine the emission distribution of the fluorescence gamma.
  • the analysis unit 36b compares the values of the fluorescence intensities I1 to I7 detected by the detectors 35a to 35g, respectively, to identify the highest intensity, the second highest intensity, and the third highest intensity, and displays the results on the display screen 41 of the monitor device 40 via the display unit 36c.
  • the user can determine that the fluorescence intensity of the light-receiving optical fiber 13a is the greatest, followed by the fluorescence intensity of the light-receiving optical fibers 13b and 13g, and that the source of the fluorescence ⁇ , i.e., the drug 2, is located on the side of the light-receiving optical fiber 13a from the tip of the scope 10, and the fluorescence ⁇ can be collected more efficiently by moving the tip of the scope 10 in that direction.
  • the source of the fluorescence ⁇ i.e., the drug 2
  • the recording unit 36d is a unit that uses the recording device 37 to record various information such as the results of the detection of fluorescence ⁇ by the detector 35, the results of the analysis of the fluorescence state by the analysis unit 36b, and the detection conditions.
  • the recording unit 36d also reads out various data recorded in the recording device 37 and transmits it to the analysis unit 36b, etc.
  • FIG. 6 shows the use of the fluorescence detection device 100 in combination with the laparoscope device 200.
  • the laparoscope device 200 is a device independent of the fluorescence detection device 100 according to this embodiment, and includes a scope 110, cables 120 and 121, and a device main body 130.
  • the scope 110 is an optical tube that is at least partially inserted into the abdominal cavity 1a of the subject 1, emits illumination light W to illuminate the abdominal cavity 1a, and collects reflected light.
  • the scope 110 includes a tube 111, a light-transmitting optical fiber and a light-receiving optical fiber (not shown), and a connector 114.
  • the tube 111 is a tubular member that aligns the tips of the light-transmitting optical fiber and the light-receiving optical fiber on one end face (i.e., the tip face) of the longitudinal axis and supports them internally.
  • the tip of the tube 111 is inserted into the abdominal cavity 1a of the subject 1, and the base end is fixed to the connector 114.
  • the light-transmitting optical fiber and the light-receiving optical fiber are configured in the same manner as the light-transmitting optical fiber 12 and the light-receiving optical fiber 13 described above.
  • the light-transmitting optical fiber sends illumination light (white light) W output from the light source 131 into the abdominal cavity 1a, and the light-receiving optical fiber collects reflected light from within the abdominal cavity 1a and sends it to the camera 132.
  • the connector 114 is a member that supports the base end of the scope 110, and one end of the cables 120 and 121 is detachably fixed to the connector 114.
  • the cable 120 to the connector 114 By connecting the cable 120 to the connector 114, the light-transmitting optical fiber in the scope 110 is optically connected to the light source 131, and by connecting the cable 121 to the connector 114, the light-receiving optical fiber in the scope 110 is optically connected to the camera 132.
  • Cables 120 and 121 are devices for connecting scope 110 to device body 130 and optically connecting the light transmitting optical fiber and light receiving optical fiber of scope 110 to light source 131 and camera 132, respectively. Cables 120 and 121 are flexible, and each transmits illumination light W output from light source 131 to the light transmitting optical fiber of scope 110, and transmits reflected light focused on the light receiving optical fiber of scope 110 to camera 132.
  • the device main body 130 is a unit equipped with various functional devices within a housing 130a, including a light source 131, a camera 132, and a communication device 133. These functional devices are connected to each other via communication lines so that they can communicate with each other.
  • the housing 130a houses functional devices such as the light source 131. Connectors to which the cables 120 and 121 are connected are fixed to the front. A power connector (not shown) is fixed to the rear, through which power is sent from a commercial power source (100V AC) to each functional device. Further connectors such as USB, DVI-D, and DVI-I are provided on the rear.
  • the light source 131 is a device that generates illumination light W, and may be, for example, an LED that outputs white light.
  • the illumination light W is sent to the scope 110 via the cable 120.
  • the communication device 133 is a device for communicating with the fluorescence detection device 100, and is connected to the fluorescence detection device 100 via a cable such as USB, DVI-D, or DVI-I, and can transmit various data such as laparoscopic images.
  • the laparoscopic device 200 and the fluorescence detection device 100 are connected using a DVI-D cable (not shown) or the like.
  • the monitor device 40 is connected to the fluorescence detection device 100. This allows an image of the inside of the abdominal cavity 1a captured by the laparoscopic device 200 (camera 132) (i.e., a laparoscopic image) to be transmitted to the fluorescence detection device 100 and displayed on the display screen 41 of the monitor device 40 together with the analysis results of the fluorescence state processed by the fluorescence detection device 100, etc.
  • the user inserts the tip of the longitudinal axis of the scope 110 of the laparoscopic device 200 and the tip of the longitudinal axis of the scope 10 of the fluorescence detection device 100 into the abdominal cavity 1a of the subject 1, respectively.
  • a cylindrical holder may be fitted into the outer skin of the abdomen of the subject 1, and the scopes 110, 10 may be inserted into the abdominal cavity 1a through it.
  • the user operates the light source 131 of the laparoscopic device 200 to generate illumination light W, which is sent to the scope 110 via the cable 120.
  • the display unit 36c displays the results of fluorescence gamma detection, particularly the peak intensity in the fluorescence spectrum (also called fluorescence intensity).
  • the change in fluorescence intensity over time is displayed in real time.
  • the fluorescence intensity is displayed as a color bar, that is, as the fluorescence intensity increases, the bar extends from bottom to top, changing color (gradation) from blue to red.
  • Area 45 displays the detection results of fluorescence gamma by display unit 36c.
  • the spectrum of fluorescence gamma intensity distribution with respect to wavelength, also simply called the fluorescence spectrum
  • the upper part of area 45 also includes a display 45a (see Figure 5) of the analysis results of the fluorescence intensity mentioned above.
  • the upper area 46 displays the wavelength (also called peak wavelength) and intensity (also called peak intensity) of the peak position of the fluorescence spectrum. Also, the changes over time of the fluorescence spectrum and peak intensity are displayed in real time.
  • the display unit 36c may read various information such as laparoscopic images, fluorescence gamma detection results, fluorescence state analysis results, and detection conditions recorded by the recording device 37 via the recording unit 36d, and play back and display them on the display screen 41 of the monitor device 40.
  • step S2 the control unit 36a displays an image (i.e., a laparoscopic image) of the inside of the abdominal cavity 1a of the subject 1 captured by the laparoscopic device 200 on the display screen 41 (area 42) of the monitor device 40 connected to the fluorescence detection device 100, as shown in FIG. 7.
  • the guide light ⁇ g in the visible light wavelength range is output from the tip of the scope 10 so that the position in the abdominal cavity 1a to which the tip of the scope 10 is directed, i.e., the irradiation spot (spot Sp) of the excitation light ⁇ 0 and the irradiation direction can be visually confirmed.
  • the user confirms the position of the spot Sp in the laparoscopic image displayed on the monitor device 40, and moves the scope 10 to direct and/or bring the tip of the scope 10 close to the site of interest in the abdominal cavity 1a. Then, the user turns on the SW 24a to irradiate the site of interest with the excitation light ⁇ 0 .
  • step S3 the control unit 36a judges whether or not SW24a has been turned on. If the control unit 36a judges that SW24a has been turned on, it proceeds to step S4 assuming that the user has turned SW24a on, and if it judges that SW24a has not been turned on, it repeats step S3 assuming that the user has not turned SW24a on. Note that if a certain amount of time has passed without proceeding to step S4 or if step S3 has been repeated a predetermined number of times, it may return to step S2.
  • step S4 the control unit 36a transmits a drive signal to the light source 34 to generate excitation light ⁇ 0 , which is superimposed on the guide light ⁇ g and emitted from the tip of the scope 10 to irradiate the spot Sp.
  • excitation light ⁇ 0 is superimposed on the guide light ⁇ g and emitted from the tip of the scope 10 to irradiate the spot Sp.
  • "laser irradiation in progress" is displayed in an area 44 of the display screen 41.
  • the drug 2 located in the tissue in the spot Sp absorbs the excitation light ⁇ 0 and emits fluorescence ⁇ .
  • the fluorescence ⁇ emitted by the drug 2 is collected from the tip of the scope 10 and sent to the detector 35.
  • the light source 34 generates the excitation light ⁇ 0 and simultaneously detects its intensity, and transmits the detection result to the control and calculation device 36 (analysis unit 36b).
  • the fluorescence state may include the spectral shape of the fluorescence ⁇ .
  • the analysis unit 36b may analyze the spectral shape of the fluorescence ⁇ to identify the location or tissue that emits the fluorescence ⁇ , i.e., the location or tissue where the drug is located. The result may be displayed on the display screen 41 in the next step S7.

Abstract

Un dispositif de détection de fluorescence 100 comprend : une source de lumière 34 qui produit une lumière d'excitation γ0 ; un endoscope 10 qui est inséré au moins partiellement dans la cavité abdominale 1a d'un sujet 1, l'endoscope comportant une fibre optique d'émission de lumière 12 servant à guider la lumière d'excitation émise par la source de lumière 34 jusqu'à un tissu situé dans la cavité abdominale du sujet et au moins une fibre optique de réception de lumière 13 servant à guider la fluorescence γ émise par le tissu du fait de son exposition à la lumière d'excitation ; et un détecteur 35 qui détecte la fluorescence recueillie par l'endoscope. Comme, dans l'endoscope, la fibre optique de réception de lumière 13 est indépendante de la fibre optique d'émission de lumière 12, il est possible de détecter la fluorescence guidée par la fibre optique de réception de lumière 13 sans détecter la lumière d'excitation réfléchie sur la surface de l'extrémité d'émission de lumière de la fibre optique d'émission de lumière 12.
PCT/JP2023/039159 2022-12-28 2023-10-30 Dispositif de détection de fluorescence WO2024142584A1 (fr)

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Application Number Priority Date Filing Date Title
JP2022-212678 2022-12-28

Publications (1)

Publication Number Publication Date
WO2024142584A1 true WO2024142584A1 (fr) 2024-07-04

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