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WO2016082558A1 - Laser nanometer-scale optical diagnostic device - Google Patents

Laser nanometer-scale optical diagnostic device Download PDF

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Publication number
WO2016082558A1
WO2016082558A1 PCT/CN2015/083870 CN2015083870W WO2016082558A1 WO 2016082558 A1 WO2016082558 A1 WO 2016082558A1 CN 2015083870 W CN2015083870 W CN 2015083870W WO 2016082558 A1 WO2016082558 A1 WO 2016082558A1
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Prior art keywords
laser
treatment
nano
disposed
ccd
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PCT/CN2015/083870
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French (fr)
Chinese (zh)
Inventor
蔡林涛
郑明彬
赵鹏飞
罗震宇
龚萍
郑翠芳
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深圳先进技术研究院
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Publication of WO2016082558A1 publication Critical patent/WO2016082558A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062Arrangements for scanning
    • A61B5/0064Body surface scanning
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • A61N5/062Photodynamic therapy, i.e. excitation of an agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/067Radiation therapy using light using laser light

Definitions

  • the present invention relates to the field of physical diagnosis and treatment technology, and in particular to a laser nano-optical diagnosis and treatment device.
  • Photothermal therapy refers to the use of the thermal effects of various pyrogens to heat the tumor area or whole body to the temperature of effective treatment, and maintain a certain time, using the difference in temperature tolerance between normal tissue and tumor tissue, to achieve both killing Tumor cells do not damage the treatment of normal tissues.
  • Photodynamic therapy refers to a method in which a photosensitizer is used to cause a functional or morphological change of an organism cell or a biomolecule under the action of light to achieve a therapeutic effect.
  • Photodynamic therapy is another new research that is completely different from surgery, radiotherapy, chemotherapy and immunotherapy. It has become one of the most active research fields in the world of cancer prevention and treatment.
  • the main object of the embodiments of the present invention is to provide a laser nano-optical diagnosis and treatment device to provide a diagnosis and treatment device that integrates photothermal therapy technology, photodynamic therapy technology and living body imaging technology.
  • an embodiment of the present invention provides a laser nano-optical diagnosis and treatment device, including:
  • a carrying platform disposed in the treatment dark room for carrying a therapeutic object injected with a nano photosensitizer in vivo;
  • a first laser disposed in the treatment dark chamber for emitting laser light to illuminate the treatment object, causing the nano photosensitizer injected into the body of the treatment object to emit light;
  • a charge coupled image sensor CCD disposed in the treatment darkroom
  • a filter disposed between the treatment target and the CCD for filtering light of a set spectrum to transmit light emitted by the nano photosensitizer
  • the CCD is configured to photograph the treatment object through the filter
  • An image processor connected to the CCD, for acquiring an image captured by the CCD, and performing image processing on the image to locate an area enriched in the body of the treatment object;
  • the rotating table adjusts a transmitting direction of the second laser by rotating
  • a central controller that connects the image processor and the rotating table, positions an area in which the illumination object is enriched in the treatment object as a tumor area, and controls rotation of the rotating table to adjust an emission direction alignment of the second laser Tumor area;
  • the second laser is configured to emit laser light to illuminate the tumor region, so that the nano photosensitizer exerts photothermotherapy and/or photodynamic therapy;
  • the central controller is further connected to the first laser and the second laser for controlling the first laser and the second laser to be turned on or off.
  • the laser nano-optical diagnosis and treatment device emits laser to inject nano-photosensitive agent injected into the treatment object, and monitors the metabolism, distribution and enrichment of the nano photosensitizer in real time, thereby accurately positioning the tumor.
  • the position is achieved by non-invasive and non-invasive tumor treatment of the treated subject by emitting laser light to the nano-photosensitive agent in the tumor region to perform photothermal therapy or photodynamic therapy.
  • FIG. 1 is a schematic structural view of a laser nano-optical diagnosis and treatment device provided by the present invention
  • FIG. 2 is a schematic structural view of a laser nano-optical diagnosis and treatment device according to Embodiment 1 of the present invention.
  • the nano photosensitizer used in the present invention is a biocompatible macromolecule such as phospholipid, phospholipid polymer, polypolysaccharide, polypeptide, albumin, etc., and surface-modified folic acid, Her2 ligand, etc.
  • Photosensitive agents such as phthalocyanine green, IR780, porphyrin and nano gold can prepare degradable nano photosensitizers, which can achieve targeted recognition and enrichment of tumors, and have the advantages of good fluorescence stability and low toxicity.
  • the following is a preparation method of a nano photosensitizer used in the present invention: dissolving phthalocyanine green, soybean lecithin and distearyl phosphatidylethanolamine-polyethylene glycol-folic acid in a mass ratio of 1:1.7:1.7
  • the organic solvent was removed by rotary evaporation in an organic solvent to obtain a film material.
  • 2.5mL ultrapure water was added, ultrasonicated by ultrasonic sonicator for 5min, and ultrafiltered by ultrafiltration for 3 times, which resulted in the inclusion of phthalocyanine green phospholipid folic acid targeting nano photosensitizer.
  • the invention provides a laser nano-optical diagnosis and treatment device.
  • the device comprises: a treatment darkroom 101, a carrying platform 102, a first laser 103, a charge-coupled image sensor CCD (Charge-coupled Device) 104, and a filter. 105.
  • the treatment darkroom 101 may be made of plastic, metal, wood or stone.
  • the carrying platform 102 is disposed in the treatment dark room 101 for carrying a therapeutic object injected with a nano photosensitizer in vivo.
  • the first laser 103 is disposed in the treatment dark room 101 for emitting laser irradiation to the treatment subject to illuminate the nano photosensitizer injected into the treatment subject.
  • the CCD 104 is disposed in the treatment dark room 101.
  • the filter 105 is disposed between the treatment target and the CCD 104 for filtering out the light of the set spectrum to transmit the light emitted by the nano photosensitizer.
  • the filter 105 can achieve the purpose of filtering out stray light and improve the accuracy of positioning the tumor according to the light emitted by the nano photosensitizer.
  • the filter 105 needs to cooperate with the nano photosensitizer injected into the body of the treatment object to achieve the purpose of transmitting the light emitted by the nano photosensitizer and filtering out the stray light.
  • the CCD 104 is configured to photograph the treatment subject through the filter 105.
  • the image processor 106 is connected to the CCD 104 for acquiring an image captured by the CCD 104, and performing image processing on the image to locate an area enriched in the body of the treatment object.
  • the nano photosensitizer can achieve targeted recognition and enrichment of the tumor, and thus the region enriched in the luminescence in the image of the treated subject is the tumor region.
  • the rotary table 108 is disposed in the treatment dark room 101; the second laser 109 is mounted on the rotary table 108; and the rotary table 108 adjusts the emission direction of the second laser 109 by rotation.
  • the central controller 107 is connected to the image processor 106 and the rotating table 108 to position the region in which the enrichment of illumination in the treatment subject is located as a tumor region, and controls the rotation of the rotary table 108 to adjust the emission direction of the second laser 109 to the tumor region. .
  • a second laser 109 for emitting laser light to irradiate the tumor region, so that the nano photosensitizer exerts photothermotherapy and/or photodynamic therapy;
  • the central controller 107 is also coupled to the first laser 103 and the second laser 109 for controlling the first laser 103 and the second laser 109 to emit laser light on or off.
  • the central controller 107 can include two control circuits for controlling the activation and deactivation of the first laser 103 and the second laser 109, respectively, and controlling the wavelength and power of the emitted laser light.
  • the wavelength and power of the laser light emitted by the first laser 103 are matched with the nano photosensitizer injected into the body of the treatment object to achieve the purpose of illuminating.
  • the laser light emitted by the first laser 103 has a wavelength in the range of 420-800 nm.
  • the wavelength and power of the laser light emitted by the second laser 109 also need to be matched with the nano photosensitizer injected into the body of the treatment object to achieve the purpose of performing photothermotherapy or photodynamic therapy.
  • the laser light emitted by the second laser 109 has a wavelength in the range of 600 to 1400 nm.
  • the laser nano-optic diagnostic apparatus shown in FIG. 1 may further include an infrared camera, which is composed of an infrared probe, an infrared thermal image processor, and a thermal image display;
  • An infrared probe is disposed in the treatment dark room for receiving infrared rays emitted by the treatment object; and an infrared thermal image processor is connected to the infrared probe for generating a corresponding temperature distribution image according to infrared rays emitted by the treatment object a thermal image display connected to the infrared thermal image processor to display the temperature distribution image.
  • the thermal image display can observe the local or overall temperature of the treated object in real time, which is beneficial to timely adjust the treatment process to improve the therapeutic effect.
  • the laser nano-optical diagnosis and treatment apparatus shown in FIG. 1 may further include an oximeter; the oximeter is composed of a monitoring probe and a data display; wherein the monitoring probe is disposed in the treatment In the dark room, the treatment object is connected for measuring blood oxygen concentration of the tumor area; and a data display is connected to the monitoring probe for displaying blood oxygen concentration data measured by the monitoring probe.
  • the relevant medical personnel can monitor the changes of blood oxygen concentration in the tumor area through the data display, which is beneficial to timely grasping the therapeutic effect and timely adjusting the treatment process and the treatment time.
  • the laser nano-optical diagnostic apparatus shown in FIG. 1 can also provide an illumination source in the treatment darkroom for illuminating the treatment darkroom to facilitate positioning of various instruments in the darkroom. Adjustment, such as aligning the laser to the subject or tumor area.
  • the illumination source may be a circle of LED lights evenly distributed in the treatment darkroom.
  • the embodiment is a specific laser nano-optical diagnosis and treatment device, which comprises: a treatment darkroom 201, a carrying platform 202, a first laser 203, a CCD 204, a filter 205, an image processor 206, and a central control.
  • the instrument includes: a monitoring probe 213 and a data display 214; the illumination source includes: an LED lamp 215.
  • the central controller 207 includes: a first laser control circuit, a second laser control circuit, a rotary table drive circuit, a lighting control circuit, and a CCD control circuit.
  • the first laser control circuit connects the first laser 203 through the optical fiber, and controls the first laser 203 to emit laser light that sets the wave field and power to cause the nano photosensitizer injected into the body of the treatment object to emit light.
  • the second laser control circuit connects the second laser 209 through the optical fiber, and controls the second laser 209 to emit laser light that sets the wave field and power, so that the nano photosensitizer injected into the therapeutic body functions as a photothermal therapy and/or a photodynamic therapy. .
  • the rotary stage drive circuit is coupled to the rotary stage 208 to control the rotation of the rotary stage 208 to adjust the emission direction of the second laser 209.
  • the lighting control circuit connects the illumination source through wires to control the opening and closing of the illumination source.
  • the CCD control circuit connects the CCD 204 through the data line, controls the activation and deactivation of the CCD 204, and transmits the image information captured by the CCD 204 to the image processor 206.
  • the rotary stage drive circuit controls the rotation of the rotary stage 208 in accordance with the processing result of the image processor 206 to cause the second laser 209 to emit laser light in alignment with the tumor area.
  • the laser nano-optical diagnosis and treatment device shown in FIG. 2 is used to perform photothermal treatment on the mouse.
  • the specific operation procedure was as follows: after the mice were anesthetized, 200 ⁇ g/mL of the encapsulated phthalocyanine green phospholipid folate was used to target the nano-photosensitive agent 200 ⁇ L in the tail vein injection, and the anesthetized mice were placed on the carrying platform.
  • the first laser emits a laser of 704 nm, illuminates the mouse, and the corresponding wavelength of the filter is 735 nm.
  • the CCD photographs the mouse; the nano-photosensitive agent determines the tumor area after the tumor reaches maximum enrichment; and the second laser emits 808 nm.
  • the laser was adjusted to a power of 1 W/m 2 and irradiated in the tumor area; the temperature changes of the mouse and the tumor were observed by an infrared camera.
  • a laser nano-optical diagnosis and treatment device as shown in FIG. 2 is used to perform photodynamic therapy on mice.
  • the specific operation procedure was as follows: after the mice were anesthetized, 200 ⁇ g/mL of the encapsulated phthalocyanine green phospholipid folate was used to target the nano-photosensitive agent 200 ⁇ L in the tail vein injection, and the anesthetized mice were placed on the carrying platform.
  • the first laser emits a laser of 704 nm, illuminates the mouse, and the corresponding wavelength of the filter is 735 nm.
  • the CCD photographs the mouse; the nano-photosensitive agent determines the tumor area after the tumor reaches maximum enrichment; and the second laser emits 670 nm.
  • the laser was adjusted to a power of 50 mW/m 2 and irradiated in the tumor area; the blood oxygen concentration of the tumor position of the mouse was observed by an oximeter.
  • the laser nano-optical diagnosis and treatment device emits laser to inject nano-photosensitive agent injected into the treatment object, and monitors the metabolism, distribution and enrichment of the nano photosensitizer in real time, thereby accurately positioning the tumor position through the tumor region.
  • the nano-photosensitive agent emits laser light to enable it to perform photothermal therapy or photodynamic therapy, and achieve non-invasive and non-invasive tumor treatment for the treated subject.

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Abstract

A laser nanometer-scale optical diagnostic device, characterized by comprising: a darkened treatment room (101); a carrying platform (102); a first laser (103) emitting a laser enabling a nanometer-scale photosensitive agent injected in the body of an object of treatment to emit light; a charge coupling image sensing device (CCD) (104) disposed in the darkened treatment room (101); an optical filter (105) disposed between the object of treatment and the CCD (104); an image processor (106) for processing an image captured by the CCD (104), and locating a light concentration region in the body of the object of treatment; a central controller (107) for locating the light concentration region in the body of the object of treatment as a tumor area, and controlling a rotating platform (108) to rotate, the rotating platform (108) being connected to a second laser (109), and adjusting an emitting direction of the second laser (109) via rotation; the second laser (109) disposed on the rotating platform (108), and emitting a laser to enable the nanometer-scale photosensitive agent to exhibit the effects of photo-thermal therapy and/or photodynamic treatment. The device monitors in real time the metabolization, distribution and concentration of the nanometer-scale photosensitive agent, accurately locates a tumor and realizes a noninvasive tumor treatment for an object of treatment.

Description

一种激光纳米光学诊疗设备Laser nano optical diagnosis and treatment equipment
交叉引用cross reference
本申请主张申请日为2014年11月26日,申请号为201410693311.0,发明名称为“一种激光纳米光学诊疗设备”的中国发明专利的优先权。This application claims that the filing date is November 26, 2014, the application number is 201410693311.0, and the invention title is “a laser nano-optical diagnosis and treatment equipment” priority of the Chinese invention patent.
技术领域Technical field
本发明涉及物理诊疗技术领域,具体地,涉及一种激光纳米光学诊疗设备。The present invention relates to the field of physical diagnosis and treatment technology, and in particular to a laser nano-optical diagnosis and treatment device.
背景技术Background technique
传统的手术切除、化疗、放疗或生物治疗已在肿瘤治疗方面取得了非凡的成就,但是其毒副作用、多药耐药等问题仍难以克服。近年来,穿透皮肤的近红外光激活纳米材料的光热、光动力治疗因其存在非侵袭、无毒、靶向、高效等优势而日益受到亲睐。Traditional surgical resection, chemotherapy, radiotherapy or biological therapy have made remarkable achievements in cancer treatment, but its toxic side effects and multi-drug resistance are still difficult to overcome. In recent years, the photothermal and photodynamic therapy of nano-materials that penetrate the skin by near-infrared light has been increasingly favored because of its non-invasive, non-toxic, targeted, and efficient advantages.
光热治疗是指利用各种致热源的热效应,将肿瘤区或全身加热至有效治疗的温度,并维持一定的时间,利用正常组织和肿瘤组织对温度耐受力的差异,达到既能杀灭肿瘤细胞又不损伤正常组织的治疗方法。Photothermal therapy refers to the use of the thermal effects of various pyrogens to heat the tumor area or whole body to the temperature of effective treatment, and maintain a certain time, using the difference in temperature tolerance between normal tissue and tumor tissue, to achieve both killing Tumor cells do not damage the treatment of normal tissues.
光动力疗法是指在光的作用下,利用光敏剂使有机体细胞或生物分子发生机能或形态变化,以达到治疗作用的方法。光动力疗法是完全不同于手术、放疗、化疗和免疫治疗之后的又一种正在研究、快速发展中的崭新疗法,已成为世界肿瘤防治科学中最活跃的研究领域之一。Photodynamic therapy refers to a method in which a photosensitizer is used to cause a functional or morphological change of an organism cell or a biomolecule under the action of light to achieve a therapeutic effect. Photodynamic therapy is another new research that is completely different from surgery, radiotherapy, chemotherapy and immunotherapy. It has become one of the most active research fields in the world of cancer prevention and treatment.
国内外已经在光热、光动力治疗开展了大量的实验;同时新兴的活体动物体内光学成像技术获得革命性的飞跃,已能足了医学伦理学在动物实验方面的要求,将实时光学成像、图像引导治疗已经在肿瘤治疗中显示出独特的优势,但是目前还没有把光热/光动力治疗和活体成像的整合为一体的肿瘤诊疗仪器设备。A large number of experiments have been carried out in photothermal and photodynamic therapy at home and abroad; at the same time, the emerging optical imaging technology of living animals has made a revolutionary leap, which has enabled the requirements of medical ethics in animal experiments, real-time optical imaging, Image-guided therapy has shown unique advantages in cancer therapy, but there is currently no tumor diagnostic equipment that integrates photothermal/photodynamic therapy with in vivo imaging.
发明内容Summary of the invention
本发明实施例的主要目的在于提供一种激光纳米光学诊疗设备,以提供一种将光热治疗技术、光动力治疗技术和活体成像技术集成在一起的诊疗设备。 The main object of the embodiments of the present invention is to provide a laser nano-optical diagnosis and treatment device to provide a diagnosis and treatment device that integrates photothermal therapy technology, photodynamic therapy technology and living body imaging technology.
为了实现上述目的,本发明实施例提供一种激光纳米光学诊疗设备,包括:In order to achieve the above object, an embodiment of the present invention provides a laser nano-optical diagnosis and treatment device, including:
治疗暗室;Treating darkrooms;
承载平台,设置于所述治疗暗室内,用于承载体内注射有纳米光敏剂的治疗对象;a carrying platform disposed in the treatment dark room for carrying a therapeutic object injected with a nano photosensitizer in vivo;
第一激光器,设置于所述治疗暗室内,用于发射激光照射所述治疗对象,使注入所述治疗对象体内的纳米光敏剂发光;a first laser disposed in the treatment dark chamber for emitting laser light to illuminate the treatment object, causing the nano photosensitizer injected into the body of the treatment object to emit light;
电荷耦合图像传感器CCD,设置于所述治疗暗室内;a charge coupled image sensor CCD disposed in the treatment darkroom;
滤光片,设置于所述治疗对象与所述CCD之间,用于滤除设定光谱的光,使所述纳米光敏剂发出的光透过;a filter disposed between the treatment target and the CCD for filtering light of a set spectrum to transmit light emitted by the nano photosensitizer;
所述CCD,用于透过所述滤光片拍摄所述治疗对象;The CCD is configured to photograph the treatment object through the filter;
图像处理器,连接所述CCD,用于获取所述CCD拍摄到的影像,并对所述影像进行图像处理,定位所述治疗对象体内富集发光的区域;An image processor, connected to the CCD, for acquiring an image captured by the CCD, and performing image processing on the image to locate an area enriched in the body of the treatment object;
旋转台,设置于所述治疗暗室内;a rotary table disposed in the treatment darkroom;
第二激光器,装设于所述旋转台上;a second laser mounted on the rotating table;
所述旋转台通过旋转来调整第二激光器的发射方向;The rotating table adjusts a transmitting direction of the second laser by rotating;
中央控制器,连接所述图像处理器和所述旋转台,将所述治疗对象体内富集发光的区域定位为肿瘤区域,并控制所述旋转台旋转以调整第二激光器的发射方向对准所述肿瘤区域;a central controller that connects the image processor and the rotating table, positions an area in which the illumination object is enriched in the treatment object as a tumor area, and controls rotation of the rotating table to adjust an emission direction alignment of the second laser Tumor area;
所述第二激光器用于发射激光照射所述肿瘤区域,使所述纳米光敏剂发挥光热治疗作用和/或光动力治疗作用;The second laser is configured to emit laser light to illuminate the tumor region, so that the nano photosensitizer exerts photothermotherapy and/or photodynamic therapy;
所述中央控制器,还连接所述第一激光器和所述第二激光器,用于控制所述第一激光器和所述第二激光器启动或关闭。The central controller is further connected to the first laser and the second laser for controlling the first laser and the second laser to be turned on or off.
借助于上述技术方案,本发明提供的激光纳米光学诊疗设备通过发射激光使注入治疗对象体内的纳米光敏剂发光,并对纳米光敏剂的代谢、分布和富集进行实时监控,从而准确定位肿瘤的位置,通过对肿瘤区域的纳米光敏剂发射激光使其发挥光热治疗作用或光动力治疗作用,实现对治疗对象进行非侵袭、无创的肿瘤治疗。By means of the above technical solution, the laser nano-optical diagnosis and treatment device provided by the invention emits laser to inject nano-photosensitive agent injected into the treatment object, and monitors the metabolism, distribution and enrichment of the nano photosensitizer in real time, thereby accurately positioning the tumor. The position is achieved by non-invasive and non-invasive tumor treatment of the treated subject by emitting laser light to the nano-photosensitive agent in the tumor region to perform photothermal therapy or photodynamic therapy.
附图说明DRAWINGS
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些 实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments will be briefly described below. It is obvious that the drawings in the following description are only the present invention. Some For the embodiments, those skilled in the art can obtain other drawings according to the drawings without any creative work.
图1是本发明提供的激光纳米光学诊疗设备的结构示意图;1 is a schematic structural view of a laser nano-optical diagnosis and treatment device provided by the present invention;
图2是本发明实施例一提供的激光纳米光学诊疗设备的结构示意图。2 is a schematic structural view of a laser nano-optical diagnosis and treatment device according to Embodiment 1 of the present invention.
具体实施方式detailed description
下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。The technical solutions in the embodiments of the present invention are clearly and completely described in the following with reference to the accompanying drawings in the embodiments of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, but not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts are within the scope of the present invention.
需要说明的是,本发明使用的纳米光敏剂为以磷脂、磷脂聚合物、聚多糖、聚多肽、白蛋白等生物相容性大分子为原料,表面修饰叶酸、Her2等配体,包载吲哚菁绿、IR780、卟啉、纳米金等光敏剂,制备可降解的纳米光敏剂,可实现对肿瘤的靶向识别和富集,并且具有荧光稳定性好、毒副作用低的优点。It should be noted that the nano photosensitizer used in the present invention is a biocompatible macromolecule such as phospholipid, phospholipid polymer, polypolysaccharide, polypeptide, albumin, etc., and surface-modified folic acid, Her2 ligand, etc. Photosensitive agents such as phthalocyanine green, IR780, porphyrin and nano gold can prepare degradable nano photosensitizers, which can achieve targeted recognition and enrichment of tumors, and have the advantages of good fluorescence stability and low toxicity.
以下是本发明使用的一种纳米光敏剂的制备方法:将吲哚菁绿、大豆卵磷脂和二硬脂酰磷脂酰乙醇胺-聚乙二醇-叶酸,按质量比1:1.7:1.7溶于有机溶剂中,旋蒸除去有机溶剂,得到膜状材料。加入2.5mL超纯水,采用超声破碎仪超声5min,采用超滤膜超滤洗涤3次,即得包载吲哚菁绿磷脂叶酸靶向纳米光敏剂。The following is a preparation method of a nano photosensitizer used in the present invention: dissolving phthalocyanine green, soybean lecithin and distearyl phosphatidylethanolamine-polyethylene glycol-folic acid in a mass ratio of 1:1.7:1.7 The organic solvent was removed by rotary evaporation in an organic solvent to obtain a film material. 2.5mL ultrapure water was added, ultrasonicated by ultrasonic sonicator for 5min, and ultrafiltered by ultrafiltration for 3 times, which resulted in the inclusion of phthalocyanine green phospholipid folic acid targeting nano photosensitizer.
本发明提供一种激光纳米光学诊疗设备,如图1所示,该设备包括:治疗暗室101、承载平台102、第一激光器103、电荷耦合图像传感器CCD(Charge-coupled Device)104、滤光片105、图像处理器106、中央控制器107、旋转台108、第二激光器109。The invention provides a laser nano-optical diagnosis and treatment device. As shown in FIG. 1 , the device comprises: a treatment darkroom 101, a carrying platform 102, a first laser 103, a charge-coupled image sensor CCD (Charge-coupled Device) 104, and a filter. 105. Image processor 106, central controller 107, rotating stage 108, and second laser 109.
具体实施时,治疗暗室101可以是由塑料、金属、木材或石材制成。In a specific implementation, the treatment darkroom 101 may be made of plastic, metal, wood or stone.
承载平台102,设置于治疗暗室101中,用于承载体内注射有纳米光敏剂的治疗对象。The carrying platform 102 is disposed in the treatment dark room 101 for carrying a therapeutic object injected with a nano photosensitizer in vivo.
第一激光器103,设置于治疗暗室101内,用于发射激光照射治疗对象,使注入治疗对象体内的纳米光敏剂发光。The first laser 103 is disposed in the treatment dark room 101 for emitting laser irradiation to the treatment subject to illuminate the nano photosensitizer injected into the treatment subject.
CCD104,设置于治疗暗室101内。The CCD 104 is disposed in the treatment dark room 101.
滤光片105,设置于治疗对象与CCD104之间,用于滤除设定光谱的光,使纳米光敏剂发出的光透过。 The filter 105 is disposed between the treatment target and the CCD 104 for filtering out the light of the set spectrum to transmit the light emitted by the nano photosensitizer.
本发明中,滤光片105能够达到滤除杂光的目的,提高根据纳米光敏剂发出的光定位肿瘤位置的准确率。具体实施时,滤光片105需要配合注入治疗对象体内的纳米光敏剂,以达到透过纳米光敏剂发出的光并滤除杂光的目的。In the present invention, the filter 105 can achieve the purpose of filtering out stray light and improve the accuracy of positioning the tumor according to the light emitted by the nano photosensitizer. In a specific implementation, the filter 105 needs to cooperate with the nano photosensitizer injected into the body of the treatment object to achieve the purpose of transmitting the light emitted by the nano photosensitizer and filtering out the stray light.
CCD104,用于透过滤光片105拍摄治疗对象。The CCD 104 is configured to photograph the treatment subject through the filter 105.
图像处理器106,连接CCD104,用于获取CCD104拍摄到的影像,并对影像进行图像处理,定位治疗对象体内富集发光的区域。The image processor 106 is connected to the CCD 104 for acquiring an image captured by the CCD 104, and performing image processing on the image to locate an area enriched in the body of the treatment object.
具体实施时,纳米光敏剂可实现对肿瘤的靶向识别和富集,因此治疗对象的影像中富集发光的区域即为肿瘤区域。In a specific implementation, the nano photosensitizer can achieve targeted recognition and enrichment of the tumor, and thus the region enriched in the luminescence in the image of the treated subject is the tumor region.
旋转台108,设置于治疗暗室101内;第二激光器109,装设于旋转台108上;旋转台108通过旋转来调整第二激光器109的发射方向。The rotary table 108 is disposed in the treatment dark room 101; the second laser 109 is mounted on the rotary table 108; and the rotary table 108 adjusts the emission direction of the second laser 109 by rotation.
中央控制器107,连接图像处理器106和旋转台108,将治疗对象体内富集发光的区域定位为肿瘤区域,并控制旋转台108旋转以调整第二激光器109的发射方向对准所述肿瘤区域。The central controller 107 is connected to the image processor 106 and the rotating table 108 to position the region in which the enrichment of illumination in the treatment subject is located as a tumor region, and controls the rotation of the rotary table 108 to adjust the emission direction of the second laser 109 to the tumor region. .
第二激光器109,用于发射激光照射肿瘤区域,使纳米光敏剂发挥光热治疗作用和/或光动力治疗作用;a second laser 109 for emitting laser light to irradiate the tumor region, so that the nano photosensitizer exerts photothermotherapy and/or photodynamic therapy;
中央控制器107,还连接第一激光器103和第二激光器109,用于控制第一激光器103和第二激光器109发射激光启动或关闭。The central controller 107 is also coupled to the first laser 103 and the second laser 109 for controlling the first laser 103 and the second laser 109 to emit laser light on or off.
具体的,中央控制器107可包括两个控制电路,分别用于控制第一激光器103和第二激光器109的启动、关闭,以及控制所发射激光的波长和功率。Specifically, the central controller 107 can include two control circuits for controlling the activation and deactivation of the first laser 103 and the second laser 109, respectively, and controlling the wavelength and power of the emitted laser light.
具体来说,第一激光器103所发射的激光的波长和功率需配合注入治疗对象体内的纳米光敏剂,以达到使其发光的目的。较佳的,第一激光器103所发射的激光的波长范围为420-800纳米。Specifically, the wavelength and power of the laser light emitted by the first laser 103 are matched with the nano photosensitizer injected into the body of the treatment object to achieve the purpose of illuminating. Preferably, the laser light emitted by the first laser 103 has a wavelength in the range of 420-800 nm.
具体来说,第二激光器109所发射的激光的波长和功率也需配合注入治疗对象体内的纳米光敏剂,以达到使其发挥光热治疗作用或光动力治疗作用的目的。较佳的,第二激光器109所发射的激光的波长范围为600~1400纳米。Specifically, the wavelength and power of the laser light emitted by the second laser 109 also need to be matched with the nano photosensitizer injected into the body of the treatment object to achieve the purpose of performing photothermotherapy or photodynamic therapy. Preferably, the laser light emitted by the second laser 109 has a wavelength in the range of 600 to 1400 nm.
在一种较佳的实施例中,图1所示的激光纳米光学诊疗设备还可以包括一红外热像仪,该红外热像仪由红外探头、红外热像处理器和热像显示器组成;其中,红外探头设置于所述治疗暗室内,用于接收所述治疗对象发出的红外线;红外热像处理器,连接所述红外探头,用于根据所述治疗对象发出的红外线生成相应的温度分布图像;热像显示器,连接所述红外热像处理器,显示所述温度分布图像。这样,相关医疗人员即可通过 热像显示器实时观测治疗对象的局部或整体温度,有利于及时调整治疗过程,以提升治疗疗效。In a preferred embodiment, the laser nano-optic diagnostic apparatus shown in FIG. 1 may further include an infrared camera, which is composed of an infrared probe, an infrared thermal image processor, and a thermal image display; An infrared probe is disposed in the treatment dark room for receiving infrared rays emitted by the treatment object; and an infrared thermal image processor is connected to the infrared probe for generating a corresponding temperature distribution image according to infrared rays emitted by the treatment object a thermal image display connected to the infrared thermal image processor to display the temperature distribution image. In this way, the relevant medical personnel can pass The thermal image display can observe the local or overall temperature of the treated object in real time, which is beneficial to timely adjust the treatment process to improve the therapeutic effect.
在另一种较佳的实施例中,图1所示的激光纳米光学诊疗设备还可以包括血氧仪;该血氧仪由监测探头和数据显示器组成;其中,监测探头,设置于所述治疗暗室内,连接所述治疗对象,用于测量所述肿瘤区域的血氧浓度;数据显示器,连接所述监测探头,用于显示所述监测探头测量得到的血氧浓度数据。这样,相关医疗人员即可通过数据显示器监控肿瘤区域的血氧浓度变化,有利于及时掌握治疗疗效,适时地调整治疗过程和治疗时间。In another preferred embodiment, the laser nano-optical diagnosis and treatment apparatus shown in FIG. 1 may further include an oximeter; the oximeter is composed of a monitoring probe and a data display; wherein the monitoring probe is disposed in the treatment In the dark room, the treatment object is connected for measuring blood oxygen concentration of the tumor area; and a data display is connected to the monitoring probe for displaying blood oxygen concentration data measured by the monitoring probe. In this way, the relevant medical personnel can monitor the changes of blood oxygen concentration in the tumor area through the data display, which is beneficial to timely grasping the therapeutic effect and timely adjusting the treatment process and the treatment time.
在一种较佳的实施例中,图1所示的激光纳米光学诊疗设备还可以在治疗暗室中设置照明光源,用于对所述治疗暗室照明,以便于对暗室内的各种仪器进行位置调整,如使激光器对准治疗对象或肿瘤区域。In a preferred embodiment, the laser nano-optical diagnostic apparatus shown in FIG. 1 can also provide an illumination source in the treatment darkroom for illuminating the treatment darkroom to facilitate positioning of various instruments in the darkroom. Adjustment, such as aligning the laser to the subject or tumor area.
具体实施时,照明光源可以是均布于治疗暗室内的一圈LED灯。In a specific implementation, the illumination source may be a circle of LED lights evenly distributed in the treatment darkroom.
实施例一Embodiment 1
如图2所示,本实施例为一具体的激光纳米光学诊疗设备,该设备包括:治疗暗室201、承载平台202、第一激光器203、CCD204、滤光片205、图像处理器206、中央控制器207、旋转台208、第二激光器209、红外热像仪、血氧仪、照明光源;其中,红外热像仪包括:红外探头210、红外热像处理器211和热像显示器212;血氧仪包括:监测探头213和数据显示器214;照明光源包括:LED灯215。As shown in FIG. 2, the embodiment is a specific laser nano-optical diagnosis and treatment device, which comprises: a treatment darkroom 201, a carrying platform 202, a first laser 203, a CCD 204, a filter 205, an image processor 206, and a central control. The 207, the rotating 208, the second laser 209, the infrared camera, the oximeter, the illumination source; wherein, the infrared camera comprises: an infrared probe 210, an infrared thermal image processor 211 and a thermal image display 212; The instrument includes: a monitoring probe 213 and a data display 214; the illumination source includes: an LED lamp 215.
其中,中央控制器207包括:第一激光器控制电路、第二激光器控制电路、旋转台驱动电路、照明控制电路、CCD控制电路。The central controller 207 includes: a first laser control circuit, a second laser control circuit, a rotary table drive circuit, a lighting control circuit, and a CCD control circuit.
第一激光器控制电路通过光纤连接第一激光器203,控制第一激光器203发射设定波场和功率的激光,以使注入治疗对象体内的纳米光敏剂发光。The first laser control circuit connects the first laser 203 through the optical fiber, and controls the first laser 203 to emit laser light that sets the wave field and power to cause the nano photosensitizer injected into the body of the treatment object to emit light.
第二激光器控制电路通过光纤连接第二激光器209,控制第二激光器209发射设定波场和功率的激光,以使注入治疗对象体内的纳米光敏剂发挥光热治疗作用和/或光动力治疗作用。The second laser control circuit connects the second laser 209 through the optical fiber, and controls the second laser 209 to emit laser light that sets the wave field and power, so that the nano photosensitizer injected into the therapeutic body functions as a photothermal therapy and/or a photodynamic therapy. .
旋转台驱动电路连接旋转台208,控制旋转台208旋转,以调整第二激光器209的发射方向。The rotary stage drive circuit is coupled to the rotary stage 208 to control the rotation of the rotary stage 208 to adjust the emission direction of the second laser 209.
照明控制电路通过导线连接照明光源,控制照明光源的开与闭。The lighting control circuit connects the illumination source through wires to control the opening and closing of the illumination source.
CCD控制电路通过数据线连接CCD204,控制CCD204的启动与关闭,并将CCD204拍摄的影像信息并传输给图像处理器206。 The CCD control circuit connects the CCD 204 through the data line, controls the activation and deactivation of the CCD 204, and transmits the image information captured by the CCD 204 to the image processor 206.
旋转台驱动电路根据图像处理器206的处理结果,控制旋转台208旋转,以使第二激光器209对准肿瘤区域发射激光。The rotary stage drive circuit controls the rotation of the rotary stage 208 in accordance with the processing result of the image processor 206 to cause the second laser 209 to emit laser light in alignment with the tumor area.
实施例二Embodiment 2
本实施例为采用如图2所示的激光纳米光学诊疗设备,对小白鼠进行光热治疗。In this embodiment, the laser nano-optical diagnosis and treatment device shown in FIG. 2 is used to perform photothermal treatment on the mouse.
具体操作过程为:小白鼠麻醉后,尾静脉注射内注入200μg/mL的包载吲哚菁绿磷脂叶酸靶向纳米光敏剂200μL,将麻醉小白鼠置于承载平台上。第一激光器发出704nm的激光,照射小白鼠,滤光片对应波长为735nm,CCD对小白鼠进行拍摄;纳米光敏剂在肿瘤达到最大富集后,确定出肿瘤区域;打开第二激光器发射808nm的激光,调节功率为1W/m2,照射在肿瘤区域;通过红外热像仪观测小白鼠及肿瘤位置的温度变化。The specific operation procedure was as follows: after the mice were anesthetized, 200 μg/mL of the encapsulated phthalocyanine green phospholipid folate was used to target the nano-photosensitive agent 200 μL in the tail vein injection, and the anesthetized mice were placed on the carrying platform. The first laser emits a laser of 704 nm, illuminates the mouse, and the corresponding wavelength of the filter is 735 nm. The CCD photographs the mouse; the nano-photosensitive agent determines the tumor area after the tumor reaches maximum enrichment; and the second laser emits 808 nm. The laser was adjusted to a power of 1 W/m 2 and irradiated in the tumor area; the temperature changes of the mouse and the tumor were observed by an infrared camera.
实施例三Embodiment 3
本实施例为采用如图2所示的激光纳米光学诊疗设备,对小白鼠进行光动力治疗。In this embodiment, a laser nano-optical diagnosis and treatment device as shown in FIG. 2 is used to perform photodynamic therapy on mice.
具体操作过程为:小白鼠麻醉后,尾静脉注射内注入200μg/mL的包载吲哚菁绿磷脂叶酸靶向纳米光敏剂200μL,将麻醉小白鼠置于承载平台上。第一激光器发出704nm的激光,照射小白鼠,滤光片对应波长为735nm,CCD对小白鼠进行拍摄;纳米光敏剂在肿瘤达到最大富集后,确定出肿瘤区域;打开第二激光器发射670nm的激光,调节功率为50mW/m2,照射在肿瘤区域;通过血氧仪观测小白鼠肿瘤位置的血氧浓度变化。The specific operation procedure was as follows: after the mice were anesthetized, 200 μg/mL of the encapsulated phthalocyanine green phospholipid folate was used to target the nano-photosensitive agent 200 μL in the tail vein injection, and the anesthetized mice were placed on the carrying platform. The first laser emits a laser of 704 nm, illuminates the mouse, and the corresponding wavelength of the filter is 735 nm. The CCD photographs the mouse; the nano-photosensitive agent determines the tumor area after the tumor reaches maximum enrichment; and the second laser emits 670 nm. The laser was adjusted to a power of 50 mW/m 2 and irradiated in the tumor area; the blood oxygen concentration of the tumor position of the mouse was observed by an oximeter.
本发明提供的激光纳米光学诊疗设备通过发射激光使注入治疗对象体内的纳米光敏剂发光,并对纳米光敏剂的代谢、分布和富集进行实时监控,从而准确定位肿瘤的位置,通过对肿瘤区域的纳米光敏剂发射激光使其发挥光热治疗作用或光动力治疗作用,实现对治疗对象进行非侵袭、无创的肿瘤治疗。The laser nano-optical diagnosis and treatment device provided by the invention emits laser to inject nano-photosensitive agent injected into the treatment object, and monitors the metabolism, distribution and enrichment of the nano photosensitizer in real time, thereby accurately positioning the tumor position through the tumor region. The nano-photosensitive agent emits laser light to enable it to perform photothermal therapy or photodynamic therapy, and achieve non-invasive and non-invasive tumor treatment for the treated subject.
以上所述的具体实施例,对本发明的目的、技术方案和有益效果进行了进一步详细说明,所应理解的是,以上所述仅为本发明的具体实施例而已,并不用于限定本发明的保护范围,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。 The above described specific embodiments of the present invention are further described in detail, and are intended to be illustrative of the embodiments of the present invention. All modifications, equivalent substitutions, improvements, etc., made within the spirit and scope of the invention are intended to be included within the scope of the invention.

Claims (6)

  1. 一种激光纳米光学诊疗设备,其特征在于,包括:A laser nano-optical diagnosis and treatment device, comprising:
    治疗暗室;Treating darkrooms;
    承载平台,设置于所述治疗暗室内,用于承载体内注射有纳米光敏剂的治疗对象;a carrying platform disposed in the treatment dark room for carrying a therapeutic object injected with a nano photosensitizer in vivo;
    第一激光器,设置于所述治疗暗室内,用于发射激光照射所述治疗对象,使注入所述治疗对象体内的纳米光敏剂发光;a first laser disposed in the treatment dark chamber for emitting laser light to illuminate the treatment object, causing the nano photosensitizer injected into the body of the treatment object to emit light;
    电荷耦合图像传感器CCD,设置于所述治疗暗室内;a charge coupled image sensor CCD disposed in the treatment darkroom;
    滤光片,设置于所述治疗对象与所述CCD之间,用于滤除设定光谱的光,使所述纳米光敏剂发出的光透过;a filter disposed between the treatment target and the CCD for filtering light of a set spectrum to transmit light emitted by the nano photosensitizer;
    所述CCD,用于透过所述滤光片拍摄所述治疗对象;The CCD is configured to photograph the treatment object through the filter;
    图像处理器,连接所述CCD,用于获取所述CCD拍摄到的影像,并对所述影像进行图像处理,定位所述治疗对象体内富集发光的区域;An image processor, connected to the CCD, for acquiring an image captured by the CCD, and performing image processing on the image to locate an area enriched in the body of the treatment object;
    旋转台,设置于所述治疗暗室内;a rotary table disposed in the treatment darkroom;
    第二激光器,装设于所述旋转台上;a second laser mounted on the rotating table;
    所述旋转台通过旋转来调整第二激光器的发射方向;The rotating table adjusts a transmitting direction of the second laser by rotating;
    中央控制器,连接所述图像处理器和所述旋转台,将所述治疗对象体内富集发光的区域定位为肿瘤区域,并控制所述旋转台旋转以调整第二激光器的发射方向对准所述肿瘤区域;a central controller that connects the image processor and the rotating table, positions an area in which the illumination object is enriched in the treatment object as a tumor area, and controls rotation of the rotating table to adjust an emission direction alignment of the second laser Tumor area;
    所述第二激光器用于发射激光照射所述肿瘤区域,使所述纳米光敏剂发挥光热治疗作用和/或光动力治疗作用;The second laser is configured to emit laser light to illuminate the tumor region, so that the nano photosensitizer exerts photothermotherapy and/or photodynamic therapy;
    所述中央控制器,还连接所述第一激光器和所述第二激光器,用于控制所述第一激光器和所述第二激光器启动或关闭。The central controller is further connected to the first laser and the second laser for controlling the first laser and the second laser to be turned on or off.
  2. 根据权利要求1所述的激光纳米光学诊疗设备,其特征在于,还包括:红外热像仪;The laser nano-optical diagnosis and treatment apparatus according to claim 1, further comprising: an infrared camera;
    所述红外热像仪包括:红外探头、红外热像处理器和热像显示器;The infrared camera includes: an infrared probe, an infrared thermal image processor, and a thermal image display;
    所述红外探头,设置于所述治疗暗室内,用于接收所述治疗对象发出的红外线;The infrared probe is disposed in the treatment dark room for receiving infrared rays emitted by the treatment object;
    红外热像处理器,连接所述红外探头,用于根据所述治疗对象发出的红外线生成相应的温度分布图像;An infrared thermal image processor, connected to the infrared probe, for generating a corresponding temperature distribution image according to infrared rays emitted by the treatment object;
    热像显示器,连接所述红外热像处理器,显示所述温度分布图像。A thermal image display is coupled to the infrared thermal image processor to display the temperature distribution image.
  3. 根据权利要求1所述的激光纳米光学诊疗设备,其特征在于,还包括:血氧仪; The laser nano-optical diagnosis and treatment apparatus according to claim 1, further comprising: an oximeter;
    所述血氧仪包括:监测探头、数据显示器;The oximeter includes: a monitoring probe and a data display;
    所述监测探头,设置于所述治疗暗室内,连接所述治疗对象,用于测量所述肿瘤区域的血氧浓度;The monitoring probe is disposed in the treatment dark chamber and connected to the treatment object for measuring blood oxygen concentration of the tumor region;
    所述数据显示器,连接所述监测探头,用于显示所述监测探头测量得到的血氧浓度数据。The data display is connected to the monitoring probe for displaying blood oxygen concentration data measured by the monitoring probe.
  4. 根据权利要求1所述的激光纳米光学诊疗设备,其特征在于,还包括:The laser nano-optical diagnosis and treatment device according to claim 1, further comprising:
    照明光源,设置于所述治疗暗室中,用于对所述治疗暗室照明。An illumination source disposed in the treatment darkroom for illuminating the treatment darkroom.
  5. 根据权利要求1所述的激光纳米光学诊疗设备,其特征在于,The laser nano-optical diagnosis and treatment apparatus according to claim 1, wherein
    所述第一激光器发射的激光波长范围是420-800纳米。The first laser emits a laser having a wavelength in the range of 420-800 nm.
  6. 根据权利要求1所述的激光纳米光学诊疗设备,其特征在于,The laser nano-optical diagnosis and treatment apparatus according to claim 1, wherein
    所述第二激光器发射的激光的波长范围为600~1400纳米。 The laser light emitted by the second laser has a wavelength in the range of 600 to 1400 nm.
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