CN118592899A - In vivo skin optical detection device - Google Patents
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Abstract
本申请涉及皮肤微区结构成像技术领域,提供一种在体皮肤光学检测装置,包括表皮成像模组、共聚焦显微模组及拉曼散射模组,其中,表皮成像模组用于获取待测皮肤目标区域的表皮原始图像,共聚焦显微模组用于获取待测皮肤目标区域的三维结构信息,拉曼散射模组用于获取待测皮肤目标区域的三维成分信息,可以看出,上述在体皮肤光学检测装置通过表皮成像模组、共聚焦显微模组及拉曼散射模组协同配合即实现对皮肤三维结构信息及三维成分信息的非侵入式检测,避免进行皮肤活体切片存在的失去活性以及引入医源性损伤的风险。
The present application relates to the technical field of skin micro-region structure imaging, and provides an in vivo skin optical detection device, including an epidermal imaging module, a confocal microscopy module and a Raman scattering module, wherein the epidermal imaging module is used to obtain an original image of the epidermis of a target skin area to be measured, the confocal microscopy module is used to obtain three-dimensional structural information of the target skin area to be measured, and the Raman scattering module is used to obtain three-dimensional component information of the target skin area to be measured. It can be seen that the above-mentioned in vivo skin optical detection device realizes non-invasive detection of three-dimensional structural information and three-dimensional component information of the skin through the coordinated cooperation of the epidermal imaging module, the confocal microscopy module and the Raman scattering module, thereby avoiding the risk of loss of activity and introduction of iatrogenic damage in performing live skin sections.
Description
技术领域Technical Field
本申请属于皮肤微区结构成像技术领域,更具体地说,是涉及一种在体皮肤光学检测装置。The present application belongs to the technical field of skin micro-region structure imaging, and more specifically, to an in-vivo skin optical detection device.
背景技术Background Art
皮肤是指披覆在人体的表层,直接与外界环境相接触的生物组织,其具有相对复杂的形态结构及组成成分,为了深入了解皮肤的生理机制及病理机制,进而实现医学筛查、疾病治疗及相关研究等目的,此前,医学领域常用的检测方法是进行皮肤活体切片,随即通过检测仪器获取皮肤的结构信息及成分信息,但是上述检测方法存在失去活性以及引入医源性损伤的风险,导致在实际应用中存在限制。Skin refers to the biological tissue that covers the surface of the human body and is in direct contact with the external environment. It has a relatively complex morphological structure and composition. In order to gain a deeper understanding of the physiological and pathological mechanisms of the skin, and thereby achieve the purposes of medical screening, disease treatment, and related research, the commonly used detection method in the medical field was to perform a live skin slice and then obtain the structural and composition information of the skin through a detection instrument. However, the above detection method has the risk of losing activity and introducing iatrogenic damage, which leads to limitations in practical applications.
发明内容Summary of the invention
本申请的目的在于提供一种在体皮肤光学检测装置,旨在解决目前通过切片检测皮肤的结构信息及成分信息时,存在失去活性以及引入医源性损伤的风险,导致在实际应用中存在限制的问题。The purpose of the present application is to provide an in vivo skin optical detection device, which aims to solve the problem that when the structural information and composition information of the skin is currently detected through slices, there is a risk of loss of activity and introduction of iatrogenic damage, which leads to limitations in practical applications.
为实现上述目的,提供一种在体皮肤光学检测装置,包括表皮成像模组、共聚焦显微模组及拉曼散射模组,所述表皮成像模组、所述共聚焦显微模组以及所述拉曼散射模组共用部分光路结构,表皮成像模组用于获取待测皮肤目标区域的表皮原始图像,共聚焦显微模组用于获取待测皮肤目标区域的三维结构信息,拉曼散射模组用于获取待测皮肤目标区域的三维成分信息。To achieve the above-mentioned purpose, an in vivo skin optical detection device is provided, comprising an epidermal imaging module, a confocal microscopy module and a Raman scattering module. The epidermal imaging module, the confocal microscopy module and the Raman scattering module share a part of the optical path structure. The epidermal imaging module is used to obtain an original image of the epidermis of a target skin area to be measured, the confocal microscopy module is used to obtain three-dimensional structural information of the target skin area to be measured, and the Raman scattering module is used to obtain three-dimensional composition information of the target skin area to be measured.
在其中一个实施例中,表皮成像模组包括科勒照明模块、第一分光棱镜、物镜模块、扫描透镜-管镜镜组、第一透镜及第一成像模块;In one embodiment, the epidermal imaging module includes a Kohler illumination module, a first beam splitter prism, an objective lens module, a scanning lens-tube lens assembly, a first lens, and a first imaging module;
科勒照明模块用于发射照明光线,照明光线依次经由第一分光棱镜反射、物镜模块聚焦后入射至待测皮肤目标区域并生成反射光线,反射光线依次经由物镜模块透射、第一分光棱镜透射、扫描透镜-管镜镜组透射、第一透镜聚焦后入射至第一成像模块生成待测皮肤目标区域的表皮原始图像。The Kohler illumination module is used to emit illumination light, which is reflected by the first beam splitter prism in sequence, focused by the objective lens module, and then incident on the target skin area to be measured to generate reflected light, which is transmitted by the objective lens module, the first beam splitter prism, the scanning lens-tube lens group, and focused by the first lens before being incident on the first imaging module to generate an original image of the epidermis of the target skin area to be measured.
在其中一个实施例中,表皮成像模组、共聚焦显微模组以及拉曼散射模组共用的部分光路结构至少包括所第一分光棱镜、所物镜模块以及扫描透镜-管镜镜组。In one embodiment, the partial optical path structure shared by the epidermal imaging module, the confocal microscopy module and the Raman scattering module at least includes the first beam splitter prism, the objective lens module and the scanning lens-tube lens assembly.
在其中一个实施例中,物镜模块包括固定镜筒及沿固定镜筒轴向活动设置于固定镜筒内的物镜主体,固定镜筒两端开口且用于朝向待测皮肤目标区域的一端设有封闭相应开口的蓝宝石透光镜片;In one embodiment, the objective lens module includes a fixed lens barrel and an objective lens body movably disposed in the fixed lens barrel along the axial direction of the fixed lens barrel, and the fixed lens barrel has two openings at both ends and one end facing the target skin area to be measured is provided with a sapphire light-transmitting lens that closes the corresponding opening;
相应照明光线依次经由第一分光棱镜反射、物镜主体聚焦、蓝宝石透光镜片透射后入射至待测皮肤目标区域,反射光线依次经由蓝宝石透光镜片透射,物镜主体透射、第一分光棱镜透射、扫描透镜-管镜镜组透射、第一透镜聚焦后入射至第一成像模块生成待测皮肤目标区域的表皮原始图像。The corresponding illumination light is sequentially reflected by the first beam splitter prism, focused by the objective lens body, and transmitted through the sapphire light-transmitting lens before entering the target skin area to be measured. The reflected light is sequentially transmitted through the sapphire light-transmitting lens, the objective lens body, the first beam splitter prism, the scanning lens-tube lens group, and focused by the first lens before entering the first imaging module to generate an original epidermal image of the target skin area to be measured.
在其中一个实施例中,共聚焦显微模组包括激光光源模块,中性密度滤光片、第二透镜、第一共焦针孔结构、第三透镜、偏振分光棱镜、扫描振镜、第二分光棱镜及四分之一波片、第四透镜、第二共焦针孔结构及第二成像模块,且扫描透镜-管镜镜组构成4f光学系统;In one embodiment, the confocal microscopy module includes a laser light source module, a neutral density filter, a second lens, a first confocal pinhole structure, a third lens, a polarization beam splitter prism, a scanning galvanometer, a second beam splitter prism and a quarter wave plate, a fourth lens, a second confocal pinhole structure and a second imaging module, and the scanning lens-tube lens group constitutes a 4f optical system;
激光光源模块用于发射激发光线,激发光线依次经由中性密度滤光片滤光、第二透镜聚焦、第一共焦针孔结构滤光、第三透镜准直、偏振分光棱镜垂直偏振、扫描振镜反射、第二分光棱镜透射、扫描透镜-管镜镜组透射、四分之一波片、第一分光棱镜透射、物镜主体聚焦、蓝宝石透光镜片透射后入射至待测皮肤目标区域生成散射光线,散射光线依次经由蓝宝石透光镜片透射,物镜主体透射、第一分光棱镜透射、四分之一波片偏振、扫描透镜-管镜镜组透射,第二分光棱镜透射、扫描振镜反射、偏振分光棱镜透射、第四透镜聚焦、第二共焦针孔结构滤光后入射至第二成像模块生成待测皮肤目标区域的三维结构信息;The laser light source module is used to emit excitation light, which is sequentially filtered by a neutral density filter, focused by a second lens, filtered by a first confocal pinhole structure, collimated by a third lens, vertically polarized by a polarizing beam splitter prism, reflected by a scanning galvanometer, transmitted by a second beam splitter prism, transmitted by a scanning lens-tube lens group, a quarter wave plate, transmitted by a first beam splitter prism, focused by an objective lens body, and transmitted by a sapphire light-transmitting lens before being incident on a target skin area to be measured to generate scattered light, and the scattered light is sequentially transmitted by a sapphire light-transmitting lens, transmitted by an objective lens body, transmitted by a first beam splitter prism, polarized by a quarter wave plate, transmitted by a scanning lens-tube lens group, transmitted by a second beam splitter prism, reflected by a scanning galvanometer, transmitted by a polarizing beam splitter prism, focused by a fourth lens, and filtered by a second confocal pinhole structure before being incident on a second imaging module to generate three-dimensional structural information of the target skin area to be measured;
相应照明光线依次经由第一分光棱镜反射、物镜主体聚焦、蓝宝石透光镜片透射后入射至待测皮肤目标区域,反射光线依次经由蓝宝石透光镜片透射,物镜主体透射、第一分光棱镜透射、四分之一波片偏振、扫描透镜-管镜镜组透射,第二分光棱镜反射、第一透镜聚焦后入射至第一成像模块生成待测皮肤目标区域的表皮原始图像。The corresponding illumination light is sequentially reflected by the first beam splitter prism, focused by the objective lens body, and transmitted through the sapphire light-transmitting lens before being incident on the target skin area to be measured; the reflected light is sequentially transmitted through the sapphire light-transmitting lens, the objective lens body, the first beam splitter prism, polarized by a quarter-wave plate, and transmitted through the scanning lens-tube lens group; the reflected light is sequentially transmitted through the second beam splitter prism, focused by the first lens, and then incident on the first imaging module to generate an original epidermal image of the target skin area to be measured.
在其中一个实施例中,拉曼散射模组包括第三分光棱镜、长通滤光片、第五透镜、可调狭缝、第一凹面反射镜、光栅、第二凹面反射镜及第三成像模块;In one embodiment, the Raman scattering module includes a third beam splitter prism, a long pass filter, a fifth lens, an adjustable slit, a first concave reflector, a grating, a second concave reflector and a third imaging module;
激光光源模块用于发射激发光线,激发光线依次经由中性密度滤光片滤光、第二透镜聚焦、第一共焦针孔结构滤光、第三透镜准直、偏振分光棱镜垂直偏振、第三分光棱镜透射,扫描振镜反射、第二分光棱镜透射、扫描透镜-管镜镜组透射、四分之一波片偏振、第一分光棱镜透射、物镜主体聚焦、蓝宝石透光镜片透射后入射至待测皮肤目标区域并生成散射光线,散射光线依次经由蓝宝石透光镜片透射,物镜主体透射、第一分光棱镜透射、四分之一波片偏振、扫描透镜-管镜镜组透射,第二分光棱镜透射、扫描振镜反射、第三分光棱镜反射、长通滤光片滤光,第五透镜聚焦、可调狭缝滤光、第一凹面反射镜反射、光栅衍射、第二凹面反射镜反射后入射至第三成像模块生成待测皮肤目标区域的三维成分信息;The laser light source module is used to emit excitation light, which is sequentially filtered by a neutral density filter, focused by a second lens, filtered by a first confocal pinhole structure, collimated by a third lens, vertically polarized by a polarizing beam splitter prism, transmitted by a third beam splitter prism, reflected by a scanning galvanometer, transmitted by a second beam splitter prism, transmitted by a scanning lens-tube lens group, polarized by a quarter wave plate, transmitted by a first beam splitter prism, focused by an objective lens body, and transmitted by a sapphire light-transmitting lens, and then incident on a target skin area to be measured and generates scattered light. The scattered light is sequentially transmitted by a sapphire light-transmitting lens, transmitted by an objective lens body, transmitted by a first beam splitter prism, polarized by a quarter wave plate, transmitted by a scanning lens-tube lens group, transmitted by a second beam splitter prism, reflected by a scanning galvanometer, reflected by a third beam splitter prism, filtered by a long-pass filter, focused by a fifth lens, filtered by an adjustable slit, reflected by a first concave reflector, diffracted by a grating, and reflected by a second concave reflector, and then incident on a third imaging module to generate three-dimensional composition information of the target skin area to be measured;
相应激发光线依次经由中性密度滤光片滤光、第二透镜聚焦、第一共焦针孔结构滤光、第三透镜准直、偏振分光棱镜垂直偏振、第三分光棱镜透射、扫描振镜反射、第二分光棱镜透射、扫描透镜-管镜镜组透射、四分之一波片偏振、第一分光棱镜透射、物镜主体聚焦、蓝宝石透光镜片透射后入射至待测皮肤目标区域,散射光线依次经由蓝宝石透光镜片透射,物镜主体透射、第一分光棱镜透射、四分之一波片片偏振、扫描透镜-管镜镜组透射,第二分光棱镜透射、扫描振镜反射、第三分光棱镜透射、偏振分光棱镜透射、第四透镜聚焦、第二共焦针孔结构滤光后入射至第二成像模块生成待测皮肤目标区域的三维结构信息。The corresponding excitation light is filtered by a neutral density filter, focused by a second lens, filtered by a first confocal pinhole structure, collimated by a third lens, vertically polarized by a polarizing beam splitter prism, transmitted by a third beam splitter prism, reflected by a scanning galvanometer, transmitted by a second beam splitter prism, transmitted by a scanning lens-tube lens group, polarized by a quarter wave plate, transmitted by a first beam splitter prism, focused by an objective lens body, and transmitted by a sapphire light-transmitting lens before being incident on a target skin area to be measured. The scattered light is transmitted by a sapphire light-transmitting lens, transmitted by an objective lens body, transmitted by a first beam splitter prism, polarized by a quarter wave plate, transmitted by a scanning lens-tube lens group, transmitted by a second beam splitter prism, reflected by a scanning galvanometer, transmitted by a third beam splitter prism, transmitted by a polarizing beam splitter prism, focused by a fourth lens, and filtered by a second confocal pinhole structure before being incident on a second imaging module to generate three-dimensional structural information of the target skin area to be measured.
在其中一个实施例中,还包括光路调整模组,光路调整模组包括第一平面反射镜及第二平面反射镜,激发光线经由第三透镜准直后,再经由第一平面反射镜反射至偏振分光棱镜,散射光线经由第三透镜聚焦后,再经由第二平面反射镜反射至第二共焦针孔结构。In one embodiment, an optical path adjustment module is also included, which includes a first plane reflector and a second plane reflector. The excitation light is collimated by a third lens and then reflected by the first plane reflector to the polarization splitter prism. The scattered light is focused by the third lens and then reflected by the second plane reflector to the second confocal pinhole structure.
在其中一个实施例中,激发光线为波长810-850nm的准直光线。In one embodiment, the excitation light is a collimated light with a wavelength of 810-850 nm.
在其中一个实施例中,还包括固定平台及驱动连接固定平台的三轴运动模块。In one embodiment, it also includes a fixed platform and a three-axis motion module drivingly connected to the fixed platform.
本申请提供的在体皮肤光学检测装置的有益效果在于,与现有技术相比,上述在体皮肤光学检测装置包括表皮成像模组、共聚焦显微模组及拉曼散射模组,其中,表皮成像模组用于获取待测皮肤目标区域的表皮原始图像,共聚焦显微模组用于获取待测皮肤目标区域的三维结构信息,拉曼散射模组用于获取待测皮肤目标区域的三维成分信息,可以看出,上述在体皮肤光学检测装置通过表皮成像模组、共聚焦显微模组及拉曼散射模组协同配合即实现对皮肤三维结构信息及三维成分信息的非侵入式检测,避免进行皮肤活体切片存在的失去活性以及引入医源性损伤的风险。The beneficial effect of the in vivo skin optical detection device provided by the present application is that, compared with the prior art, the above-mentioned in vivo skin optical detection device includes an epidermal imaging module, a confocal microscopy module and a Raman scattering module, wherein the epidermal imaging module is used to obtain the original image of the epidermis of the target skin area to be tested, the confocal microscopy module is used to obtain the three-dimensional structural information of the target skin area to be tested, and the Raman scattering module is used to obtain the three-dimensional composition information of the target skin area to be tested. It can be seen that the above-mentioned in vivo skin optical detection device realizes non-invasive detection of the three-dimensional structural information and three-dimensional composition information of the skin through the coordinated cooperation of the epidermal imaging module, the confocal microscopy module and the Raman scattering module, thereby avoiding the risk of loss of activity and introduction of iatrogenic damage in live skin sections.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
为了更清楚地说明本申请实施例中的技术方案,下面将对实施例或现有技术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申请的一些实施例,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 technical solutions in the embodiments of the present application, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
图1为本申请一实施例提供在体皮肤光学检测装置的光路结构示意图;FIG1 is a schematic diagram of the optical path structure of an in-body skin optical detection device according to an embodiment of the present application;
图2为图1所示在体皮肤光学检测装置中表皮成像模组的光路结构示意图;FIG2 is a schematic diagram of the optical path structure of the epidermal imaging module in the in-vivo skin optical detection device shown in FIG1 ;
图3为图1所示在体皮肤光学检测装置中共聚焦显微模组的光路结构示意图;FIG3 is a schematic diagram of the optical path structure of a co-focusing microscopy module in the in vivo skin optical detection device shown in FIG1 ;
图4为图1所示在体皮肤光学检测装置中拉曼散射模组的光路结构示意图;FIG4 is a schematic diagram of the optical path structure of the Raman scattering module in the in-vivo skin optical detection device shown in FIG1 ;
图5为皮肤三维结构信息示意图;FIG5 is a schematic diagram of skin three-dimensional structure information;
图6为皮肤三维成分信息示意图。FIG. 6 is a schematic diagram of three-dimensional skin composition information.
图中:10、在体皮肤光学检测装置;20、待测皮肤目标区域;100、表皮成像模组;110、科勒照明模块;120、第一分光棱镜;130、物镜模块;132、固定镜筒;134、物镜主体;136、蓝宝石透光镜片;140、扫描透镜-管镜镜组;150、第一透镜;160、第一成像模块;200、共聚焦显微模组;210、激光光源模块;220、中性密度滤光片;230、第二透镜;240、第一共焦针孔结构;250、第三透镜;260、偏振分光棱镜;270、扫描振镜;280、第二分光棱镜;290、四分之一波片;292、第四透镜;294、第二共焦针孔结构;296、第二成像模块;300、拉曼散射模组;310、第三分光棱镜;320、长通滤光片;330、第五透镜;340、可调狭缝;350、第一凹面反射镜;360、光栅;370、第二凹面反射镜;380、第三成像模块;400、光路调整模组;410、第一平面反射镜;420、第二平面反射镜。In the figure: 10, in vivo skin optical detection device; 20, target skin area to be tested; 100, epidermal imaging module; 110, Kohler illumination module; 120, first beam splitter prism; 130, objective lens module; 132, fixed lens barrel; 134, objective lens body; 136, sapphire light-transmitting lens; 140, scanning lens-tube lens group; 150, first lens; 160, first imaging module; 200, confocal microscopy module; 210, laser light source module; 220, neutral density filter; 230, second lens; 240, first confocal pinhole structure; 250, third lens; 260, polarization beam splitter prism; 270, scanning galvanometer; 280, second beam splitter prism; 290, quarter wave plate; 292, fourth lens; 294, second confocal pinhole structure; 296, second imaging module; 300, Raman scattering module; 310, third beam splitter prism; 320, long pass filter; 330, fifth lens; 340, adjustable slit; 350, first concave reflector; 360, grating; 370, second concave reflector; 380, third imaging module; 400, optical path adjustment module; 410, first plane reflector; 420, second plane reflector.
具体实施方式DETAILED DESCRIPTION
为了使本申请所要解决的技术问题、技术方案及有益效果更加清楚明白,以下结合附图及实施例,对本申请进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本申请,并不用于限定本申请。In order to make the technical problems, technical solutions and beneficial effects to be solved by this application more clearly understood, this application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain this application and are not used to limit this application.
需要说明的是,当元件被称为“固定于”或“设置于”另一个元件,它可以直接在另一个元件上或者间接在该另一个元件上。当一个元件被称为是“连接于”另一个元件,它可以是直接连接到另一个元件或间接连接至该另一个元件上。It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.
需要理解的是,术语“长度”、“宽度”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本申请和简化描述,而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作,因此不能理解为对本申请的限制。It should be understood that the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.
此外,术语“第一”、“第二”仅用于描述目的,而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此,限定有“第一”、“第二”的特征可以明示或者隐含地包括一个或者更多个该特征。在本申请的描述中,“多个”的含义是两个或两个以上,除非另有明确具体的限定。In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.
皮肤是指披覆在人体的表层,直接与外界环境相接触的生物组织,其具有相对复杂的形态结构及组成成分,为了深入了解皮肤的生理机制及病理机制,进而实现医学筛查、疾病治疗及相关研究等目的,此前,医学领域常用的检测方法是进行皮肤活体切片,随即通过检测仪器获取皮肤的形态信息及成分信息,但是上述检测方法存在失去活性以及引入医源性损伤的风险,导致在实际应用中存在限制。Skin refers to the biological tissue that covers the surface of the human body and is in direct contact with the external environment. It has a relatively complex morphological structure and components. In order to gain a deeper understanding of the physiological and pathological mechanisms of the skin, and thereby achieve the purposes of medical screening, disease treatment, and related research, previously, the commonly used detection method in the medical field was to perform a live skin slice, and then obtain the skin's morphological and composition information through a detection instrument. However, the above detection method has the risk of losing activity and introducing iatrogenic damage, which leads to limitations in practical applications.
而随着科技的进步和产业需求的提升,近年来基于体表的皮肤检测已开始追求实时的在体动态三维检测诊断模式,这种模式不仅能够获取人体皮肤组织的微米级3D形态结构、组成成分和分布信息,深入了解皮肤的生理和病理机制,而且还可以在线监测药物/化妆品活性成分在人体表皮的渗透、积聚和作用过程,进而通过皮肤组织的吸收机制和转运动力学阐明皮肤组织代谢和渗透途径的信息,开发和评价新型药物或化妆品。With the advancement of science and technology and the increase in industrial demand, in recent years, skin testing based on the body surface has begun to pursue real-time in-body dynamic three-dimensional detection and diagnosis mode. This mode can not only obtain the micron-level 3D morphological structure, composition and distribution information of human skin tissue, and deeply understand the physiological and pathological mechanisms of the skin, but also monitor the penetration, accumulation and action process of active ingredients of drugs/cosmetics in the human epidermis online, and then clarify the information of skin tissue metabolism and penetration pathways through the absorption mechanism and transport dynamics of skin tissue, and develop and evaluate new drugs or cosmetics.
然而迄今为止还没有一种仪器可以在综合人体皮肤危害性、成像深度、光学分辨率、成本等因素的考虑下实现皮肤微区结构的高分辨显微成像和分子结构分析的空间层析,即无法同时获得皮肤的结构信息及成分信息,在基于体表的皮肤影像成像领域,对于皮肤的在体三维结构检测,能够达到商业化应用阶段的设备和技术方法包括皮肤镜、OCT光学相干成像、共聚焦显微镜等,它们常用于提供皮肤状况生理参数的测量(例如颜色,红斑和色素沉着,硬结,皮脂和角质层脂质等)。由于单纯基于视觉检查的皮肤相关疾病的体内诊断往往具有挑战性,落脚点在皮肤组织内部成分分析的针对分子结构的检测则更多的是在将相应物质应用到皮肤上后,通过胶带剥离程序以及高效液相色谱实现定量应用的物质的提取和检测,但是这种方法对在体皮肤本身具有破坏性,因此实际应用中通常会受到限制,亟需非破坏性的,更全面的分析检测技术。However, there is no instrument that can achieve high-resolution microscopic imaging of skin microstructure and spatial tomography of molecular structure analysis under the consideration of factors such as human skin hazard, imaging depth, optical resolution, and cost. That is, it is impossible to obtain both the structural information and the composition information of the skin at the same time. In the field of skin imaging based on the body surface, the equipment and technical methods that can reach the commercial application stage for the in vivo three-dimensional structure detection of the skin include dermatoscopes, OCT optical coherence imaging, confocal microscopes, etc., which are often used to provide measurements of physiological parameters of skin conditions (such as color, erythema and pigmentation, nodules, sebum and stratum corneum lipids, etc.). Since the in vivo diagnosis of skin-related diseases based solely on visual inspection is often challenging, the detection of molecular structure based on the analysis of the internal components of skin tissue is more about applying the corresponding substances to the skin, and then extracting and detecting the substances for quantitative application through tape stripping procedures and high-performance liquid chromatography. However, this method is destructive to the in vivo skin itself, so it is usually limited in practical applications. Non-destructive and more comprehensive analytical detection technology is urgently needed.
针对上述问题,请参阅图1,本申请提供了一种在体皮肤光学检测装置10,上述在体皮肤光学检测装置10适用于对皮肤进行实时检测,进而获取待测皮肤目标区域20的表皮原始图像、三维结构信息及三维成分信息,可以理解的是,上述待测皮肤可以为在体皮肤,也可以为皮肤切片。In response to the above problems, please refer to Figure 1. The present application provides an in vivo skin optical detection device 10. The above-mentioned in vivo skin optical detection device 10 is suitable for real-time detection of the skin, and then obtaining the original image of the epidermis, three-dimensional structure information and three-dimensional composition information of the target area 20 of the skin to be tested. It can be understood that the above-mentioned skin to be tested can be in vivo skin or a skin slice.
请一并参阅图1至图6,在本实施例中,上述在体皮肤光学检测装置10包括表皮成像模组100、共聚焦显微模组200及拉曼散射模组300,表皮成像模组100、共聚焦显微模组200以及拉曼散射模组300共用部分光路结构,其中,表皮成像模组100用于获取待测皮肤目标区域20的表皮原始图像,共聚焦显微模组200用于获取待测皮肤目标区域20的三维结构信息(即图5所示),拉曼散射模组300用于获取待测皮肤目标区域的三维成分信息(即图6所示)。Please refer to Figures 1 to 6 together. In this embodiment, the above-mentioned in vivo skin optical detection device 10 includes an epidermal imaging module 100, a confocal microscopy module 200 and a Raman scattering module 300. The epidermal imaging module 100, the confocal microscopy module 200 and the Raman scattering module 300 share part of the optical path structure, wherein the epidermal imaging module 100 is used to obtain the original image of the epidermis of the target skin area 20 to be measured, the confocal microscopy module 200 is used to obtain the three-dimensional structural information of the target skin area 20 to be measured (i.e., as shown in Figure 5), and the Raman scattering module 300 is used to obtain the three-dimensional composition information of the target skin area to be measured (i.e., as shown in Figure 6).
本申请提供的在体皮肤光学检测装置10的有益效果在于,与现有技术相比,上述在体皮肤光学检测装置10通过表皮成像模组100、共聚焦显微模组200及拉曼散射模组300协同配合即实现对皮肤三维结构信息及三维成分信息的非侵入式检测,避免进行皮肤活体切片存在的失去活性以及引入医源性损伤的风险。The beneficial effect of the in vivo skin optical detection device 10 provided in the present application is that, compared with the prior art, the above-mentioned in vivo skin optical detection device 10 realizes non-invasive detection of the three-dimensional structural information and three-dimensional composition information of the skin through the coordinated cooperation of the epidermal imaging module 100, the confocal microscopy module 200 and the Raman scattering module 300, thereby avoiding the risk of loss of activity and introduction of iatrogenic damage in live skin sections.
请参阅图2,在本实施例中,上述表皮成像模组100包括科勒照明模块110,第一分光棱镜120、物镜模块130、扫描透镜-管镜镜组140、第一透镜150及第一成像模块160,其中,科勒照明模块110用于发射均匀的照明光线,扫描透镜-管镜镜组140由一个或多个扫描透镜(图未标示),及一个或多个管镜(图未标示)构成,进而用于放大物像,第一成像模块160为CCD或CMOS光学传感器。Please refer to Figure 2. In this embodiment, the above-mentioned epidermal imaging module 100 includes a Kohler illumination module 110, a first beam splitter prism 120, an objective lens module 130, a scanning lens-tube lens assembly 140, a first lens 150 and a first imaging module 160, wherein the Kohler illumination module 110 is used to emit uniform illumination light, the scanning lens-tube lens assembly 140 is composed of one or more scanning lenses (not shown in the figure) and one or more tube lenses (not shown in the figure), and is further used to magnify the object image, and the first imaging module 160 is a CCD or CMOS optical sensor.
进一步地,在本实施例中,上述照明光线依次经由第一分光棱镜120反射、物镜模块130聚焦后入射至待测皮肤目标区域20并生成反射光线,反射光线依次经由物镜模块130透射、第一分光棱镜120透射、扫描透镜-管镜镜组140透射、第一透镜150聚焦后入射至第一成像模块160生成待测皮肤目标区域20的表皮原始图像。Furthermore, in the present embodiment, the illumination light is sequentially reflected by the first beam splitter prism 120, focused by the objective lens module 130, and then incident on the target skin area 20 to be measured to generate reflected light; the reflected light is sequentially transmitted by the objective lens module 130, the first beam splitter prism 120, the scanning lens-tube lens assembly 140, and focused by the first lens 150, and then incident on the first imaging module 160 to generate an original image of the epidermis of the target skin area 20 to be measured.
进一步地,在本实施例中,上述物镜模块130包括固定镜筒132、物镜主体134及蓝宝石透光镜片136,其中,固定镜筒132两端开口,蓝宝石透光镜片136封闭于固定镜筒132用于朝向待测皮肤目标区域20的一端的开口处,且物镜主体134沿固定镜筒132轴向活动设置于固定镜筒132内,如此通过调节物镜主体134位置即可以适应性调节物镜主体134于待测皮肤目标区域20的对焦深度,并且,在检测过程中,待测皮肤目标区域20贴附于蓝宝石透光镜片136背向于物镜主体134的一侧,固定镜筒132随即隔绝环境光线照射在待测皮肤目标区域20上。Furthermore, in the present embodiment, the objective lens module 130 includes a fixed lens barrel 132, an objective lens body 134 and a sapphire light-transmitting lens 136, wherein both ends of the fixed lens barrel 132 are opened, the sapphire light-transmitting lens 136 is sealed in the opening of the fixed lens barrel 132 at one end facing the target skin area 20 to be measured, and the objective lens body 134 is movably arranged in the fixed lens barrel 132 along the axial direction of the fixed lens barrel 132, so that the focusing depth of the objective lens body 134 on the target skin area 20 to be measured can be adaptively adjusted by adjusting the position of the objective lens body 134, and, during the detection process, the target skin area 20 to be measured is attached to the side of the sapphire light-transmitting lens 136 facing away from the objective lens body 134, and the fixed lens barrel 132 is immediately isolated from ambient light and irradiated on the target skin area 20 to be measured.
请参阅图2,在本实施例中,上述照明光线相应依次经由第一分光棱镜120反射、物镜主体134聚焦、蓝宝石透光镜片136透射后入射至待测皮肤目标区域20并生成反射光线,反射光线依次经由蓝宝石透光镜片136透射、物镜主体134透射、第一分光棱镜透射120、扫描透镜-管镜镜组140透射、第一透镜150聚焦后入射至第一成像模块160生成待测皮肤目标区域20的表皮原始图像。Please refer to Figure 2. In this embodiment, the above-mentioned illumination light is respectively reflected by the first beam splitter prism 120, focused by the objective lens body 134, and transmitted by the sapphire transparent lens 136, and then incident on the target skin area 20 to be measured and generates reflected light. The reflected light is sequentially transmitted by the sapphire transparent lens 136, the objective lens body 134, the first beam splitter prism 120, the scanning lens-tube lens group 140, and focused by the first lens 150, and then incident on the first imaging module 160 to generate an original image of the epidermis of the target skin area 20 to be measured.
请参阅图2和图3,在本实施例中,上述共聚焦显微模组200包括激光光源模块210、中性密度滤光片220、第二透镜230、第一共焦针孔结构240、第三透镜250、偏振分光棱镜260、扫描振镜270、第二分光棱镜280、四分之一波片290、第四透镜292、第二共焦针孔结构294、及第二成像模块296,且扫描透镜-管镜镜组140构成4f光学系统,其中,激光光源模块210用于发射波长为810-850nm的准直激发光线,中性密度滤光片220用于控制激发光线的光照强度,扫描透镜-管镜镜组140构成的4f光学系统用于保障扫描振镜270扫描过程中,扫描振镜270处于不同角度时反射的光斑质量一致,第二成像模块296为APD光学传感器。Please refer to Figures 2 and 3. In this embodiment, the above-mentioned confocal microscopy module 200 includes a laser light source module 210, a neutral density filter 220, a second lens 230, a first confocal pinhole structure 240, a third lens 250, a polarization beam splitter prism 260, a scanning galvanometer 270, a second beam splitter prism 280, a quarter-wave plate 290, a fourth lens 292, a second confocal pinhole structure 294, and a second imaging module 296, and the scanning lens-tube lens group 140 constitutes a 4f optical system, wherein the laser light source module 210 is used to emit collimated excitation light with a wavelength of 810-850nm, the neutral density filter 220 is used to control the light intensity of the excitation light, and the 4f optical system constituted by the scanning lens-tube lens group 140 is used to ensure that during the scanning process of the scanning galvanometer 270, the quality of the light spot reflected by the scanning galvanometer 270 is consistent when the scanning galvanometer 270 is at different angles, and the second imaging module 296 is an APD optical sensor.
进一步地,在本实施例中,上述激发光线依次经由中性密度滤光片220滤光、第二透镜230聚焦、第一共焦针孔结构240滤光、第三透镜250准直、偏振分光棱镜260垂直偏振、扫描振镜270反射、第二分光棱镜280透射、扫描透镜-管镜镜组140透射、四分之一波片290偏振、第一分光棱镜120透射、物镜主体134聚焦、蓝宝石透光镜片136透射后入射至待测皮肤目标区域20生成散射光线,散射光线依次经由蓝宝石透光镜片136透射,物镜主体134透射、第一分光棱镜120透射、四分之一波片290偏振、扫描透镜-管镜镜组140透射,第二分光棱镜280透射、扫描振镜270反射、偏振分光棱镜260透射、第四透镜292聚焦、第二共焦针孔结构294滤光后入射至第二成像模块296生成待测皮肤目标区域20的三维结构信息。Further, in this embodiment, the excitation light is sequentially filtered by the neutral density filter 220, focused by the second lens 230, filtered by the first confocal pinhole structure 240, collimated by the third lens 250, vertically polarized by the polarization beam splitter prism 260, reflected by the scanning galvanometer 270, transmitted by the second beam splitter prism 280, transmitted by the scanning lens-tube lens assembly 140, polarized by the quarter wave plate 290, transmitted by the first beam splitter prism 120, focused by the objective lens body 134, and transmitted by the sapphire light-transmitting lens 136 before being incident on the skin to be measured. The skin target area 20 generates scattered light, which is sequentially transmitted through the sapphire transparent lens 136, the objective lens body 134, the first beam splitter prism 120, the quarter wave plate 290 polarization, the scanning lens-tube lens assembly 140, the second beam splitter prism 280, the scanning galvanometer 270, the polarization beam splitter prism 260, the fourth lens 292 focusing, the second confocal pinhole structure 294 filtering, and then incident on the second imaging module 296 to generate three-dimensional structural information of the skin target area 20 to be measured.
请参阅图2,在本实施例中,上述照明光线相应依次经由第一分光棱镜120反射、物镜主体134聚焦、蓝宝石透光镜片136透射后入射至待测皮肤目标区域20,反射光线依次经由蓝宝石透光镜片136透射,物镜主体134透射、第一分光棱镜120透射,四分之一波片290偏振、扫描透镜-管镜镜组140透射,第二分光棱镜280反射、第一透镜150聚焦后入射至第一成像模块160生成待测皮肤目标区域20的表皮原始图像。Please refer to Figure 2. In this embodiment, the above-mentioned illumination light is respectively reflected by the first beam splitter prism 120, focused by the objective lens body 134, and transmitted by the sapphire transparent lens 136 before being incident on the target skin area 20 to be measured. The reflected light is sequentially transmitted by the sapphire transparent lens 136, transmitted by the objective lens body 134, transmitted by the first beam splitter prism 120, polarized by the quarter wave plate 290, transmitted by the scanning lens-tube lens group 140, reflected by the second beam splitter prism 280, and focused by the first lens 150 before being incident on the first imaging module 160 to generate an original image of the epidermis of the target skin area 20 to be measured.
请参阅图4,在本实施例中,上述Please refer to FIG. 4. In this embodiment, the above
激发光线的波长为830nm,拉曼散射模组300包括第三分光棱镜310、长通滤光片320、第五透镜330、可调狭缝340、第一凹面反射镜350、光栅360、第二凹面反射镜370及第三成像模块380,其中,长通滤光片320的中心波长与激光光源模块210发出的激发光线的波长一致,即830nm,进而用于过滤激光光源模块210发出的激发光线以及瑞利散射光,保留波长大于原激光波长的斯托克斯拉曼散射光,第三成像模块380为CCD光学传感器。The wavelength of the excitation light is 830nm. The Raman scattering module 300 includes a third beam splitter prism 310, a long-pass filter 320, a fifth lens 330, an adjustable slit 340, a first concave reflector 350, a grating 360, a second concave reflector 370 and a third imaging module 380. The central wavelength of the long-pass filter 320 is consistent with the wavelength of the excitation light emitted by the laser light source module 210, that is, 830nm, and is further used to filter the excitation light and Rayleigh scattered light emitted by the laser light source module 210, and retain the Stokes Raman scattered light with a wavelength greater than the original laser wavelength. The third imaging module 380 is a CCD optical sensor.
进一步地,在本实施例中,上述激发光线依次经由中性密度滤光片220滤光、第二透镜230聚焦、第一共焦针孔结构240滤光、第三透镜250准直、偏振分光棱镜260垂直偏振、第三分光棱镜310透射,扫描振镜270反射、第二分光棱镜280透射、扫描透镜-管镜镜组140透射、四分之一波片290偏振、第一分光棱镜120透射、物镜主体134聚焦、蓝宝石透光镜片136透射后入射至待测皮肤目标区域20并生成散射光线,散射光线依次经由蓝宝石透光镜片136透射,物镜主体134透射、第一分光棱镜120透射、四分之一波片290偏振、扫描透镜-管镜镜组140透射,第二分光棱镜280透射、扫描振镜270反射、第三分光棱镜310反射、长通滤光片320滤光、第五透镜330聚焦、可调狭缝340滤光、第一凹面反射镜350反射、光栅360衍射、第二凹面反射镜370反射后入射至第三成像模块380生成待测皮肤目标区域20的三维成分信息。Further, in the present embodiment, the excitation light is sequentially filtered by the neutral density filter 220, focused by the second lens 230, filtered by the first confocal pinhole structure 240, collimated by the third lens 250, vertically polarized by the polarization beam splitter prism 260, transmitted by the third beam splitter prism 310, reflected by the scanning galvanometer 270, transmitted by the second beam splitter prism 280, transmitted by the scanning lens-tube lens assembly 140, polarized by the quarter wave plate 290, transmitted by the first beam splitter prism 120, focused by the objective lens body 134, and transmitted by the sapphire light-transmitting lens 136, and then incident on the target skin area 20 to be measured and generates scattered light. The scattered light is sequentially transmitted through the sapphire light-transmitting lens 136, the objective lens body 134, the first beam splitter prism 120, the quarter-wave plate 290 for polarization, the scanning lens-tube lens assembly 140, the second beam splitter prism 280, the scanning galvanometer 270, the third beam splitter prism 310, the long-pass filter 320, the fifth lens 330 for focusing, the adjustable slit 340 for filtering, the first concave reflector 350 for reflection, the grating 360 for diffraction, and the second concave reflector 370 for reflection before entering the third imaging module 380 to generate three-dimensional composition information of the target skin area 20 to be measured.
请参阅图3,在本实施例中,上述激发光线相应依次经由中性密度滤光片220滤光、第二透镜230聚焦、第一共焦针孔结构240滤光、第三透镜250准直、偏振分光棱镜260垂直偏振、第三分光棱镜310透射、扫描振镜270反射、第二分光棱镜280透射、扫描透镜-管镜镜组140透射、四分之一波片290偏振、第一分光棱镜120透射、物镜主体134聚焦、蓝宝石透光镜片136透射后入射至待测皮肤目标区域20,散射光线依次经由蓝宝石透光镜片136透射,物镜主体134透射、第一分光棱镜120透射、四分之一波片290偏振、扫描透镜-管镜镜组140透射,第二分光棱镜280透射、扫描振镜270反射、第三分光棱镜310透射、偏振分光棱镜260透射、第四透镜292聚焦、第二共焦针孔结构294滤光后入射至第二成像模块296生成待测皮肤目标区域20的三维结构信息。Please refer to FIG. 3 . In the present embodiment, the excitation light is filtered by the neutral density filter 220, focused by the second lens 230, filtered by the first confocal pinhole structure 240, collimated by the third lens 250, vertically polarized by the polarization beam splitter 260, transmitted by the third beam splitter prism 310, reflected by the scanning galvanometer 270, transmitted by the second beam splitter prism 280, transmitted by the scanning lens-tube lens assembly 140, polarized by the quarter wave plate 290, transmitted by the first beam splitter prism 120, focused by the objective lens body 134, and incident by the sapphire light-transmitting lens 136. To the target skin area 20 to be measured, the scattered light is transmitted in sequence through the sapphire transparent lens 136, the objective lens body 134, the first beam splitter prism 120, the quarter wave plate 290 polarization, the scanning lens-tube lens assembly 140, the second beam splitter prism 280, the scanning galvanometer 270, the third beam splitter prism 310, the polarization beam splitter prism 260, the fourth lens 292 focuses, and the second confocal pinhole structure 294 filters the light before entering the second imaging module 296 to generate the three-dimensional structural information of the target skin area 20 to be measured.
请参阅图3,在本实施例中,上述在体皮肤光学检测装置10还包括光路调整模组400,光路调整模组400包括第一平面反射镜410及第二平面反射镜420,其中,激发光线经由第三透镜250准直后,再经由第一平面反射镜410垂直反射至偏振分光棱镜260,散射光线经由第四透镜292聚焦后,再经由第二平面反射镜420垂直反射至第二共焦针孔结构294,需要说明的是,第一平面反射镜410及第二平面反射镜420仅用于改变在体皮肤光学检测装置10中相应光路方向,进而便于在体皮肤光学检测装置10中相关光学元件的紧凑式布局,有效降低在体皮肤光学检测装置10的整体尺寸。Please refer to Figure 3. In this embodiment, the above-mentioned in vivo skin optical detection device 10 also includes an optical path adjustment module 400, and the optical path adjustment module 400 includes a first plane reflector 410 and a second plane reflector 420, wherein the excitation light is collimated by the third lens 250, and then vertically reflected to the polarization splitter prism 260 by the first plane reflector 410, and the scattered light is focused by the fourth lens 292, and then vertically reflected to the second confocal pinhole structure 294 by the second plane reflector 420. It should be noted that the first plane reflector 410 and the second plane reflector 420 are only used to change the corresponding light path direction in the in vivo skin optical detection device 10, thereby facilitating the compact layout of related optical elements in the in vivo skin optical detection device 10, and effectively reducing the overall size of the in vivo skin optical detection device 10.
可以看出,上述在体皮肤光学检测装置10中表皮成像模组100、共聚焦显微模组200及拉曼散射模组300可以同步获取待测皮肤目标区域20的表皮原始图像、三维结构信息及三维成分信息,并且,表皮成像模组100、共聚焦显微模组200及拉曼散射模组300实现了部分光路以及部分光学元件复用,有效降低在体皮肤光学检测装置10的整体尺寸以及搭设成本。It can be seen that the epidermal imaging module 100, the confocal microscopy module 200 and the Raman scattering module 300 in the above-mentioned in vivo skin optical detection device 10 can synchronously obtain the original image of the epidermis, the three-dimensional structure information and the three-dimensional composition information of the target skin area 20 to be tested, and the epidermal imaging module 100, the confocal microscopy module 200 and the Raman scattering module 300 realize the reuse of part of the optical path and part of the optical elements, which effectively reduces the overall size and installation cost of the in vivo skin optical detection device 10.
进一步地,在本实施例中,上述在体皮肤光学检测装置10还包括三轴运动模块(图未示意)及固定平台(图未示意),其中,三轴运动模块驱动连接固定平台,如此,在对在体皮肤的检测过程中,可以将具有待测皮肤目标区域20的肢体放置于固定平台,也可以将具有待测皮肤目标区域20皮肤切片放置于固定平台,三轴运动模块随即驱动固定平台位移,使得物镜主体134能够在不同情况下均能准确对焦于待测皮肤目标区域20上。Furthermore, in the present embodiment, the above-mentioned in vivo skin optical detection device 10 also includes a three-axis motion module (not shown in the figure) and a fixed platform (not shown in the figure), wherein the three-axis motion module drives the connection to the fixed platform. Thus, during the detection of the in vivo skin, the limb having the target skin area 20 to be tested can be placed on the fixed platform, or the skin slice having the target skin area 20 to be tested can be placed on the fixed platform. The three-axis motion module then drives the fixed platform to move, so that the objective lens body 134 can be accurately focused on the target skin area 20 to be tested under different circumstances.
以上所述仅为本申请的较佳实施例而已,并不用以限制本申请,凡在本申请的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本申请的保护范围之内。The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.
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