【作者】 王晓；

【导师】 张伟华； 张利剑；

【作者基本信息】 南京大学 ， 光学工程（专业学位）， 2021， 硕士

【摘要】 近年来随着社会对公共卫生与健康的关注,人们对低成本小型家用诊疗装置的需求迅速增加,在此趋势下研究人员发展了各类基于电化学、微机电诊断装置,但在生化诊断中常用的光学检测设备,特别是显微设备由于其体积庞大、价格昂贵在定量光学设备却仍在市场上缺失。因此,如何改善传统显微镜,将其体积减小、成本减少和功能丰富变得尤为重要。如今,随着物联网产业的高速发展,基于各种物联网设备的生物医疗检测技术取得的长足的进步。同时,芯片和高像素的成像传感器价格变得越来越低,网络传输速度越来越快,精密光学镜头越来越便宜。因此,本文介绍了一款基于物联网的智能数字光学显微系统,可以实现智能、便捷、高性能、低成本的定量生化检测。该数字光学显微系统主要分为硬件装置和软件设计两个方面,其中,硬件装置又分为光学系统和电子硬件控制系统。对于光学系统,经过光路设计,采用大焦距镜头当作无限校准的筒透镜,超小焦距无畸变镜头当作物镜,两者结合可放大显微物体并成像在图像传感器上,同时采用分光镜和两个光源,可以在明场条件下对样品进行透射式照明成像和反射式照明成像。整个系统经过软件设计后由3D打印完成,兼顾了精度的同时有效的降低了硬件成本。对于电子硬件方面,采用树莓派作为该显微装置的控制中心,使用AD/DA转换模块、电压跟随器亚微米精度控制控制载有小焦距物镜的音圈马达上下移动,以实现对焦功能。另外,接入两台步进电机滑台模组搭建二维方向的位移台,并结合树莓派步进电机驱动板实现亚微米精度控制载物台运动,使得显微镜可以20mm×20mm的范围内扫描样品。结合上述自动化硬件,我们设计了通用、智能的软件系统,可利用包括手机、平板电脑、笔记本电脑等各类设备直接链接并控制该显微系统,实现快速的自动对焦,自动的照明方式切换,以及样本的精确位移与扫描。具体的,我们选择在树莓派上进行后端开发和前端开发,使用Python语言编写后端程序,利用实施的图像检测算法实施对样品进行跟踪对焦,有效解决了小型显微镜易受振动影响的问题。前端采用HTML、CSS和JavaScript进行用户交互界面的设计,可以使用户通过手机、电脑等个人电子设备终端打开网页可以实时观察和操控系统等功能。当前该设备的主要性能可以达到或接近科研级显微镜的水平,具备透射、反射式等照明功能,具有600μm×450μm的视场范围,分辨率达微米级别,整体放大倍数高达2000×,同时,该系统可通过使用自动图像拼接算法实现厘米级样品的高清晰全貌图,并可利用人工智能算法对各类组织、细胞进行分析。结合该系统低成本、自动易用的特性,我们希望未来该系统能够被应用于快速的诊断与病理分析,特别是为贫穷偏远地区提供低成本高质量的服务。更多还原

【Abstract】 Today,the demand for low-cost portable diagnostic devices has been increasing rapidly due to the public health issues.Under this trend,various types of diagnostic devices were developed using electrochemical or MEM techniques.However,as one of the most commonly used diagnostic tools,quantitative optical inspection equipment,especially optical microscope,is still missing in the market due to its large volume and high price.Therefore,how to improve the traditional microscope,reduce its size,cost and rich function becomes particularly important.Interestingly,with the rapid development of the Internet of Things(Io T)industry,the smart Io T based diagnostic tools have made great progress in the last decade.Particularly,the price of image sensors and microcontroller has dropped drastically,network transmission speed becomes fast enough for real-time operations,and high quality optical lenses below 100 RMB become available.Intrigued by these changes,we introduces an low-cost smart digital optical microscope system based on Io T framework,which can automatically perform various quantitative bioanalysis.The development of the digital optical microscope system can be divided into two parts,hardware device and software design.The hardware consists of an optical system and an electronic hardware control system.In the optical system,a low-cost smartphone lens and a long focus length CCTV camera lens are used as the objective and tube lens,respectively,giving a up to 20-fold optical magnification.Two LEDs are used for the reflection and transmission mode illuminations.The whole system was constructed using 3D printing technique.In the electronics part,a single board computer,namely Raspberry PI4 is selected for all the automation control tasks,including a voice coil motor for focusing of the objective,two step motors for sample movement and LEDs for illumination.The sample movement range reaches 20mm×20mm and the precision of the focus adjustment is at micrometer level.Along the automatic hardware,we designed a software system which can perform rapid autofocus,automatic switching of lighting mode,as well as accurate sample displacement and scanning.It allows us to conveniently link and control the system by various portable devices including mobile phones,tablets and laptops via Wi Fi.Both the back-end development and front-end development were carried out on the Raspberry Pi.In the back-end program,an image detection algorithm was developed to track and focus samples,and it solves the image stability issue faced by small microscopes.The front-end uses HTML,CSS and JavaScript to design the user interaction interface,which enables users to operate the microscope by simply opening a web page.Currently,the major specifications of the low-cost microscope are same or close to the level of the research microscopes,with its multiple illumination modes,2micrometer spatial resolution,2000 folds magnification,600×450 microns field of view,autofocus function and automatic stitching function.In combination with the low cost and ease of use of the system,we hope that in the future the system can be applied to field of clinical diagnosis and pathological analysis,providing low cost and high quality services in remote areas.更多还原