单分子免疫检测系统的光学系统设计  

Optical system design of single molecule immune detection system

作　　者：范学仕 张薇[1] 江奔 韦晓孝 FAN Xueshi;ZHANG Wei;JIANG Ben;WEI Xiaoxiao(School of Optical-Electrical and Computer Enginnering,University of Shanghai for Science and Technology,Shanghai 200093,China)

机构地区：[1]上海理工大学光电信息与计算机工程学院,上海200093

出　　处：《光学技术》2023年第4期497-501,512,共6页Optical Technique

基　　金：国家重点研发计划资助(2022YFF0607705)。

摘　　要：单分子免疫检测,是指将免疫复合物限制在极小的体积内,对产生的信号进行计数,是一种“数字化”的免疫检测技术。单分子免疫检测仪的核心类似于一个荧光显微系统,但普通的荧光显微镜结构复杂,且与生物芯片规格无法匹配,不能很好地满足检测需求。针对自行研制的生物芯片规格,合计了一套高性能的单分子免疫检测光学系统。根据设计要求,确定了合适的初始结构;在荧光显微系统原理和像差分析理论的基础上,使用光学设计软件Zemax对系统进行反复优化设计;设计出了满足单分子免疫检测成像要求的光学系统。系统的成像部分由15片折射透镜组成,工作距离为4mm,放大倍率为-4.52,调制传递函数值在奈奎斯特频率73lp/mm处均大于0.44,畸变为0.8%,照明部分采用柯勒照明方式,在整个视场范围内,物面上的照度均匀度达到97%。整个系统采用国产常规玻璃,有利于加工和降低成本。经优化后的高分辨率荧光显微系统结合当前发展成熟的全自动化检测技术,可以极大提高单分子免疫检测的检测灵敏度和准确率。Single molecule immune detection refers to limiting immune complexes to a very small volume and counting the generated signals.It is a "digital" immune detection technology.The core of the single molecule immune detector is similar to a fluorescence microscope system,but the common fluorescence microscope has a complex structure and cannot match the specification of the biochip,which cannot meet the detection requirements well.A set of high performance optical system for single molecule immune detection is summarized according to the specification of biochip developed by ourselves.Firstly,the appropriate initial structure is determined according to the design requirements;Secondly,on the basis of fluorescence microscope system principle and aberration analysis theory,the optical design software Zemax is used to repeatedly optimize the system design;Finally,an optical system is designed to meet the imaging requirements of single molecule immune detection.The imaging part of the system consists of 15 pieces of refractive lenses,the working object distance is 4mm,the magnification is-4.52,the modulation transfer function values are greater than 0.44 at the Nyquist frequency of 73lp/mm,and the distortion is 0.8%,Kohler lighting mode is adopted for the lighting part,and the illuminance uniformity on the object surface reaches 97% in the whole field of view.The whole system adopts domestic conventional glass,which is conducive to processing and cost reduction.The optimized high resolution fluorescence microscopy system combined with the current fully automated detection technology can greatly improve the detection sensitivity and accuracy of single molecule immunoassay.

关 键 词：单分子免疫检测 生物芯片 光学设计 荧光成像系统 照明设计 高分辨率 

分 类 号：TP394.1[自动化与计算机技术—计算机应用技术] TH691.9[自动化与计算机技术—计算机科学与技术]