摘要
高端荧光、拉曼等生物医学检测需要超高透射、超锐截止滤光片,包括带通、单侧截止、多通带、陷波及分色等多种典型光谱类型。本文简要介绍了五种典型光谱滤光片的膜系设计方法,并以230层双侧锐截止带通典型膜系为代表,详细介绍了超多层薄膜的等离子反应溅射镀制工艺,多监控片膜厚控制及膜厚误差模拟仿真技术,超锐截止光谱表征技术及检测方法。最后给出研制的五种典型锐截止生物医学滤光片镀制结果(部分结果含增透):单面镀膜双侧锐截止带通滤光片的透射率大于95%,截止陡度优于1%;单面镀膜单侧锐截止滤光片峰值透射率大于95%,截止陡度优于0.7%;双面镀膜三通带锐截止滤光片平均透射率大于95%,截止陡度优于1%;陷波滤光片截止深度优于OD6,通带透射率大于90%;分色镜(45°入射)陡度优于1%,平均透射率大于95%。
The main studies in this paper were the research and development on the biomedical filters used in fluorescence and Raman detection.Biomedical Filters are key optical elements in Vitro Diagnostic(IVD)instruments in the field of biomedical&life science.These IVD instruments can detect and analyze human health status and diseases by detecting the absorption,scattering,and fluorescent radiation of light from human biological substances,pathogens,antibodies,etc.The detection result will assist doctors in disease diagnosis.The optical system determines the detection accuracy of IVD equipment.That why the performance of biomedical filters as the key elements in the optical system has a big effect on the detection accuracy and reliability of medical detection instruments.Biomedical filters are mainly used in three kinds of optical detection methods of IVD instruments:absorbance detection,fluorescence detection and Raman detection.Biomedical filters used in fluorescence and Raman detection are required high transmittance and increase the cutoff steepness to 1%or even 0.5%ultra-sharp cutoff level.It was introduced for various biomedical filters with ultra-high transmission and ultra-sharp edge manufactured based on Plasma Assisted Reactive Magnetron Sputtering(PARMS)coating technology.The typical spectral requirements of biomedical filters for fluorescence and Raman spectroscopy include bandpass(with sharp steepness on both sides),unilateral cut-off(long pass or short pass),notch filter,dichroic beam-splitter(incidence angle is 45°),and multiple typical spectra such as multi-bands filter which with one or more of the above spectral characteristics.Based on hard oxide materials such as Nb2O5,Ta2O5,Al2O3 and SiO2,five kinds of ultra-sharp cut-off filters were briefly introduced including their design methods.The basic design results were described.A long pass film system superimposed a short pass film could be used to design the bandpass filter.A multi-cavity bandpass film system as the initial film system could be also selected to design the bandpass filter.In this case,the difficulty point is how to use fewer layers to achieve a wide and deep cutoff.To research and develop edge filters,(HL)^n high and low refractive index cycle as the basic structure is mostly adopted.In this case,the difficulty is how to suppress the passband ripple when the superposition order is high.The rugate theory was applied to design an 808 nm edge filter to achieve the max design cut-off depth OD8.Fabry–Pérot cavity structure was used design a dichroic mirror.A low polarization separation and high steepness were achieved.A steepness below 1%was realized.Multi-pass band filters and dichroic mirrors are widely used in digital Polymerase Chain Reaction(PCR),genetic testing etc.Several of multi-pass band film system design methods were described.Some typical examples such as the design curve of three-pass band filters and three-pass band dichroic mirrors were provided in this paper.A typical bandpass biomedical filter BP660/12 nm with 230 layers was shown as an example.It was introduced that the manufacturing technology,optical thickness control technology,film thickness error simulation technology,ultra-sharp cutoff spectral characterization and detection method etc.PARMS was used to manufacture the biomedical filters.Direct optical control with multiple monitoring films was adopted.The membrane monitoring scheme was optimized through computer simulation.A super multilayer film was realized.The simulation error of the coating process was less than 0.15%.In the aspect of spectral characterization,the definition of cutoff steepness of biomedical filter bandpass,edge filter and dichroic mirror was emphasized.The influence of the test method on test results were specially emphasized.What's more,the different steepness test results obtained by different test methods for the same sample were given.Five typical spectra of biomedical filters in fluorescence and Raman use,with the coating and spectral detection results based on PARMS,were introduced at the end of the paper.Meanwhile,the influence from different steepness on the test range,test accuracy and signal strength of different test equipment was given.For the bandpass filter,the average transmittance of the band-pass filter was greater than 95%.The steepness was better than 1%.The signal-to-noise ratio of the PCR system was increased 20%on average by using the ultra-sharp edge filter.For the long-pass Raman filter,the cut-off steepness reached 0.67%.Low wavenumber measurement such as 100 cm^(-1)could be realized at 633nm.For the triple band filter,the transmittance was greater than 90%,the steepness was less than 1.5%.For 280-layer notch filter,the cut-off depth was OD6,which is 2 orders of magnitude lower than the designed value affected by the spectrophotometer.For the dichroic mirror,the polarization separation was less than 3 nm at 50%peak transmittance with angle of incidence of 45°.The receiving energy can be increased by 10%~30%depending on different fluorescent dyes.
作者
阴晓俊
王瑞生
赵帅锋
任少鹏
高鹏
费书国
YIN Xiaojun;WANG Ruisheng;ZHAO Shuaifeng;REN Shaopeng;GAO Peng;FEI Shuguo(HB Optical,SAIS CO.,LTD,Shenyang 110043,China;National Engineering Research Center of Transducer,Shenyang 110043,China)
出处
《光子学报》
EI
CAS
CSCD
北大核心
2022年第9期20-31,共12页
Acta Photonica Sinica
基金
科技部创新方法专项(No.2020IM010400)。
关键词
生物医学
滤光片
超多层薄膜
荧光
拉曼
等离子反应磁控溅射
Biomedical science
Filter
Super multilayer films
Fluorescence
Raman
Plasma assisted reactive magnetron sputtering